PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 9022714-4 1996 The deletion mutants lacking the carboxy-terminal 24 amino acids hPAH (Ser2-Gln428) and hPAH(Gly103-Gln428) formed catalytically active dimers, and incubation with L-Phe did not promote the formation of tetramers, a characteristic property of dimeric wt-hPAH. Phenylalanine 164-169 phenylalanine hydroxylase Homo sapiens 65-69 9022714-9 1996 The amino-terminal deletion mutants hPAH(Asp112-Lys452) and hPAH(Gly103-Gln428) revealed high specific activity, increased apparent affinity for L-Phe (S0.5 = 60 microM) and a tryptophan fluorescence emission spectrum similar to that of the L-Phe-activated wt-hPAH. Phenylalanine 145-150 phenylalanine hydroxylase Homo sapiens 36-40 9022714-9 1996 The amino-terminal deletion mutants hPAH(Asp112-Lys452) and hPAH(Gly103-Gln428) revealed high specific activity, increased apparent affinity for L-Phe (S0.5 = 60 microM) and a tryptophan fluorescence emission spectrum similar to that of the L-Phe-activated wt-hPAH. Phenylalanine 145-150 phenylalanine hydroxylase Homo sapiens 60-64 9022714-9 1996 The amino-terminal deletion mutants hPAH(Asp112-Lys452) and hPAH(Gly103-Gln428) revealed high specific activity, increased apparent affinity for L-Phe (S0.5 = 60 microM) and a tryptophan fluorescence emission spectrum similar to that of the L-Phe-activated wt-hPAH. Phenylalanine 145-150 phenylalanine hydroxylase Homo sapiens 60-64 9022714-9 1996 The amino-terminal deletion mutants hPAH(Asp112-Lys452) and hPAH(Gly103-Gln428) revealed high specific activity, increased apparent affinity for L-Phe (S0.5 = 60 microM) and a tryptophan fluorescence emission spectrum similar to that of the L-Phe-activated wt-hPAH. Phenylalanine 241-246 phenylalanine hydroxylase Homo sapiens 36-40 9022714-9 1996 The amino-terminal deletion mutants hPAH(Asp112-Lys452) and hPAH(Gly103-Gln428) revealed high specific activity, increased apparent affinity for L-Phe (S0.5 = 60 microM) and a tryptophan fluorescence emission spectrum similar to that of the L-Phe-activated wt-hPAH. Phenylalanine 241-246 phenylalanine hydroxylase Homo sapiens 60-64 9022714-9 1996 The amino-terminal deletion mutants hPAH(Asp112-Lys452) and hPAH(Gly103-Gln428) revealed high specific activity, increased apparent affinity for L-Phe (S0.5 = 60 microM) and a tryptophan fluorescence emission spectrum similar to that of the L-Phe-activated wt-hPAH. Phenylalanine 241-246 phenylalanine hydroxylase Homo sapiens 60-64 9022714-11 1996 Our results are compatible with a model in which incubation of wt-hPAH with L-Phe induces both a conformational change (with cooperativity in the tetrameric enzyme) which relieves the inhibition imposed by the amino-terminal domain to the high-affinity binding of L-Phe, and an additional activation, as observed for the truncated forms lacking the amino-terminal. Phenylalanine 76-81 phenylalanine hydroxylase Homo sapiens 66-70 9022714-11 1996 Our results are compatible with a model in which incubation of wt-hPAH with L-Phe induces both a conformational change (with cooperativity in the tetrameric enzyme) which relieves the inhibition imposed by the amino-terminal domain to the high-affinity binding of L-Phe, and an additional activation, as observed for the truncated forms lacking the amino-terminal. Phenylalanine 264-269 phenylalanine hydroxylase Homo sapiens 66-70 9022714-4 1996 The deletion mutants lacking the carboxy-terminal 24 amino acids hPAH (Ser2-Gln428) and hPAH(Gly103-Gln428) formed catalytically active dimers, and incubation with L-Phe did not promote the formation of tetramers, a characteristic property of dimeric wt-hPAH. Phenylalanine 164-169 phenylalanine hydroxylase Homo sapiens 88-92 9022714-4 1996 The deletion mutants lacking the carboxy-terminal 24 amino acids hPAH (Ser2-Gln428) and hPAH(Gly103-Gln428) formed catalytically active dimers, and incubation with L-Phe did not promote the formation of tetramers, a characteristic property of dimeric wt-hPAH. Phenylalanine 164-169 phenylalanine hydroxylase Homo sapiens 88-92 9022714-6 1996 The deletion mutants hPAH(Asp112-Lys452), hPAH(Ser2-Gln428) and hPAH(Gly103-Gln428) were all activated by prior incubation with L-Phe, but did not reveal any positive cooperativity of substrate binding (h = 1.0). Phenylalanine 128-133 phenylalanine hydroxylase Homo sapiens 21-25 9022714-6 1996 The deletion mutants hPAH(Asp112-Lys452), hPAH(Ser2-Gln428) and hPAH(Gly103-Gln428) were all activated by prior incubation with L-Phe, but did not reveal any positive cooperativity of substrate binding (h = 1.0). Phenylalanine 128-133 phenylalanine hydroxylase Homo sapiens 42-46 9022714-6 1996 The deletion mutants hPAH(Asp112-Lys452), hPAH(Ser2-Gln428) and hPAH(Gly103-Gln428) were all activated by prior incubation with L-Phe, but did not reveal any positive cooperativity of substrate binding (h = 1.0). Phenylalanine 128-133 phenylalanine hydroxylase Homo sapiens 42-46 8921003-1 1996 Mammalian phenylalanine hydroxylase (PAH) catalyses the conversion of L-phenylalanine to L-tyrosine in the presence of dioxygen and tetrahydrobiopterin; it is a highly regulated enzyme. Phenylalanine 70-85 phenylalanine hydroxylase Homo sapiens 37-40 8921003-1 1996 Mammalian phenylalanine hydroxylase (PAH) catalyses the conversion of L-phenylalanine to L-tyrosine in the presence of dioxygen and tetrahydrobiopterin; it is a highly regulated enzyme. Phenylalanine 70-85 phenylalanine hydroxylase Homo sapiens 10-35 8946176-1 1996 Phenylalanine hydroxylase (PAH) is the enzyme which converts phenylalanine into tyrosine. Phenylalanine 61-74 phenylalanine hydroxylase Homo sapiens 0-25 8828600-4 1996 This paper gives a summary of the effect of each type of mutation on PAH activity and illustrates how the combination of mutations (the genotype) is associated with the Phe tolerance (the metabolic phenotype). Phenylalanine 169-172 phenylalanine hydroxylase Homo sapiens 69-72 8632937-9 1996 Strong correlations were observed between the level of PAH activity predicted from the genotype, when known from previous in vitro expression studies of the mutant proteins, and pretreatment serum PHE levels (r = .841) or clinical severity (Kendall rank-order correlation coefficient, .936). Phenylalanine 197-200 phenylalanine hydroxylase Homo sapiens 55-58 8573072-4 1996 The rate of phosphorylation of human phenylalanine hydroxylase was inhibited about 40% by the cofactor tetrahydrobiopterin, and this inhibition was completely prevented by the simultaneous presence of L-phenylalanine (i.e. at turnover conditions). Phenylalanine 201-216 phenylalanine hydroxylase Homo sapiens 37-62 8573072-6 1996 Pre-incubation with L-Phe increased the specific activity of phenylalanine hydroxylase 2- to 4-fold, L-Phe acting with positive cooperativity. Phenylalanine 20-25 phenylalanine hydroxylase Homo sapiens 61-86 8573072-6 1996 Pre-incubation with L-Phe increased the specific activity of phenylalanine hydroxylase 2- to 4-fold, L-Phe acting with positive cooperativity. Phenylalanine 101-106 phenylalanine hydroxylase Homo sapiens 61-86 8946176-1 1996 Phenylalanine hydroxylase (PAH) is the enzyme which converts phenylalanine into tyrosine. Phenylalanine 61-74 phenylalanine hydroxylase Homo sapiens 27-30 8892014-4 1996 We report two siblings of different sex and identical genotype at the PAH locus who demonstrate a difference in phenylalanine disposal. Phenylalanine 112-125 phenylalanine hydroxylase Homo sapiens 70-73 7547912-8 1995 After incubation with phenylalanine, the quantum yield of wild-type hPAH increases by 15%, and the emission maximum is shifted from 336.5 to 347 nm. Phenylalanine 22-35 phenylalanine hydroxylase Homo sapiens 68-72 7766948-4 1994 In contrast, infusion of a recombinant adenoviral vector expressing the human PAH cDNA into the portal circulation of PAH-deficient mice restores 10-80% of normal hepatic PAH activity and completely normalizes serum phenylalanine levels. Phenylalanine 216-229 phenylalanine hydroxylase Homo sapiens 78-81 7762520-1 1995 To assess the production of the nonessential amino acid tyrosine in preterm infants, we estimated the activity of phenylalanine hydroxylase (PAH) in three groups of infants by measuring the conversion of phenylalanine to tyrosine, using a model based on a primed constant 200-min intravenous infusion of [2H5]phenylalanine. Phenylalanine 114-127 phenylalanine hydroxylase Homo sapiens 141-144 7762520-9 1995 Provision of phenylalanine in the context of parenteral amino acid nutrition solution accelerated PAH conversion of phenylalanine to tyrosine, suggesting that the enzyme system is capable of responding normally to provision of substrate. Phenylalanine 13-26 phenylalanine hydroxylase Homo sapiens 98-101 7762520-9 1995 Provision of phenylalanine in the context of parenteral amino acid nutrition solution accelerated PAH conversion of phenylalanine to tyrosine, suggesting that the enzyme system is capable of responding normally to provision of substrate. Phenylalanine 116-129 phenylalanine hydroxylase Homo sapiens 98-101 7766948-4 1994 In contrast, infusion of a recombinant adenoviral vector expressing the human PAH cDNA into the portal circulation of PAH-deficient mice restores 10-80% of normal hepatic PAH activity and completely normalizes serum phenylalanine levels. Phenylalanine 216-229 phenylalanine hydroxylase Homo sapiens 118-121 1288453-11 1992 A mutation which changed the affinity of PAH for phenylalanine was associated with mild hyperphenylalaninemia. Phenylalanine 49-62 phenylalanine hydroxylase Homo sapiens 41-44 8444221-8 1993 There was a strong relationship between the average in vitro PAH activity of the two mutant enzymes and both the phenylalanine tolerance and the neonatal pretreatment serum phenylalanine concentration. Phenylalanine 113-126 phenylalanine hydroxylase Homo sapiens 61-64 8444221-8 1993 There was a strong relationship between the average in vitro PAH activity of the two mutant enzymes and both the phenylalanine tolerance and the neonatal pretreatment serum phenylalanine concentration. Phenylalanine 173-186 phenylalanine hydroxylase Homo sapiens 61-64 8132651-1 1994 Human phenylalanine hydroxylase (PAH) is specifically expressed in the liver to convert L-phenylalanine to L-tyrosine. Phenylalanine 88-103 phenylalanine hydroxylase Homo sapiens 6-31 8132651-1 1994 Human phenylalanine hydroxylase (PAH) is specifically expressed in the liver to convert L-phenylalanine to L-tyrosine. Phenylalanine 88-103 phenylalanine hydroxylase Homo sapiens 33-36 7967476-1 1994 We examined whether the degree of residual activity from the mutant phenylalanine hydroxylase (PAH) allele affected phenylalanine metabolism in heterozygotes for phenylketonuria (PKU) or non-PKU hyperphenylalaninaemia (HPA). Phenylalanine 68-81 phenylalanine hydroxylase Homo sapiens 95-98 7967476-7 1994 Differences in the activities from the carried mutant PAH allele on phenylalanine metabolism in heterozygotes are, however, small compared to the activity from the normal PAH allele and are easily obscured by other factors leading to inter- or intra-individual variation in phenylalanine metabolism. Phenylalanine 68-81 phenylalanine hydroxylase Homo sapiens 54-57 7967476-7 1994 Differences in the activities from the carried mutant PAH allele on phenylalanine metabolism in heterozygotes are, however, small compared to the activity from the normal PAH allele and are easily obscured by other factors leading to inter- or intra-individual variation in phenylalanine metabolism. Phenylalanine 68-81 phenylalanine hydroxylase Homo sapiens 171-174 7967476-7 1994 Differences in the activities from the carried mutant PAH allele on phenylalanine metabolism in heterozygotes are, however, small compared to the activity from the normal PAH allele and are easily obscured by other factors leading to inter- or intra-individual variation in phenylalanine metabolism. Phenylalanine 274-287 phenylalanine hydroxylase Homo sapiens 54-57 7967476-7 1994 Differences in the activities from the carried mutant PAH allele on phenylalanine metabolism in heterozygotes are, however, small compared to the activity from the normal PAH allele and are easily obscured by other factors leading to inter- or intra-individual variation in phenylalanine metabolism. Phenylalanine 274-287 phenylalanine hydroxylase Homo sapiens 171-174 8352282-4 1993 Phenylalanine hydroxylase catalyzes a coupled reaction in which phenylalanine is converted to tyrosine and in which tetrahydrobiopterin is converted to the unstable carbinolamine, 4a-hydroxytetrahydrobiopterin. Phenylalanine 64-77 phenylalanine hydroxylase Homo sapiens 0-25 34952194-2 2022 PAH is an important metabolic enzyme of aromatic amino acids and the rate-limiting enzyme in the hydroxylation of amino acid phenylalanine to tyrosine. Phenylalanine 125-138 phenylalanine hydroxylase Homo sapiens 0-3 1867197-1 1991 Hyperphenylalaninemia (HPA) results from defective hydroxylation of phenylalanine in the liver, in most cases because of defective phenylalanine hydroxylase. Phenylalanine 5-18 phenylalanine hydroxylase Homo sapiens 131-156 2014036-9 1991 The predicted level of phenylalanine hydroxylase activity correlated strongly with the pretreatment serum level of phenylalanine (r = 0.91, P less than 0.001 in the Danish patients and r = 0.74, P less than 0.001 in the German patients), phenylalanine tolerance in the Danish patients (r = 0.84, P less than 0.001), and the serum phenylalanine level measured after standardized oral protein loading in the German patients (r = 0.84, P less than 0.001). Phenylalanine 115-128 phenylalanine hydroxylase Homo sapiens 23-48 2014036-9 1991 The predicted level of phenylalanine hydroxylase activity correlated strongly with the pretreatment serum level of phenylalanine (r = 0.91, P less than 0.001 in the Danish patients and r = 0.74, P less than 0.001 in the German patients), phenylalanine tolerance in the Danish patients (r = 0.84, P less than 0.001), and the serum phenylalanine level measured after standardized oral protein loading in the German patients (r = 0.84, P less than 0.001). Phenylalanine 115-128 phenylalanine hydroxylase Homo sapiens 23-48 2069475-1 1991 The occurrence of increased levels of blood phenylalanine after therapeutic administration of folate analogues has been occasionally reported and attributed to the inhibition of dihydropteridine reductase, an enzyme maintaining the cofactor of phenylalanine hydroxylase in its active tetrahydrogenated form (tetrahydrobiopterin). Phenylalanine 44-57 phenylalanine hydroxylase Homo sapiens 244-269 1671881-2 1991 The abolition of an invariant BamHI site located in the coding sequence of the PAH gene (exon 7) led to the recognition of two new point mutations at codon 272 and 273 (272gly----stop and 273ser----phe, respectively). Phenylalanine 198-201 phenylalanine hydroxylase Homo sapiens 79-82 1326329-1 1992 Human phenylalanine hydroxylase (PAH) is expressed in a liver-specific manner and catalyzes the enzymatic conversion of phenylalanine to tyrosine. Phenylalanine 6-19 phenylalanine hydroxylase Homo sapiens 33-36 1355046-3 1992 It has been shown that the 7-substituted isomers of biopterin and neopterin derive from L-tetrahydrobiopterin and D-tetrahydroneopterin and are formed during hydroxylation of phenylalanine to tyrosine with rat liver dehydratase-free phenylalanine hydroxylase. Phenylalanine 175-188 phenylalanine hydroxylase Homo sapiens 233-258 1944771-5 1991 Although essentially no hydrogen peroxide is formed during the fully coupled oxidation of tetrahydrobiopterin or 6-methyltetrahydropterin by phenylalanine hydroxylase when phenylalanine is the amino acid substrate, significant amounts of hydrogen peroxide are formed during the partially uncoupled oxidation of 6-methyltetrahydropterin when para-fluorophenylalanine or para-chlorophenylalanine are used in place of phenylalanine. Phenylalanine 172-185 phenylalanine hydroxylase Homo sapiens 141-166 1709636-3 1991 We report here a 3-base pair in-frame deletion of the PAH gene (delta 194) in a mild variant, with markedly reduced affinity of the enzyme for phenylalanine (Km = 160 nM), and we provide functional evidence for responsibility of the deletion in the mutant phenotype. Phenylalanine 143-156 phenylalanine hydroxylase Homo sapiens 54-57 2220810-4 1990 Haplotypes at the PAH locus were determined for 19 individuals with moderately elevated plasma phenylalanine and normal urinary neopterin/biopterin ratios. Phenylalanine 95-108 phenylalanine hydroxylase Homo sapiens 18-21 2220810-7 1990 Elevated plasma phenylalanine was seen to genetically segregate with specific PAH alleles in each family. Phenylalanine 16-29 phenylalanine hydroxylase Homo sapiens 78-81 2220810-9 1990 At theta = 0 this gives a probability of linkage between the PAH locus and the locus for moderate phenylalanine elevations that is approximately 3,600:1. Phenylalanine 98-111 phenylalanine hydroxylase Homo sapiens 61-64 33819046-1 2021 Phenylketonuria (PKU) is a disease of the catabolism of phenylalanine (Phe), caused by an impaired function of the enzyme phenylalanine hydroxylase. Phenylalanine 56-69 phenylalanine hydroxylase Homo sapiens 122-147 33819046-1 2021 Phenylketonuria (PKU) is a disease of the catabolism of phenylalanine (Phe), caused by an impaired function of the enzyme phenylalanine hydroxylase. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 122-147 34784942-2 2021 PAH impairment causes phenylalanine accumulation in the blood and brain, with a broad spectrum of pathophysiological and neurological consequences for patients. Phenylalanine 22-35 phenylalanine hydroxylase Homo sapiens 0-3 34819582-3 2021 A potentially one-time rAAV-based delivery of PAH gene into liver to convert Phe into tyrosine (Tyr), a normal way of Phe metabolism, has now also entered the clinic. Phenylalanine 77-80 phenylalanine hydroxylase Homo sapiens 46-49 34819582-3 2021 A potentially one-time rAAV-based delivery of PAH gene into liver to convert Phe into tyrosine (Tyr), a normal way of Phe metabolism, has now also entered the clinic. Phenylalanine 118-121 phenylalanine hydroxylase Homo sapiens 46-49 34900593-1 2021 Phenylketonuria (PKU) is an inborn error of metabolism caused by variants in the phenylalanine hydroxylase (PAH) gene and it is characterized by excessively high levels of phenylalanine in body fluids. Phenylalanine 172-185 phenylalanine hydroxylase Homo sapiens 81-106 34784942-1 2021 BACKGROUND: Phenylketonuria (PKU) is a rare inherited metabolic disorder caused by defects in the phenylalanine-hydroxylase gene (PAH), the enzyme catalyzing the conversion of phenylalanine to tyrosine. Phenylalanine 176-189 phenylalanine hydroxylase Homo sapiens 98-123 34784942-1 2021 BACKGROUND: Phenylketonuria (PKU) is a rare inherited metabolic disorder caused by defects in the phenylalanine-hydroxylase gene (PAH), the enzyme catalyzing the conversion of phenylalanine to tyrosine. Phenylalanine 176-189 phenylalanine hydroxylase Homo sapiens 130-133 34207146-1 2021 Human phenylalanine hydroxylase (PAH) is a metabolic enzyme involved in the catabolism of L-Phe in liver. Phenylalanine 90-95 phenylalanine hydroxylase Homo sapiens 6-31 34412683-1 2021 BACKGROUND: In classical phenylketonuria (PKU) phenylalanine (Phe) accumulates due to functional impairment of the enzyme phenylalanine hydroxylase caused by pathogenic variants in the PAH gene. Phenylalanine 47-60 phenylalanine hydroxylase Homo sapiens 122-147 34412683-1 2021 BACKGROUND: In classical phenylketonuria (PKU) phenylalanine (Phe) accumulates due to functional impairment of the enzyme phenylalanine hydroxylase caused by pathogenic variants in the PAH gene. Phenylalanine 47-60 phenylalanine hydroxylase Homo sapiens 185-188 34412683-1 2021 BACKGROUND: In classical phenylketonuria (PKU) phenylalanine (Phe) accumulates due to functional impairment of the enzyme phenylalanine hydroxylase caused by pathogenic variants in the PAH gene. Phenylalanine 62-65 phenylalanine hydroxylase Homo sapiens 122-147 34412683-1 2021 BACKGROUND: In classical phenylketonuria (PKU) phenylalanine (Phe) accumulates due to functional impairment of the enzyme phenylalanine hydroxylase caused by pathogenic variants in the PAH gene. Phenylalanine 62-65 phenylalanine hydroxylase Homo sapiens 185-188 34145024-9 2021 Among them the PKA targets phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine. Phenylalanine 87-100 phenylalanine hydroxylase Homo sapiens 27-52 34162223-12 2021 Observations from aged mice and human samples implicated age-related decline in hepatic Phe catabolism as a key driver of elevated plasma Phe levels and showed increased myocardial PAH-mediated Phe catabolism, a novel signature of cardiac aging. Phenylalanine 194-197 phenylalanine hydroxylase Homo sapiens 181-184 34162223-14 2021 They highlight Phe/PAH modulation as a potential therapeutic strategy for age-associated cardiac impairment. Phenylalanine 15-18 phenylalanine hydroxylase Homo sapiens 19-22 34207146-1 2021 Human phenylalanine hydroxylase (PAH) is a metabolic enzyme involved in the catabolism of L-Phe in liver. Phenylalanine 90-95 phenylalanine hydroxylase Homo sapiens 33-36 35449354-4 2022 However, recent evidence revealed that PAH tetramers exist as a mixture of resting state and activated state whose transition depends upon the phenylalanine concentration and certain PAH variants that fail to modulate the structural equilibrium are associated with PKU disease. Phenylalanine 143-156 phenylalanine hydroxylase Homo sapiens 39-42 35600090-2 2022 Without a functional copy of PAH, levels of Phe in the blood and tissues rise, resulting in potentially life-threatening damage to the central nervous system. Phenylalanine 44-47 phenylalanine hydroxylase Homo sapiens 29-32 35449354-20 2022 USP19 increases the enzymatic activity of PAH, thus maintaining normal Phe levels. Phenylalanine 71-74 phenylalanine hydroxylase Homo sapiens 42-45 35325557-1 2022 Phenylketonuria (PKU) is an autosomal recessive disease caused by variants in the gene that encodes phenylalanine hydroxylase (PAH), limiting the metabolism of phenylalanine (Phe). Phenylalanine 160-173 phenylalanine hydroxylase Homo sapiens 100-125 35325557-1 2022 Phenylketonuria (PKU) is an autosomal recessive disease caused by variants in the gene that encodes phenylalanine hydroxylase (PAH), limiting the metabolism of phenylalanine (Phe). Phenylalanine 160-173 phenylalanine hydroxylase Homo sapiens 127-130 35325557-1 2022 Phenylketonuria (PKU) is an autosomal recessive disease caused by variants in the gene that encodes phenylalanine hydroxylase (PAH), limiting the metabolism of phenylalanine (Phe). Phenylalanine 175-178 phenylalanine hydroxylase Homo sapiens 100-125 35325557-1 2022 Phenylketonuria (PKU) is an autosomal recessive disease caused by variants in the gene that encodes phenylalanine hydroxylase (PAH), limiting the metabolism of phenylalanine (Phe). Phenylalanine 175-178 phenylalanine hydroxylase Homo sapiens 127-130 35325557-2 2022 When PAH activity is absent or hindered, Phe is not converted to tyrosine, leading to an accumulation of Phe in the blood, which can cause serious neurological complications. Phenylalanine 41-44 phenylalanine hydroxylase Homo sapiens 5-8 35325557-2 2022 When PAH activity is absent or hindered, Phe is not converted to tyrosine, leading to an accumulation of Phe in the blood, which can cause serious neurological complications. Phenylalanine 105-108 phenylalanine hydroxylase Homo sapiens 5-8 3019383-5 1986 Oxygen consumption during PAH reduction by tetrahydropterin in the absence of phenylalanine but not in its presence explains the different reduction stoichiometries (tetrahydropterin:enzyme) that have been observed. Phenylalanine 78-91 phenylalanine hydroxylase Homo sapiens 26-29 35356682-6 2022 We show that intravenous infusion of LUNAR-hPAH mRNA can generate high levels of hPAH protein in hepatocytes and restore the Phe metabolism in the Pah enu2 mouse model. Phenylalanine 125-128 phenylalanine hydroxylase Homo sapiens 43-47 35082602-1 2021 Phenylketonuria is a recessive genetic disorder of amino-acid metabolism, where impaired phenylalanine hydroxylase function leads to the accumulation of neurotoxic phenylalanine levels in the brain. Phenylalanine 164-177 phenylalanine hydroxylase Homo sapiens 89-114 3186165-6 1988 Hence, the major part of phenylalanine oxidizing activity in the embryonic liver is related to the enzyme immunochemically identical with the PH of adult liver but differing from it in some structural and functional properties. Phenylalanine 25-38 phenylalanine hydroxylase Homo sapiens 142-144 3326734-1 1987 The phenylalanine-hydroxylating system consists of 3 essential components, phenylalanine hydroxylase (PAH), dihydropteridine reductase (DHPR) and the coenzyme, tetrahydrobiopterin (BH4). Phenylalanine 4-17 phenylalanine hydroxylase Homo sapiens 75-100 3326734-1 1987 The phenylalanine-hydroxylating system consists of 3 essential components, phenylalanine hydroxylase (PAH), dihydropteridine reductase (DHPR) and the coenzyme, tetrahydrobiopterin (BH4). Phenylalanine 4-17 phenylalanine hydroxylase Homo sapiens 102-105 3751555-7 1986 It seems likely that those of our patients who markedly increased their phenylalanine tolerance during childhood had a regulatory mutation of the phenylalanine hydroxylase system. Phenylalanine 72-85 phenylalanine hydroxylase Homo sapiens 146-171 6530447-4 1984 This methodology is used to study the electrochemistry of q-BH2 formed by oxidation of BH4 and in the hydroxylation of phenylalanine by phenylalanine hydroxylase. Phenylalanine 119-132 phenylalanine hydroxylase Homo sapiens 136-161 3994703-0 1985 Effects of phenylalanine on phenylalanine hydroxylase separation and stability. Phenylalanine 11-24 phenylalanine hydroxylase Homo sapiens 28-53 3930837-1 1985 The hepatic phenylalanine hydroxylating system consists of three essential components, phenylalanine hydroxylase, dihydropteridine reductase and the non-protein coenzyme, tetrahydrobiopterin. Phenylalanine 12-25 phenylalanine hydroxylase Homo sapiens 87-112 6803767-5 1981 The binding of PH alpha 1-1 antibody to phenylalanine hydroxylase is dependent on substrate phenylalanine, whereas the binding of the others is not influenced by phenylalanine. Phenylalanine 92-105 phenylalanine hydroxylase Homo sapiens 40-65 6495818-1 1984 The enzymic hydroxylation of phenylalanine by phenylalanine hydroxylase (E.C. Phenylalanine 29-42 phenylalanine hydroxylase Homo sapiens 46-71 6495818-6 1984 These findings suggest that the termination of phenylalanine hydroxylation in the absence of hydrogen peroxide removing reactions is probably due to destructive oxygen species generated at the active site iron of phenylalanine hydroxylase in the presence of H2O2 and the tetrahydropterin cofactor. Phenylalanine 47-60 phenylalanine hydroxylase Homo sapiens 213-238 6282659-1 1982 The site of oxygen binding during phenylalanine hydroxylase (PAH)-catalyzed turnover of phenylalanine to tyrosine has been tentatively identified as the 4a position of the tetrahydropterin cofactor, based on the spectral characteristics of an intermediate generated from both 6-methyltetrahydropterin and tetrahydrobiopterin during turnover. Phenylalanine 34-47 phenylalanine hydroxylase Homo sapiens 61-64 6489353-4 1984 Phenylalanine 4-monooxygenase was also a substrate for the cGMP-dependent protein kinase, but in this system phenylalanine stimulated the rate of phosphorylation to a similar extent as that observed in the reaction catalyzed by cAMP-dependent protein kinase. Phenylalanine 109-122 phenylalanine hydroxylase Homo sapiens 0-29 6698976-7 1984 Both phenylalanine and (6R)-tetrahydrobiopterin inhibit to a small extent the dephosphorylation of phosphorylated phenylalanine hydroxylase catalyzed by phosphoprotein phosphatase. Phenylalanine 5-18 phenylalanine hydroxylase Homo sapiens 114-139 7132735-15 1982 This supports the existence of some type of substance activation of the enzyme as reflected in the previously reported exponential relationship between phenylalanine concentration and phenylalanine hydroxylase activity in vitro. Phenylalanine 152-165 phenylalanine hydroxylase Homo sapiens 184-209 7132735-16 1982 The use of continuous simultaneous infusions of tracer amounts of stable isotope-labeled phenylalanine and tyrosine provides a direct means for studying physiological regulation of phenylalanine hydroxylase activity in vivo. Phenylalanine 89-102 phenylalanine hydroxylase Homo sapiens 181-206 221463-2 1979 The phenylalanine-dependent, phenylalanine hydroxylase-catalyzed reaction in the presence of the pyrimidine is largely, but not completely, uncoupled; the ratio of DPNH oxidized to tyrosine formed is about 20 to 1. Phenylalanine 4-17 phenylalanine hydroxylase Homo sapiens 29-54 511154-2 1979 Phenylalanine is converted to tyrosine by phenylalanine hydroxylase, which is located mainly in the liver. Phenylalanine 0-13 phenylalanine hydroxylase Homo sapiens 42-67 1160969-2 1975 In assays of the components of the phenylalanine hydroxylating system (open liver biopsy at 14 months), the activity of phenylalanine hydroxylase was 20 per cent of the average normal adult value. Phenylalanine 35-48 phenylalanine hydroxylase Homo sapiens 120-145 624182-1 1978 Consideration of the flow of phenylalanine within the body shows that classical phenylalanine load tests for assessing phenylalanine hydroxylase activity cannot usefully be replaced by tracer techniques. Phenylalanine 80-93 phenylalanine hydroxylase Homo sapiens 119-144 8429-4 1976 Both dihydropteridine reductase and phenylalanine hydroxylase activities were found to be higher in cells adapted to a medium containing L-phenylalanine or L-tyrosine as the sole carbon source than in those grown in L-asparagine. Phenylalanine 137-152 phenylalanine hydroxylase Homo sapiens 36-61 34057292-1 2021 Phenylketonuria (PKU), a deficiency in the activity of the enzyme phenylalanine hydroxylase, leads to toxic levels of phenylalanine (Phe) in the blood and brain. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 66-91 5686299-0 1968 Phenylalanine hydroxylase activity towards two substrates simultaneously: enhancement of inhibition by phenylalanine, tryptophan and their derivatives. Phenylalanine 103-116 phenylalanine hydroxylase Homo sapiens 0-25 33221376-1 2021 Phenylalanine hydroxylase (PAH) is an allosteric enzyme that maintains phenylalanine (Phe) below neurotoxic levels; its failure results in phenylketonuria, an inborn error of amino acid metabolism. Phenylalanine 71-84 phenylalanine hydroxylase Homo sapiens 0-25 33485250-5 2021 For the model substances maleic acid and phenylalanine, we demonstrate that a custom-made genetic algorithm is able to extract up to nine parameters of a multispecies isotherm from experimental data covering a broad pH-range. Phenylalanine 41-54 phenylalanine hydroxylase Homo sapiens 216-218 33465300-1 2021 BACKGROUND: The impairment of the hepatic enzyme phenylalanine hydroxylase (PAH) causes elevation of phenylalanine levels in blood and other body fluids resulting in the most common inborn error of amino acid metabolism (phenylketonuria). Phenylalanine 49-62 phenylalanine hydroxylase Homo sapiens 76-79 32217972-7 2020 Although phenylalanine levels are increased in the breast milk of patients with PAH deficiency, breastfed infants who do not have PAH deficiency have normal enzyme levels and no dietary restriction. Phenylalanine 9-22 phenylalanine hydroxylase Homo sapiens 80-83 33260674-2 2020 Alterations in the level of PAH leads to the toxic accumulation of phenylalanine in the blood and brain. Phenylalanine 67-80 phenylalanine hydroxylase Homo sapiens 28-31 32668217-9 2020 PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). Phenylalanine 98-111 phenylalanine hydroxylase Homo sapiens 0-3 32742934-1 2020 Background: Accumulation of phenylalanine (Phe) due to deficiency in the enzyme phenylalanine hydroxylase (PAH), responsible for the conversion of Phe into tyrosine leads to Phenylketonuria (PKU), a rare autosomal recessive inborn error of metabolism with a mean prevalence of approximately 1:10,000 to 1:15,000 newborns. Phenylalanine 28-41 phenylalanine hydroxylase Homo sapiens 107-110 32742934-1 2020 Background: Accumulation of phenylalanine (Phe) due to deficiency in the enzyme phenylalanine hydroxylase (PAH), responsible for the conversion of Phe into tyrosine leads to Phenylketonuria (PKU), a rare autosomal recessive inborn error of metabolism with a mean prevalence of approximately 1:10,000 to 1:15,000 newborns. Phenylalanine 43-46 phenylalanine hydroxylase Homo sapiens 107-110 32742934-1 2020 Background: Accumulation of phenylalanine (Phe) due to deficiency in the enzyme phenylalanine hydroxylase (PAH), responsible for the conversion of Phe into tyrosine leads to Phenylketonuria (PKU), a rare autosomal recessive inborn error of metabolism with a mean prevalence of approximately 1:10,000 to 1:15,000 newborns. Phenylalanine 147-150 phenylalanine hydroxylase Homo sapiens 107-110 33101986-1 2020 Introduction: Phenylketonuria (PKU) is an inborn error of metabolism characterized by pathogenic variants of the phenylalanine hydroxylase (PAH) gene with a resulting accumulation of phenylalanine (Phe) to neurotoxic levels. Phenylalanine 113-126 phenylalanine hydroxylase Homo sapiens 140-143 33101986-1 2020 Introduction: Phenylketonuria (PKU) is an inborn error of metabolism characterized by pathogenic variants of the phenylalanine hydroxylase (PAH) gene with a resulting accumulation of phenylalanine (Phe) to neurotoxic levels. Phenylalanine 14-17 phenylalanine hydroxylase Homo sapiens 113-138 33101986-1 2020 Introduction: Phenylketonuria (PKU) is an inborn error of metabolism characterized by pathogenic variants of the phenylalanine hydroxylase (PAH) gene with a resulting accumulation of phenylalanine (Phe) to neurotoxic levels. Phenylalanine 14-17 phenylalanine hydroxylase Homo sapiens 140-143 32883979-1 2020 Phenylalanine hydroxylase (PAH) deficiency leads to phenylalanine accumulation and results in phenylketonuria (PKU). Phenylalanine 52-65 phenylalanine hydroxylase Homo sapiens 0-25 32450880-1 2020 BACKGROUND: Phenylketonuria (PKU) is an inherited metabolic disorder characterized by reduced activity of phenylalanine hydroxylase resulting in elevated blood phenylalanine (Phe) concentration. Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 106-131 31883647-1 2020 BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disease caused by mutations in the PAH gene, resulting in deficiency of phenylalanine hydroxylase (PAH), an enzyme that converts phenylalanine (Phe) to tyrosine (Tyr). Phenylalanine 132-145 phenylalanine hydroxylase Homo sapiens 95-98 31883647-1 2020 BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disease caused by mutations in the PAH gene, resulting in deficiency of phenylalanine hydroxylase (PAH), an enzyme that converts phenylalanine (Phe) to tyrosine (Tyr). Phenylalanine 132-145 phenylalanine hydroxylase Homo sapiens 159-162 31883647-1 2020 BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disease caused by mutations in the PAH gene, resulting in deficiency of phenylalanine hydroxylase (PAH), an enzyme that converts phenylalanine (Phe) to tyrosine (Tyr). Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 95-98 31883647-1 2020 BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disease caused by mutations in the PAH gene, resulting in deficiency of phenylalanine hydroxylase (PAH), an enzyme that converts phenylalanine (Phe) to tyrosine (Tyr). Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 159-162 31076506-5 2019 Allosteric Phe binding favors accumulation of an activated PAH tetramer conformation, which is biophysically distinct in solution. Phenylalanine 11-14 phenylalanine hydroxylase Homo sapiens 59-62 33335942-2 2020 Loss-of-function of PAH leads to accumulation of phenylalanine in the blood/body of an untreated patient, which damages the developing brain, causing severe mental retardation. Phenylalanine 49-62 phenylalanine hydroxylase Homo sapiens 20-23 32106880-1 2020 BACKGROUND: Phenylketonuria (PKU; OMIM#261600) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in high phenylalanine (Phe) in blood and brain. Phenylalanine 103-116 phenylalanine hydroxylase Homo sapiens 130-133 32106880-1 2020 BACKGROUND: Phenylketonuria (PKU; OMIM#261600) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in high phenylalanine (Phe) in blood and brain. Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 103-128 32106880-1 2020 BACKGROUND: Phenylketonuria (PKU; OMIM#261600) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in high phenylalanine (Phe) in blood and brain. Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 130-133 31434173-1 2019 Phenylalanine hydroxylase from Chromobacterium violaceum (CvPAH) is a monomeric enzyme that converts phenylalanine to tyrosine. Phenylalanine 101-114 phenylalanine hydroxylase Homo sapiens 0-25 31076506-6 2019 Protein characterization with enzyme kinetics and intrinsic fluorescence revealed that the C29S variant and hPAH are otherwise equivalent in their response to Phe, further supported by their behavior on various chromatography resins and by analytical ultracentrifugation. Phenylalanine 159-162 phenylalanine hydroxylase Homo sapiens 108-112 30864096-1 2019 Phenylalanine hydroxylase (PAH) deficiency is an inborn error of metabolism that results in elevated phenylalanine levels in blood. Phenylalanine 101-114 phenylalanine hydroxylase Homo sapiens 0-25 31118288-1 2019 Phenylalanine hydroxylase (PAH) is a key enzyme in the catabolism of phenylalanine, and mutations in this enzyme cause phenylketonuria (PKU), a genetic disorder that leads to brain damage and mental retardation if untreated. Phenylalanine 69-82 phenylalanine hydroxylase Homo sapiens 0-25 31118288-1 2019 Phenylalanine hydroxylase (PAH) is a key enzyme in the catabolism of phenylalanine, and mutations in this enzyme cause phenylketonuria (PKU), a genetic disorder that leads to brain damage and mental retardation if untreated. Phenylalanine 69-82 phenylalanine hydroxylase Homo sapiens 27-30 31105574-1 2019 Phenylketonuria (PKU) is an inherited metabolic disease characterized by abnormally high concentrations of the essential amino acid L-phenylalanine (Phe) in blood plasma caused by reduced activity of phenylalanine hydroxylase (PAH). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 200-225 30648773-1 2019 Phenylketonuria (PKU) is a genetic disorder caused by variants in the gene encoding phenylalanine hydroxylase (PAH), resulting in accumulation of phenylalanine to neurotoxic levels. Phenylalanine 84-97 phenylalanine hydroxylase Homo sapiens 111-114 30992364-5 2019 We observed that at low pH (<7.5), these histidines are positively charged and interact with phenylalanine residues in a hydrophobic cleft between adjacent tubulin dimers. Phenylalanine 93-106 phenylalanine hydroxylase Homo sapiens 24-26 31038957-1 2019 Phenylalanine hydroxylase (PAH) is an iron enzyme catalyzing the oxidation of l-Phe to l-Tyr during phenylalanine catabolism. Phenylalanine 78-83 phenylalanine hydroxylase Homo sapiens 0-25 31038957-1 2019 Phenylalanine hydroxylase (PAH) is an iron enzyme catalyzing the oxidation of l-Phe to l-Tyr during phenylalanine catabolism. Phenylalanine 78-83 phenylalanine hydroxylase Homo sapiens 27-30 31038957-1 2019 Phenylalanine hydroxylase (PAH) is an iron enzyme catalyzing the oxidation of l-Phe to l-Tyr during phenylalanine catabolism. Phenylalanine 100-113 phenylalanine hydroxylase Homo sapiens 0-25 31038957-1 2019 Phenylalanine hydroxylase (PAH) is an iron enzyme catalyzing the oxidation of l-Phe to l-Tyr during phenylalanine catabolism. Phenylalanine 100-113 phenylalanine hydroxylase Homo sapiens 27-30 30674554-4 2019 Analytical ultracentrifugation establishes that the isolated regulatory domain of R68S PheH is predominantly monomeric in the absence of phenylalanine and dimerizes in its presence, similar to the regulatory domain of the WT enzyme. Phenylalanine 137-150 phenylalanine hydroxylase Homo sapiens 87-91 30504004-1 2019 Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (phe) metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase that converts phe into tyrosine. Phenylalanine 64-67 phenylalanine hydroxylase Homo sapiens 132-157 30504004-1 2019 Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (phe) metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase that converts phe into tyrosine. Phenylalanine 79-82 phenylalanine hydroxylase Homo sapiens 132-157 28182360-1 2017 BACKGROUND: Deficiency of phenylalanine hydroxylase (PAH) enzyme and elevation of phenylalanine in body fluids cause phenylketonuria (PKU). Phenylalanine 26-39 phenylalanine hydroxylase Homo sapiens 53-56 30578407-1 2018 Phenylalanine hydroxylase catalyzes a critical step in the phenylalanine catabolic pathway, and impairment of the human enzyme is linked to phenylketonuria. Phenylalanine 59-72 phenylalanine hydroxylase Homo sapiens 0-25 30201326-14 2018 However, PAH deficient MSCs cultured in 1200 muM PHE (metric defining classical PKU) show significantly reduced mineralization. Phenylalanine 49-52 phenylalanine hydroxylase Homo sapiens 9-12 29777816-1 2018 The genetic disorder phenylketonuria (PKU) is the inability to metabolize phenylalanine because of a lack of the enzyme phenylalanine hydroxylase. Phenylalanine 74-87 phenylalanine hydroxylase Homo sapiens 120-145 29653686-1 2018 BACKGROUND: Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (PAH) deficiency that results in phenylalanine (Phe) accumulation. Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 47-72 28389235-2 2017 We therefore investigated the DNA methylation pattern of the phenylalanine hydroxylase (PAH) gene promoter at different phe levels, and the possibility of DNA methylation pattern changes being a biomarker of high phe exposure in diet free newborns with HPA. Phenylalanine 61-64 phenylalanine hydroxylase Homo sapiens 88-91 28389235-2 2017 We therefore investigated the DNA methylation pattern of the phenylalanine hydroxylase (PAH) gene promoter at different phe levels, and the possibility of DNA methylation pattern changes being a biomarker of high phe exposure in diet free newborns with HPA. Phenylalanine 120-123 phenylalanine hydroxylase Homo sapiens 88-91 30287685-0 2018 Simulations of the regulatory ACT domain of human phenylalanine hydroxylase (PAH) unveil its mechanism of phenylalanine binding. Phenylalanine 50-63 phenylalanine hydroxylase Homo sapiens 77-80 30287685-1 2018 Phenylalanine hydroxylase (PAH) regulates phenylalanine (Phe) levels in mammals to prevent neurotoxicity resulting from high Phe concentrations as observed in genetic disorders leading to hyperphenylalaninemia and phenylketonuria. Phenylalanine 42-55 phenylalanine hydroxylase Homo sapiens 0-25 30287685-1 2018 Phenylalanine hydroxylase (PAH) regulates phenylalanine (Phe) levels in mammals to prevent neurotoxicity resulting from high Phe concentrations as observed in genetic disorders leading to hyperphenylalaninemia and phenylketonuria. Phenylalanine 42-55 phenylalanine hydroxylase Homo sapiens 27-30 30287685-1 2018 Phenylalanine hydroxylase (PAH) regulates phenylalanine (Phe) levels in mammals to prevent neurotoxicity resulting from high Phe concentrations as observed in genetic disorders leading to hyperphenylalaninemia and phenylketonuria. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 27-30 30287685-1 2018 Phenylalanine hydroxylase (PAH) regulates phenylalanine (Phe) levels in mammals to prevent neurotoxicity resulting from high Phe concentrations as observed in genetic disorders leading to hyperphenylalaninemia and phenylketonuria. Phenylalanine 57-60 phenylalanine hydroxylase Homo sapiens 0-25 30287685-1 2018 Phenylalanine hydroxylase (PAH) regulates phenylalanine (Phe) levels in mammals to prevent neurotoxicity resulting from high Phe concentrations as observed in genetic disorders leading to hyperphenylalaninemia and phenylketonuria. Phenylalanine 57-60 phenylalanine hydroxylase Homo sapiens 27-30 30287685-2 2018 PAH senses elevated Phe concentrations by transient allosteric Phe binding to a protein-protein interface between ACT domains of different subunits in a PAH tetramer. Phenylalanine 20-23 phenylalanine hydroxylase Homo sapiens 0-3 30287685-2 2018 PAH senses elevated Phe concentrations by transient allosteric Phe binding to a protein-protein interface between ACT domains of different subunits in a PAH tetramer. Phenylalanine 20-23 phenylalanine hydroxylase Homo sapiens 153-156 30287685-2 2018 PAH senses elevated Phe concentrations by transient allosteric Phe binding to a protein-protein interface between ACT domains of different subunits in a PAH tetramer. Phenylalanine 63-66 phenylalanine hydroxylase Homo sapiens 0-3 30287685-2 2018 PAH senses elevated Phe concentrations by transient allosteric Phe binding to a protein-protein interface between ACT domains of different subunits in a PAH tetramer. Phenylalanine 63-66 phenylalanine hydroxylase Homo sapiens 153-156 30346142-1 2018 Liver phenylalanine hydroxylase (PheH) is an allosteric enzyme that is activated by phenylalanine. Phenylalanine 6-19 phenylalanine hydroxylase Homo sapiens 33-37 30346142-9 2018 The kinetics of activation of PheH are biphasic over a range of phenylalanine concentrations. Phenylalanine 64-77 phenylalanine hydroxylase Homo sapiens 30-34 29909188-1 2018 Phenylketonuria (PKU) is a prevalent inherited metabolic disorder caused by a phenylalanine hydroxylase (PAH) or tetrahydrobiopterin (BH4) deficiency, which leads to the accumulation of phenylalanine (PHE). Phenylalanine 78-91 phenylalanine hydroxylase Homo sapiens 105-108 29909188-1 2018 Phenylketonuria (PKU) is a prevalent inherited metabolic disorder caused by a phenylalanine hydroxylase (PAH) or tetrahydrobiopterin (BH4) deficiency, which leads to the accumulation of phenylalanine (PHE). Phenylalanine 201-204 phenylalanine hydroxylase Homo sapiens 78-103 29909188-1 2018 Phenylketonuria (PKU) is a prevalent inherited metabolic disorder caused by a phenylalanine hydroxylase (PAH) or tetrahydrobiopterin (BH4) deficiency, which leads to the accumulation of phenylalanine (PHE). Phenylalanine 201-204 phenylalanine hydroxylase Homo sapiens 105-108 29454221-2 2018 The rate-limiting step for phenylalanine metabolism is catalyzed by phenylalanine hydroxylase (PAH) and its cofactor tetrahydrobiopterin. Phenylalanine 27-40 phenylalanine hydroxylase Homo sapiens 68-93 29454221-2 2018 The rate-limiting step for phenylalanine metabolism is catalyzed by phenylalanine hydroxylase (PAH) and its cofactor tetrahydrobiopterin. Phenylalanine 27-40 phenylalanine hydroxylase Homo sapiens 95-98 28768147-1 2017 Phenylketonuria (PKU) is an autosomal recessive disorder caused by a defective phenylalanine hydroxylase (PAH), which catalyzes the hydroxylation of l-phenylalanine (l-Phe) to l-tyrosine (l-Tyr) in presence of the cofactor tetrahydrobiopterin (BH4). Phenylalanine 149-164 phenylalanine hydroxylase Homo sapiens 79-104 28768147-1 2017 Phenylketonuria (PKU) is an autosomal recessive disorder caused by a defective phenylalanine hydroxylase (PAH), which catalyzes the hydroxylation of l-phenylalanine (l-Phe) to l-tyrosine (l-Tyr) in presence of the cofactor tetrahydrobiopterin (BH4). Phenylalanine 149-164 phenylalanine hydroxylase Homo sapiens 106-109 28768147-1 2017 Phenylketonuria (PKU) is an autosomal recessive disorder caused by a defective phenylalanine hydroxylase (PAH), which catalyzes the hydroxylation of l-phenylalanine (l-Phe) to l-tyrosine (l-Tyr) in presence of the cofactor tetrahydrobiopterin (BH4). Phenylalanine 166-171 phenylalanine hydroxylase Homo sapiens 79-104 28768147-1 2017 Phenylketonuria (PKU) is an autosomal recessive disorder caused by a defective phenylalanine hydroxylase (PAH), which catalyzes the hydroxylation of l-phenylalanine (l-Phe) to l-tyrosine (l-Tyr) in presence of the cofactor tetrahydrobiopterin (BH4). Phenylalanine 166-171 phenylalanine hydroxylase Homo sapiens 106-109 28768147-2 2017 Defective PAH causes accumulation of phenylalanine, which has neurotoxic effects and leads to dermatological, behavioral, and neurocognitive problems. Phenylalanine 37-50 phenylalanine hydroxylase Homo sapiens 10-13 28645531-1 2017 Phenylketonuria (PKU) and less severe hyperphenylalaninemia (HPA) constitute the most common inborn error of amino acid metabolism, and is most often caused by defects in phenylalanine hydroxylase (PAH) function resulting in accumulation of Phe to neurotoxic levels. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 171-196 28645531-1 2017 Phenylketonuria (PKU) and less severe hyperphenylalaninemia (HPA) constitute the most common inborn error of amino acid metabolism, and is most often caused by defects in phenylalanine hydroxylase (PAH) function resulting in accumulation of Phe to neurotoxic levels. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 198-201 28645531-5 2017 Here we refine this view to address how PKU-associated missense variants can perturb the equilibrium among alternate native PAH structures (resting-state PAH and activated PAH), thus shifting the tipping point of this equilibrium to a neurotoxic Phe concentration. Phenylalanine 246-249 phenylalanine hydroxylase Homo sapiens 124-127 28645531-5 2017 Here we refine this view to address how PKU-associated missense variants can perturb the equilibrium among alternate native PAH structures (resting-state PAH and activated PAH), thus shifting the tipping point of this equilibrium to a neurotoxic Phe concentration. Phenylalanine 246-249 phenylalanine hydroxylase Homo sapiens 154-157 28645531-5 2017 Here we refine this view to address how PKU-associated missense variants can perturb the equilibrium among alternate native PAH structures (resting-state PAH and activated PAH), thus shifting the tipping point of this equilibrium to a neurotoxic Phe concentration. Phenylalanine 246-249 phenylalanine hydroxylase Homo sapiens 154-157 28593914-3 2017 BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. Phenylalanine 104-107 phenylalanine hydroxylase Homo sapiens 35-60 28680815-1 2017 Mammalian phenylalanine hydroxylase (PAH) is a key enzyme in l-phenylalanine (l-Phe) metabolism and is active as a homotetramer. Phenylalanine 61-76 phenylalanine hydroxylase Homo sapiens 10-35 28680815-1 2017 Mammalian phenylalanine hydroxylase (PAH) is a key enzyme in l-phenylalanine (l-Phe) metabolism and is active as a homotetramer. Phenylalanine 61-76 phenylalanine hydroxylase Homo sapiens 37-40 28680815-1 2017 Mammalian phenylalanine hydroxylase (PAH) is a key enzyme in l-phenylalanine (l-Phe) metabolism and is active as a homotetramer. Phenylalanine 78-83 phenylalanine hydroxylase Homo sapiens 10-35 28680815-1 2017 Mammalian phenylalanine hydroxylase (PAH) is a key enzyme in l-phenylalanine (l-Phe) metabolism and is active as a homotetramer. Phenylalanine 78-83 phenylalanine hydroxylase Homo sapiens 37-40 26962957-1 2016 Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Phenylalanine 91-104 phenylalanine hydroxylase Homo sapiens 118-121 28174686-0 2017 PKU mutation p.G46S prevents the stereospecific binding of l-phenylalanine to the dimer of human phenylalanine hydroxylase regulatory domain. Phenylalanine 59-74 phenylalanine hydroxylase Homo sapiens 97-122 28174686-1 2017 Mammalian phenylalanine hydroxylase (PAH) has a potential allosteric regulatory binding site for l-phenylalanine (l-Phe), in addition to its catalytic site. Phenylalanine 97-112 phenylalanine hydroxylase Homo sapiens 10-35 28174686-1 2017 Mammalian phenylalanine hydroxylase (PAH) has a potential allosteric regulatory binding site for l-phenylalanine (l-Phe), in addition to its catalytic site. Phenylalanine 97-112 phenylalanine hydroxylase Homo sapiens 37-40 28174686-1 2017 Mammalian phenylalanine hydroxylase (PAH) has a potential allosteric regulatory binding site for l-phenylalanine (l-Phe), in addition to its catalytic site. Phenylalanine 114-119 phenylalanine hydroxylase Homo sapiens 10-35 28174686-1 2017 Mammalian phenylalanine hydroxylase (PAH) has a potential allosteric regulatory binding site for l-phenylalanine (l-Phe), in addition to its catalytic site. Phenylalanine 114-119 phenylalanine hydroxylase Homo sapiens 37-40 29291362-1 2017 Phenylketonuria (PKU) is the autosomal recessive deficiency of phenylalanine hydroxylase resulting in the accumulation of phenylalanine (Phe) in blood and in the brain. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 63-88 26962957-1 2016 Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Phenylalanine 159-162 phenylalanine hydroxylase Homo sapiens 91-116 26962957-1 2016 Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Phenylalanine 159-162 phenylalanine hydroxylase Homo sapiens 118-121 27145334-8 2016 Together, these results support a model for allostery in PheH in which phenylalanine stabilizes the dimerization of the regulatory domains and exposes the active site for substrate binding and other structural changes needed for activity. Phenylalanine 71-84 phenylalanine hydroxylase Homo sapiens 57-61 26883219-1 2016 Phenylalanine hydroxylase (PAH) deficiency is an inherited metabolic disorder requiring life-long restriction of dietary protein and phenylalanine-free medical food. Phenylalanine 133-146 phenylalanine hydroxylase Homo sapiens 0-25 27049649-1 2016 The multi-domain enzyme phenylalanine hydroxylase (PAH) catalyzes the hydroxylation of dietary I-phenylalanine (Phe) to I-tyrosine. Phenylalanine 112-115 phenylalanine hydroxylase Homo sapiens 24-49 27049649-1 2016 The multi-domain enzyme phenylalanine hydroxylase (PAH) catalyzes the hydroxylation of dietary I-phenylalanine (Phe) to I-tyrosine. Phenylalanine 112-115 phenylalanine hydroxylase Homo sapiens 51-54 27049649-3 2016 Phe is the substrate for the PAH active site, but also an allosteric ligand that increases enzyme activity. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 29-32 27049649-4 2016 Phe has been proposed to bind, in addition to the catalytic domain, a site at the PAH N-terminal regulatory domain (PAH-RD), to activate the enzyme via an unclear mechanism. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 82-85 27049649-4 2016 Phe has been proposed to bind, in addition to the catalytic domain, a site at the PAH N-terminal regulatory domain (PAH-RD), to activate the enzyme via an unclear mechanism. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 116-119 27049649-5 2016 Here we report the crystal structure of human PAH-RD bound with Phe at 1.8 A resolution, revealing a homodimer of ACT folds with Phe bound at the dimer interface. Phenylalanine 64-67 phenylalanine hydroxylase Homo sapiens 46-49 27049649-5 2016 Here we report the crystal structure of human PAH-RD bound with Phe at 1.8 A resolution, revealing a homodimer of ACT folds with Phe bound at the dimer interface. Phenylalanine 129-132 phenylalanine hydroxylase Homo sapiens 46-49 27049649-6 2016 This work delivers the structural evidence to support previous solution studies that a binding site exists in the RD for Phe, and that Phe binding results in dimerization of PAH-RD. Phenylalanine 121-124 phenylalanine hydroxylase Homo sapiens 174-177 27049649-6 2016 This work delivers the structural evidence to support previous solution studies that a binding site exists in the RD for Phe, and that Phe binding results in dimerization of PAH-RD. Phenylalanine 135-138 phenylalanine hydroxylase Homo sapiens 174-177 27049649-7 2016 Consistent with our structural observation, a disease-associated PAH mutant impaired in Phe binding disrupts the monomer:dimer equilibrium of PAH-RD. Phenylalanine 88-91 phenylalanine hydroxylase Homo sapiens 65-68 27049649-7 2016 Consistent with our structural observation, a disease-associated PAH mutant impaired in Phe binding disrupts the monomer:dimer equilibrium of PAH-RD. Phenylalanine 88-91 phenylalanine hydroxylase Homo sapiens 142-145 27049649-8 2016 Our data therefore support an emerging model of PAH allosteric regulation, whereby Phe binds to PAH-RD and mediates the dimerization of regulatory modules that would bring about conformational changes to activate the enzyme. Phenylalanine 83-86 phenylalanine hydroxylase Homo sapiens 48-51 27049649-8 2016 Our data therefore support an emerging model of PAH allosteric regulation, whereby Phe binds to PAH-RD and mediates the dimerization of regulatory modules that would bring about conformational changes to activate the enzyme. Phenylalanine 83-86 phenylalanine hydroxylase Homo sapiens 96-99 27014574-1 2016 BACKGROUND: Phenylketonuria (PKU) is characterized by phenylalanine (Phe) accumulation to toxic levels due to the low activity of phenylalanine-hydroxylase. Phenylalanine 54-67 phenylalanine hydroxylase Homo sapiens 130-155 27014574-1 2016 BACKGROUND: Phenylketonuria (PKU) is characterized by phenylalanine (Phe) accumulation to toxic levels due to the low activity of phenylalanine-hydroxylase. Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 130-155 24628256-1 2015 The mammalian tetrahydrobiopterin (BH4)-dependent phenylalanine hydroxylases (PAH), involved in important metabolic pathways of phenylalanine, belong to non-heme iron-containing aromatic acid hydroxylases" enzyme (AAH) family. Phenylalanine 50-63 phenylalanine hydroxylase Homo sapiens 78-81 25338975-1 2015 BACKGROUND AND OBJECTIVES: Untreated phenylketonuria (PKU), a hereditary metabolic disorder caused by a genetic mutation in phenylalanine hydroxylase (PAH), is characterized by elevated blood phenylalanine (Phe) and severe neurologic disease. Phenylalanine 207-210 phenylalanine hydroxylase Homo sapiens 124-149 25338975-1 2015 BACKGROUND AND OBJECTIVES: Untreated phenylketonuria (PKU), a hereditary metabolic disorder caused by a genetic mutation in phenylalanine hydroxylase (PAH), is characterized by elevated blood phenylalanine (Phe) and severe neurologic disease. Phenylalanine 207-210 phenylalanine hydroxylase Homo sapiens 151-154 25338975-2 2015 Sapropterin dihydrochloride, a synthetic preparation of naturally occurring PAH cofactor tetrahydrobiopterin (BH4), activates residual PAH in a subset of patients, resulting in decreased blood Phe and increased Phe tolerance. Phenylalanine 211-214 phenylalanine hydroxylase Homo sapiens 135-138 26479306-0 2016 Towards the identification of the allosteric Phe-binding site in phenylalanine hydroxylase. Phenylalanine 45-48 phenylalanine hydroxylase Homo sapiens 65-90 26479306-2 2016 PAH, a tetrameric enzyme, is highly regulated and displays positive cooperativity for its substrate, Phe. Phenylalanine 101-104 phenylalanine hydroxylase Homo sapiens 0-3 26351554-1 2015 OBJECTIVES: Phenylketonuria (PKU) is a genetic inborn error of phenylalanine (Phe) metabolism resulting from insufficiency in the hepatic enzyme, phenylalanine hydroxylase (PAH), which leads to elevated levels of Phe in the blood. Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 146-171 26351554-1 2015 OBJECTIVES: Phenylketonuria (PKU) is a genetic inborn error of phenylalanine (Phe) metabolism resulting from insufficiency in the hepatic enzyme, phenylalanine hydroxylase (PAH), which leads to elevated levels of Phe in the blood. Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 173-176 26351554-1 2015 OBJECTIVES: Phenylketonuria (PKU) is a genetic inborn error of phenylalanine (Phe) metabolism resulting from insufficiency in the hepatic enzyme, phenylalanine hydroxylase (PAH), which leads to elevated levels of Phe in the blood. Phenylalanine 78-81 phenylalanine hydroxylase Homo sapiens 146-171 25943030-1 2015 BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disorder caused by deficiency of hepatic phenylalanine hydroxylase (PAH) leading to increased levels of phenylalanine in the plasma. Phenylalanine 101-114 phenylalanine hydroxylase Homo sapiens 128-131 25943030-3 2015 1-(13)C-phenylalanine, a stable isotope can be used to examine phenylalanine metabolism, as the conversion of phenylalanine to tyrosine occurs in vivo via PAH and subsequently releases the carboxyl labeled (13)C as (13)CO2 in breath. Phenylalanine 8-21 phenylalanine hydroxylase Homo sapiens 155-158 25943030-3 2015 1-(13)C-phenylalanine, a stable isotope can be used to examine phenylalanine metabolism, as the conversion of phenylalanine to tyrosine occurs in vivo via PAH and subsequently releases the carboxyl labeled (13)C as (13)CO2 in breath. Phenylalanine 63-76 phenylalanine hydroxylase Homo sapiens 155-158 26000544-1 2015 Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) metabolism characterized by deficient activity of the hepatic enzyme, phenylalanine hydroxylase. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 150-175 26701937-1 2015 Sapropterin enhances phenylalanine hydroxylase activity, thus lowering blood phenylalanine (Phe) concentration while increasing protein tolerance in sapropterin-responsive patients. Phenylalanine 92-95 phenylalanine hydroxylase Homo sapiens 21-46 25299136-0 2014 Phenylalanine binding is linked to dimerization of the regulatory domain of phenylalanine hydroxylase. Phenylalanine 0-13 phenylalanine hydroxylase Homo sapiens 76-101 25614310-1 2015 Phenylketonuria (PKU) is caused by a deficiency or inactivity of the enzyme phenylalanine hydroxylase that converts phenylalanine (Phe) to tyrosine (Tyr). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 76-101 25453233-1 2014 Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. Phenylalanine 92-105 phenylalanine hydroxylase Homo sapiens 0-25 25453233-1 2014 Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. Phenylalanine 92-105 phenylalanine hydroxylase Homo sapiens 27-31 25453233-1 2014 Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. Phenylalanine 147-160 phenylalanine hydroxylase Homo sapiens 0-25 25453233-1 2014 Phenylalanine hydroxylase (PheH), a liver enzyme that catalyzes the hydroxylation of excess phenylalanine in the diet to tyrosine, is activated by phenylalanine. Phenylalanine 147-160 phenylalanine hydroxylase Homo sapiens 27-31 25453233-9 2014 Both results establish that activation of PheH by phenylalanine does not require binding of the amino acid in the active site. Phenylalanine 50-63 phenylalanine hydroxylase Homo sapiens 42-46 24743000-1 2014 BACKGROUND: Phenylketonuria is an inherited disease caused by impaired activity of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine, leading to accumulation of phenylalanine and subsequent neurocognitive dysfunction. Phenylalanine 135-148 phenylalanine hydroxylase Homo sapiens 83-108 24488205-1 2014 Phenylketonuria (PKU) is a disorder caused by a deficiency in phenylalanine hydroxylase activity, which converts phenylalanine (Phe) to tyrosine, leading to hyperphenylalaninemia (HPA) with accumulation of Phe in tissues of patients. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 62-87 24488205-1 2014 Phenylketonuria (PKU) is a disorder caused by a deficiency in phenylalanine hydroxylase activity, which converts phenylalanine (Phe) to tyrosine, leading to hyperphenylalaninemia (HPA) with accumulation of Phe in tissues of patients. Phenylalanine 128-131 phenylalanine hydroxylase Homo sapiens 62-87 24510568-2 2014 METHODS: For 55 patients whose blood Phe concentration was over 2.0 mg/dL, potential mutations in 13 exons and flanking sequences of the PAH gene were detected by PCR and DNA sequencing. Phenylalanine 37-40 phenylalanine hydroxylase Homo sapiens 137-140 25003100-1 2014 BACKGROUND: Phenylketonuria (PKU) is caused by the inherited defect of the phenylalanine hydroxylase enzyme, which converts phenylalanine (Phe) into tyrosine (Tyr). Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 75-100 24244510-1 2013 Phenylalanine hydroxylase (PAH) catalyzes the conversion of L-Phe to L-Tyr. Phenylalanine 60-65 phenylalanine hydroxylase Homo sapiens 0-25 24465804-2 2014 Inflammation, increasingly implicated in schizophrenia, can impair the function of the enzyme Phenylalanine hydroxylase (PAH; which catalyzes the conversion of phenylalanine to tyrosine) and thus lead to elevated phenylalanine levels and reduced tyrosine levels. Phenylalanine 160-173 phenylalanine hydroxylase Homo sapiens 94-119 24465804-2 2014 Inflammation, increasingly implicated in schizophrenia, can impair the function of the enzyme Phenylalanine hydroxylase (PAH; which catalyzes the conversion of phenylalanine to tyrosine) and thus lead to elevated phenylalanine levels and reduced tyrosine levels. Phenylalanine 160-173 phenylalanine hydroxylase Homo sapiens 121-124 24465804-2 2014 Inflammation, increasingly implicated in schizophrenia, can impair the function of the enzyme Phenylalanine hydroxylase (PAH; which catalyzes the conversion of phenylalanine to tyrosine) and thus lead to elevated phenylalanine levels and reduced tyrosine levels. Phenylalanine 213-226 phenylalanine hydroxylase Homo sapiens 94-119 24465804-2 2014 Inflammation, increasingly implicated in schizophrenia, can impair the function of the enzyme Phenylalanine hydroxylase (PAH; which catalyzes the conversion of phenylalanine to tyrosine) and thus lead to elevated phenylalanine levels and reduced tyrosine levels. Phenylalanine 213-226 phenylalanine hydroxylase Homo sapiens 121-124 23792259-3 2013 METHODS: Phenylalanine hydroxylase (PAH) gene mutations have been analyzed by direct DNA sequencing in 30 HPA patients (Phe levels ranging from 2 to 6mg/dL) from Southern Italy who were identified in a neonatal screening program and a genotype-phenotype correlation was performed. Phenylalanine 9-12 phenylalanine hydroxylase Homo sapiens 36-39 25563006-3 2014 In case where PKU patient is responsive to tetrahydrobiopterin treatment, sapropterin restores the impaired activity of the enzyme phenylalanine hydroxylase, resulting in the stimulation of normal Phe metabolism and thereby enhancing patient tolerance to natural products. Phenylalanine 197-200 phenylalanine hydroxylase Homo sapiens 131-156 24244510-1 2013 Phenylalanine hydroxylase (PAH) catalyzes the conversion of L-Phe to L-Tyr. Phenylalanine 60-65 phenylalanine hydroxylase Homo sapiens 27-30 24244510-4 2013 In particular, PAH displays positive cooperativity for L-Phe, which is proposed to bind the enzyme on an allosteric site in the N-terminal regulatory domain (RD), also classified as an ACT domain. Phenylalanine 55-60 phenylalanine hydroxylase Homo sapiens 15-18 23898865-1 2013 BACKGROUND: Phenylalanine hydroxylase (PAH) is the enzyme that metabolizes phenylalanine, an essential amino acid required for catecholamine synthesis. Phenylalanine 75-88 phenylalanine hydroxylase Homo sapiens 12-37 23860686-1 2013 Phenylalanine hydroxylase (PAH) is a non-heme iron enzyme that catalyzes oxidation of phenylalanine to tyrosine, a reaction that must be kept under tight regulatory control. Phenylalanine 86-99 phenylalanine hydroxylase Homo sapiens 0-25 23860686-1 2013 Phenylalanine hydroxylase (PAH) is a non-heme iron enzyme that catalyzes oxidation of phenylalanine to tyrosine, a reaction that must be kept under tight regulatory control. Phenylalanine 86-99 phenylalanine hydroxylase Homo sapiens 27-30 23860686-4 2013 In an attempt to crystallographically characterize substrate binding by PAH from Chromobacterium violaceum, a single-domain monomeric enzyme, electron density for phenylalanine was observed at a distal site 15.7 A from the active site. Phenylalanine 163-176 phenylalanine hydroxylase Homo sapiens 72-75 23940767-1 2013 Phenylketonuria (PKU), an autosomal recessive disorder of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene, leads to childhood mental retardation by exposing neurons to cytotoxic levels of phenylalanine (Phe). Phenylalanine 107-120 phenylalanine hydroxylase Homo sapiens 134-137 23940767-1 2013 Phenylketonuria (PKU), an autosomal recessive disorder of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene, leads to childhood mental retardation by exposing neurons to cytotoxic levels of phenylalanine (Phe). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 107-132 23940767-1 2013 Phenylketonuria (PKU), an autosomal recessive disorder of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene, leads to childhood mental retardation by exposing neurons to cytotoxic levels of phenylalanine (Phe). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 134-137 23898865-1 2013 BACKGROUND: Phenylalanine hydroxylase (PAH) is the enzyme that metabolizes phenylalanine, an essential amino acid required for catecholamine synthesis. Phenylalanine 75-88 phenylalanine hydroxylase Homo sapiens 39-42 23072726-3 2013 Diminished conversion of phenylalanine (Phen) to tyrosine (Tyr), the primary amino acid precursor of DA, has been associated with inflammation, and may reflect decreased activity of the enzyme phenylalanine-hydroxylase (PAH). Phenylalanine 25-38 phenylalanine hydroxylase Homo sapiens 193-218 23072726-3 2013 Diminished conversion of phenylalanine (Phen) to tyrosine (Tyr), the primary amino acid precursor of DA, has been associated with inflammation, and may reflect decreased activity of the enzyme phenylalanine-hydroxylase (PAH). Phenylalanine 40-44 phenylalanine hydroxylase Homo sapiens 193-218 23375473-2 2013 In these patients hepatic phenylalanine hydroxylase system is compromised due to subnormal tetrahydrobiopterin (BH(4)) levels and hydroxylation of phenylalanine (Phe) to tyrosine (Tyr) is reduced with elevated Phe/Tyr ratio 1-2 h after oral Phe administration (100 mg/kg bw) administration. Phenylalanine 162-165 phenylalanine hydroxylase Homo sapiens 26-51 23457044-1 2013 Mammalian phenylalanine hydroxylase (PAH) catalyzes the rate-limiting step in the phenylalanine catabolism, consuming about 75% of the phenylalanine input from the diet and protein catabolism under physiological conditions. Phenylalanine 10-23 phenylalanine hydroxylase Homo sapiens 37-40 23457044-1 2013 Mammalian phenylalanine hydroxylase (PAH) catalyzes the rate-limiting step in the phenylalanine catabolism, consuming about 75% of the phenylalanine input from the diet and protein catabolism under physiological conditions. Phenylalanine 82-95 phenylalanine hydroxylase Homo sapiens 10-35 23457044-1 2013 Mammalian phenylalanine hydroxylase (PAH) catalyzes the rate-limiting step in the phenylalanine catabolism, consuming about 75% of the phenylalanine input from the diet and protein catabolism under physiological conditions. Phenylalanine 82-95 phenylalanine hydroxylase Homo sapiens 37-40 23457044-6 2013 In this review, we discuss these recent studies, which contribute to define the evolutionary adaptation of the PAH structure and function leading to sophisticated regulation for effective catabolic processing of phenylalanine in mammalian organisms. Phenylalanine 212-225 phenylalanine hydroxylase Homo sapiens 111-114 23559577-1 2013 In about 20%-30% of phenylketonuria (PKU) patients (all phenotypes of PAH deficiency), Phe levels may be controlled through phenylalanine hydroxylase cofactor tetrahydrobiopterin therapy. Phenylalanine 87-90 phenylalanine hydroxylase Homo sapiens 124-149 23375473-2 2013 In these patients hepatic phenylalanine hydroxylase system is compromised due to subnormal tetrahydrobiopterin (BH(4)) levels and hydroxylation of phenylalanine (Phe) to tyrosine (Tyr) is reduced with elevated Phe/Tyr ratio 1-2 h after oral Phe administration (100 mg/kg bw) administration. Phenylalanine 210-213 phenylalanine hydroxylase Homo sapiens 26-51 23375473-2 2013 In these patients hepatic phenylalanine hydroxylase system is compromised due to subnormal tetrahydrobiopterin (BH(4)) levels and hydroxylation of phenylalanine (Phe) to tyrosine (Tyr) is reduced with elevated Phe/Tyr ratio 1-2 h after oral Phe administration (100 mg/kg bw) administration. Phenylalanine 210-213 phenylalanine hydroxylase Homo sapiens 26-51 23327364-1 2013 Phenylalanine hydroxylase (PheH) catalyzes the key step in the catabolism of dietary phenylalanine, its hydroxylation to tyrosine using tetrahydrobiopterin (BH(4)) and O(2). Phenylalanine 85-98 phenylalanine hydroxylase Homo sapiens 0-25 23368961-1 2013 The aromatic amino acid hydroxylases tyrosine hydroxylase (TyrH) and phenylalanine hydroxylase (PheH) have essentially identical active sites; however, PheH is nearly incapable of hydroxylating tyrosine, while TyrH can readily hydroxylate both tyrosine and phenylalanine. Phenylalanine 69-82 phenylalanine hydroxylase Homo sapiens 96-100 23368961-1 2013 The aromatic amino acid hydroxylases tyrosine hydroxylase (TyrH) and phenylalanine hydroxylase (PheH) have essentially identical active sites; however, PheH is nearly incapable of hydroxylating tyrosine, while TyrH can readily hydroxylate both tyrosine and phenylalanine. Phenylalanine 69-82 phenylalanine hydroxylase Homo sapiens 152-156 23327364-1 2013 Phenylalanine hydroxylase (PheH) catalyzes the key step in the catabolism of dietary phenylalanine, its hydroxylation to tyrosine using tetrahydrobiopterin (BH(4)) and O(2). Phenylalanine 85-98 phenylalanine hydroxylase Homo sapiens 27-31 23225039-2 2012 METHODS: Thirteen exons and flanking introns of PAH gene in 102 patients with high blood phenylalanine levels (Phe > 120 umol/L) at initial diagnosis were amplified with polymerase chain reaction and analyzed with single strand conformation polymorphism (SSCP), denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. Phenylalanine 89-102 phenylalanine hydroxylase Homo sapiens 48-51 23430494-1 2013 Phenylketonuria (PKU) is an autosomal recessive inherited metabolic disorder caused by a complete or near-complete deficiency of the liver enzyme phenylalanine hydroxylase (PAH), which converts the amino acid phenylalanine to tyrosine, leading to the increase of blood and tissue concentration of phenylalanine to toxic levels. Phenylalanine 146-159 phenylalanine hydroxylase Homo sapiens 173-176 23225039-2 2012 METHODS: Thirteen exons and flanking introns of PAH gene in 102 patients with high blood phenylalanine levels (Phe > 120 umol/L) at initial diagnosis were amplified with polymerase chain reaction and analyzed with single strand conformation polymorphism (SSCP), denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. Phenylalanine 111-114 phenylalanine hydroxylase Homo sapiens 48-51 22477023-1 2012 Phenylketonuria is a recessive autosomal disorder that is caused by a deficiency in the activity of phenylalanine-4-hydroxylase, which converts phenylalanine to tyrosine, leading to the accumulation of phenylalanine and its metabolites phenyllactic acid, phenylacetic acid, and phenylpyruvic acid in the blood and tissues of patients. Phenylalanine 144-157 phenylalanine hydroxylase Homo sapiens 100-127 22300847-3 2012 METHODS: A robust LC-ESI-MSMS PAH assay for the quantification of phenylalanine and tyrosine was developed. Phenylalanine 66-79 phenylalanine hydroxylase Homo sapiens 30-33 23478721-1 2012 The phenylalanine hydroxylase (PAH) in the liver hydroxylates phenylalanine from the diet. Phenylalanine 4-17 phenylalanine hydroxylase Homo sapiens 31-34 22300847-5 2012 RESULTS: The PAH assay was linear for phenylalanine and tyrosine (r(2)>=0.99), with a detection limit of 105 nmol/L for Phe and 398 nmol/L for Tyr. Phenylalanine 38-51 phenylalanine hydroxylase Homo sapiens 13-16 22300847-5 2012 RESULTS: The PAH assay was linear for phenylalanine and tyrosine (r(2)>=0.99), with a detection limit of 105 nmol/L for Phe and 398 nmol/L for Tyr. Phenylalanine 123-126 phenylalanine hydroxylase Homo sapiens 13-16 22300847-8 2012 Compared to the wild-type enzyme, the highest PAH activity at standard conditions (1 mmol/L L-Phe; 200 mumol/L BH(4)) was found for the mutant p.Y417C (76%), followed by p.E390G (54%), p.R261Q (43%), p.I65T (33%), p.E280A (15%), p.R158Q (5%), and p.R408W (2%). Phenylalanine 92-97 phenylalanine hydroxylase Homo sapiens 46-49 21839840-1 2011 Phenylalanine hydroxylase (PAH) is an important metabolic enzyme of aromatic amino acids, which is responsible for the irreversible oxidation of phenylalanine to tyrosine. Phenylalanine 145-158 phenylalanine hydroxylase Homo sapiens 0-25 22005392-2 2012 Phenylalanine hydroxylase is activated by phenylalanine; this activation is inhibited by the physiological reducing substrate tetrahydrobiopterin. Phenylalanine 42-55 phenylalanine hydroxylase Homo sapiens 0-25 21646032-1 2011 BACKGROUND: Phenylketonuria (PKU) results from impaired breakdown of phenylalanine (Phe) due to deficient phenylalanine hydroxylase (PAH) activity. Phenylalanine 12-15 phenylalanine hydroxylase Homo sapiens 133-136 21553452-1 2010 INTRODUCTION: Phenylketonuria is a genetic disorder of metabolism of amino acid phenylalanine, which results in the absence of phenylalanine hydroxylase, an enzyme that catalyzes the conversion of phenylalanine into tyrosine. Phenylalanine 80-93 phenylalanine hydroxylase Homo sapiens 127-152 21527427-5 2011 Experiments in eukaryotic cells revealed that the availability of the active PAH enzyme depends on the phenylalanine-to-BH(4) ratio. Phenylalanine 103-116 phenylalanine hydroxylase Homo sapiens 77-80 21615132-1 2011 Phenylalanine hydroxylase (PheH) is an iron(II)-dependent enzyme that catalyzes the hydroxylation of aromatic amino acid l-phenylalanine (L-Phe) to l-tyrosine (L-Tyr). Phenylalanine 138-143 phenylalanine hydroxylase Homo sapiens 0-25 21615132-1 2011 Phenylalanine hydroxylase (PheH) is an iron(II)-dependent enzyme that catalyzes the hydroxylation of aromatic amino acid l-phenylalanine (L-Phe) to l-tyrosine (L-Tyr). Phenylalanine 138-143 phenylalanine hydroxylase Homo sapiens 27-31 21659675-3 2011 The mutation causes a variable [corrected] dysfunction in PAH, that metabolizes phenylalanine (Phe) to tyrosine (Tyr) with the cofactor tetrahydrobiopterin (BH4). Phenylalanine 80-93 phenylalanine hydroxylase Homo sapiens 58-61 21659675-3 2011 The mutation causes a variable [corrected] dysfunction in PAH, that metabolizes phenylalanine (Phe) to tyrosine (Tyr) with the cofactor tetrahydrobiopterin (BH4). Phenylalanine 95-98 phenylalanine hydroxylase Homo sapiens 58-61 21216643-1 2011 Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase gene (PAH) with consequent elevation of blood phenylalanine (Phe), reduction in tyrosine (Tyr) and elevation of Phe/Tyr ratio (P/T). Phenylalanine 52-65 phenylalanine hydroxylase Homo sapiens 84-87 21216643-1 2011 Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase gene (PAH) with consequent elevation of blood phenylalanine (Phe), reduction in tyrosine (Tyr) and elevation of Phe/Tyr ratio (P/T). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 52-77 21216643-1 2011 Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase gene (PAH) with consequent elevation of blood phenylalanine (Phe), reduction in tyrosine (Tyr) and elevation of Phe/Tyr ratio (P/T). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 84-87 21216643-1 2011 Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase gene (PAH) with consequent elevation of blood phenylalanine (Phe), reduction in tyrosine (Tyr) and elevation of Phe/Tyr ratio (P/T). Phenylalanine 139-142 phenylalanine hydroxylase Homo sapiens 52-77 21216643-1 2011 Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase gene (PAH) with consequent elevation of blood phenylalanine (Phe), reduction in tyrosine (Tyr) and elevation of Phe/Tyr ratio (P/T). Phenylalanine 139-142 phenylalanine hydroxylase Homo sapiens 84-87 20217238-1 2010 Treatment with tetrahydrobiopterin (BH4), the natural cofactor of phenylalanine hydroxylase (PAH), can reduce blood phenylalanine (Phe) levels in patients with BH4-responsive phenylketonuria (PKU). Phenylalanine 131-134 phenylalanine hydroxylase Homo sapiens 66-91 20480196-1 2010 Phenylalanine hydroxylase (PAH) catalyzes the hydroxylation of L-Phe to L-Tyr. Phenylalanine 63-68 phenylalanine hydroxylase Homo sapiens 0-25 20480196-1 2010 Phenylalanine hydroxylase (PAH) catalyzes the hydroxylation of L-Phe to L-Tyr. Phenylalanine 63-68 phenylalanine hydroxylase Homo sapiens 27-30 20480196-2 2010 Dysfunctional PAH results in phenylketonuria and mammalian PAH is therefore highly regulated and displays positive cooperativity for L-Phe (Hill coefficient (h)=2). Phenylalanine 133-138 phenylalanine hydroxylase Homo sapiens 14-17 20480196-2 2010 Dysfunctional PAH results in phenylketonuria and mammalian PAH is therefore highly regulated and displays positive cooperativity for L-Phe (Hill coefficient (h)=2). Phenylalanine 133-138 phenylalanine hydroxylase Homo sapiens 59-62 20480196-3 2010 L-Phe does not bind to the regulatory ACT domain in full-length tetrameric human PAH and cooperativity is elicited by homotropic binding to the catalytic site (Thorolfsson et al. Phenylalanine 0-5 phenylalanine hydroxylase Homo sapiens 81-84 20480196-5 2010 PAH from Caenorhabditis elegans (cePAH) is devoid of cooperativity for L-Phe (h=0.9), and, as shown in this work, structural analysis reveal an additional L-Phe binding site at the regulatory domain of full-length cePAH. Phenylalanine 71-76 phenylalanine hydroxylase Homo sapiens 0-3 20480196-5 2010 PAH from Caenorhabditis elegans (cePAH) is devoid of cooperativity for L-Phe (h=0.9), and, as shown in this work, structural analysis reveal an additional L-Phe binding site at the regulatory domain of full-length cePAH. Phenylalanine 155-160 phenylalanine hydroxylase Homo sapiens 0-3 20480196-11 2010 Our results support that the acquisition of positive cooperativity in mammalian forms of PAH is accompanied by a closure of the regulatory L: -Phe binding site. Phenylalanine 143-146 phenylalanine hydroxylase Homo sapiens 89-92 19913839-1 2010 Conflicting results have been reported concerning the efficacy of tetrahydrobiopterin (BH4), the cofactor of phenylalanine hydroxylase, for reducing phenylalanine (Phe) concentration in phenylketonuria (PKU). Phenylalanine 164-167 phenylalanine hydroxylase Homo sapiens 109-134 20667834-2 2010 PAH is complexly regulated by its substrate L-Phenylalanine and its natural cofactor 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)). Phenylalanine 44-59 phenylalanine hydroxylase Homo sapiens 0-3 23056707-1 2010 OBJECTIVE: Phenylalanine hydroxylase or its cofactor, tetrahydrobiopterin (BH(4)), deficiency causes accumulation of phenylalanine in body fluids and central nervous system. Phenylalanine 117-130 phenylalanine hydroxylase Homo sapiens 11-36 20714359-2 2010 PKU is caused by an inherited deficiency of the enzyme phenylalanine hydroxylase (PAH), and the pathophysiology of the disorder is related to chronic accumulation of the free amino acid phenylalanine in tissues. Phenylalanine 55-68 phenylalanine hydroxylase Homo sapiens 82-85 20714359-5 2010 Sapropterin dihydrochloride is a synthetic version of tetrahydrobiopterin, the naturally occurring pterin cofactor that is required for PAH-mediated phenylalanine hydroxylation. Phenylalanine 149-162 phenylalanine hydroxylase Homo sapiens 136-139 30780801-2 2010 It is essential for the conversion of phenylalanine (Phe) by phenylalanine-4-hydroxylase (PAH) to tyrosine. Phenylalanine 38-51 phenylalanine hydroxylase Homo sapiens 61-88 30780801-2 2010 It is essential for the conversion of phenylalanine (Phe) by phenylalanine-4-hydroxylase (PAH) to tyrosine. Phenylalanine 53-56 phenylalanine hydroxylase Homo sapiens 61-88 20187763-1 2010 AIM: Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe), and production of the phenylketonuria disease. Phenylalanine 186-199 phenylalanine hydroxylase Homo sapiens 5-30 20187763-1 2010 AIM: Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe), and production of the phenylketonuria disease. Phenylalanine 186-199 phenylalanine hydroxylase Homo sapiens 32-35 20187763-1 2010 AIM: Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe), and production of the phenylketonuria disease. Phenylalanine 186-199 phenylalanine hydroxylase Homo sapiens 78-81 20187763-1 2010 AIM: Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe), and production of the phenylketonuria disease. Phenylalanine 186-199 phenylalanine hydroxylase Homo sapiens 78-81 20187763-1 2010 AIM: Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe), and production of the phenylketonuria disease. Phenylalanine 5-8 phenylalanine hydroxylase Homo sapiens 32-35 20187763-1 2010 AIM: Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe), and production of the phenylketonuria disease. Phenylalanine 5-8 phenylalanine hydroxylase Homo sapiens 78-81 20187763-1 2010 AIM: Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe), and production of the phenylketonuria disease. Phenylalanine 5-8 phenylalanine hydroxylase Homo sapiens 78-81 19194782-10 2009 The different phenylalanine tolerance in pregnancies with PKU-affected and non-affected fetuses suggests that PAH genotype and metabolic situation of the fetus influence maternal metabolic control. Phenylalanine 14-27 phenylalanine hydroxylase Homo sapiens 110-113 19925861-2 2010 They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). Phenylalanine 46-49 phenylalanine hydroxylase Homo sapiens 82-107 19925861-2 2010 They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). Phenylalanine 46-49 phenylalanine hydroxylase Homo sapiens 109-112 19925861-3 2010 PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr). Phenylalanine 109-112 phenylalanine hydroxylase Homo sapiens 67-70 19925861-3 2010 PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr). Phenylalanine 127-130 phenylalanine hydroxylase Homo sapiens 67-70 19925861-12 2010 ART was found to decrease phe/tyr and this change could indicate and influence on PAH activity. Phenylalanine 26-29 phenylalanine hydroxylase Homo sapiens 82-85 20063067-1 2010 Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation due to defects in the enzyme phenylalanine hydroxylase (PAH). Phenylalanine 73-86 phenylalanine hydroxylase Homo sapiens 135-160 20063067-1 2010 Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation due to defects in the enzyme phenylalanine hydroxylase (PAH). Phenylalanine 73-86 phenylalanine hydroxylase Homo sapiens 162-165 20063067-1 2010 Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation due to defects in the enzyme phenylalanine hydroxylase (PAH). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 135-160 20063067-1 2010 Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation due to defects in the enzyme phenylalanine hydroxylase (PAH). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 162-165 20063067-3 2010 Some individuals with PKU respond to tetrahydrobiopterin (BH4) treatment, the natural cofactor of PAH, by a reduction in blood Phe concentrations.We tested 12 patients with PKU, 8-29 years of age, all carrying the common Y414C mutation in the PAH gene. Phenylalanine 127-130 phenylalanine hydroxylase Homo sapiens 98-101 20134300-2 2009 Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) metabolism characterized by a deficiency of the hepatic enzyme, phenylalanine hydroxylase, an enzyme responsible for the conversion of phenylalanine to tyrosine, and elevated levels of Phe and Phe metabolite. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 144-169 19747868-2 2009 Phe tolerance (mg phe/kg body weight/day) is the amount of phe those with PKU can consume and maintain acceptable blood phe levels; it requires individual assessment because of varying phenylalanine hydroxylase activity. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 185-210 20134300-2 2009 Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) metabolism characterized by a deficiency of the hepatic enzyme, phenylalanine hydroxylase, an enzyme responsible for the conversion of phenylalanine to tyrosine, and elevated levels of Phe and Phe metabolite. Phenylalanine 60-73 phenylalanine hydroxylase Homo sapiens 144-169 20134300-2 2009 Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) metabolism characterized by a deficiency of the hepatic enzyme, phenylalanine hydroxylase, an enzyme responsible for the conversion of phenylalanine to tyrosine, and elevated levels of Phe and Phe metabolite. Phenylalanine 75-78 phenylalanine hydroxylase Homo sapiens 144-169 20134300-2 2009 Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) metabolism characterized by a deficiency of the hepatic enzyme, phenylalanine hydroxylase, an enzyme responsible for the conversion of phenylalanine to tyrosine, and elevated levels of Phe and Phe metabolite. Phenylalanine 75-78 phenylalanine hydroxylase Homo sapiens 144-169 19208488-1 2009 Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to deficient conversion of phenylalanine (Phe) to tyrosine and accumulation of toxic levels of Phe. Phenylalanine 52-65 phenylalanine hydroxylase Homo sapiens 79-82 19560382-4 2009 During this period the animals provide an in vivo model which can be used to study the regulatory effects of phenylalanine on PAH, and for related pediatric metabolic disease in humans; from birth to youth. Phenylalanine 109-122 phenylalanine hydroxylase Homo sapiens 126-129 19557660-1 2009 Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (Phe) metabolism resulting from deficiency of phenylalanine hydroxylase (PAH). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 151-154 18937293-1 2009 Recessive mutations in the phenylalanine hydroxylase (PAH) gene predispose to phenylketonuria (PKU) in conjunction with dietary exposure to phenylalanine. Phenylalanine 27-40 phenylalanine hydroxylase Homo sapiens 54-57 19208488-1 2009 Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to deficient conversion of phenylalanine (Phe) to tyrosine and accumulation of toxic levels of Phe. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 52-77 19208488-1 2009 Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to deficient conversion of phenylalanine (Phe) to tyrosine and accumulation of toxic levels of Phe. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 79-82 19208488-1 2009 Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to deficient conversion of phenylalanine (Phe) to tyrosine and accumulation of toxic levels of Phe. Phenylalanine 140-143 phenylalanine hydroxylase Homo sapiens 52-77 19208488-1 2009 Phenylketonuria (PKU) is caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to deficient conversion of phenylalanine (Phe) to tyrosine and accumulation of toxic levels of Phe. Phenylalanine 140-143 phenylalanine hydroxylase Homo sapiens 79-82 19208488-4 2009 The observation of clinically significant reductions in blood Phe levels in a subset of patients with PKU following oral administration of 6R-tetrahydrobiopterin dihydrochloride (BH(4)), a cofactor of PAH, raises the prospect of oral pharmacotherapy for PKU. Phenylalanine 62-65 phenylalanine hydroxylase Homo sapiens 201-204 19276420-1 2009 Experiments were performed to investigate the activity of hepatic Phe hydroxylase (PAH) and plasma amino acid concentrations under conditions of Phe imbalance or toxicity in chicks fed on experimental diets from 7 to 14 or 16 d of age. Phenylalanine 66-69 phenylalanine hydroxylase Homo sapiens 83-86 19276420-4 2009 Correcting the imbalance by adding 1.12% Phe to the diet prevented the growth impairment and increased the activity of PAH. Phenylalanine 41-44 phenylalanine hydroxylase Homo sapiens 119-122 19276420-7 2009 The activity of PAH was not significantly affected by 2% Phe, but it increased in chicks fed the corrected diet. Phenylalanine 57-60 phenylalanine hydroxylase Homo sapiens 16-19 19276420-11 2009 The addition of Phe significantly increased hepatic PAH activity, but there was no detectable main effect of the IAA - Phe and no interaction. Phenylalanine 16-19 phenylalanine hydroxylase Homo sapiens 52-55 19276420-13 2009 We conclude that hepatic PAH activity in chicks variably increases in response to Phe or a 10% dietary supplement of indispensable amino acids including Phe but does not increase in response to IAA - Phe when the amino acids are added to a diet that is marginally adequate in Phe. Phenylalanine 82-85 phenylalanine hydroxylase Homo sapiens 25-28 19276420-13 2009 We conclude that hepatic PAH activity in chicks variably increases in response to Phe or a 10% dietary supplement of indispensable amino acids including Phe but does not increase in response to IAA - Phe when the amino acids are added to a diet that is marginally adequate in Phe. Phenylalanine 153-156 phenylalanine hydroxylase Homo sapiens 25-28 19276420-13 2009 We conclude that hepatic PAH activity in chicks variably increases in response to Phe or a 10% dietary supplement of indispensable amino acids including Phe but does not increase in response to IAA - Phe when the amino acids are added to a diet that is marginally adequate in Phe. Phenylalanine 153-156 phenylalanine hydroxylase Homo sapiens 25-28 19276420-13 2009 We conclude that hepatic PAH activity in chicks variably increases in response to Phe or a 10% dietary supplement of indispensable amino acids including Phe but does not increase in response to IAA - Phe when the amino acids are added to a diet that is marginally adequate in Phe. Phenylalanine 153-156 phenylalanine hydroxylase Homo sapiens 25-28 23045014-2 2009 PAH is a non-heme-iron-dependent protein that normally catalyzes the C-oxidation of phenylalanine (Phe) to tyrosine (Tyr) in the presence of BH(4), utilizing molecular dioxygen as an additional substrate. Phenylalanine 99-102 phenylalanine hydroxylase Homo sapiens 0-3 23045014-2 2009 PAH is a non-heme-iron-dependent protein that normally catalyzes the C-oxidation of phenylalanine (Phe) to tyrosine (Tyr) in the presence of BH(4), utilizing molecular dioxygen as an additional substrate. Phenylalanine 84-97 phenylalanine hydroxylase Homo sapiens 0-3 18701209-4 2008 Oxidative stress resulting from chronic immune activation and inflammation could impair activity of phenylalanine (4)-hydroxylase (PAH) and thus give rise to increased phenylalanine concentrations. Phenylalanine 100-113 phenylalanine hydroxylase Homo sapiens 131-134 19036622-4 2009 These same mutant proteins express between 23% and 76% of the wild type PAH activity when phenylalanine was used as the substrate. Phenylalanine 90-103 phenylalanine hydroxylase Homo sapiens 72-75 19036622-5 2009 The PAH mutant proteins (R158Q, I174T and R408W) that result in the classical phenylketonuria (PKU) phenotype expressing 0.2-1.8% of the wild type PAH activity when using phenylalanine as substrate were found to have <0.1% of the wild type PAH activity when SCMC was used as the substrate. Phenylalanine 171-184 phenylalanine hydroxylase Homo sapiens 4-7 19036622-5 2009 The PAH mutant proteins (R158Q, I174T and R408W) that result in the classical phenylketonuria (PKU) phenotype expressing 0.2-1.8% of the wild type PAH activity when using phenylalanine as substrate were found to have <0.1% of the wild type PAH activity when SCMC was used as the substrate. Phenylalanine 171-184 phenylalanine hydroxylase Homo sapiens 147-150 19036622-5 2009 The PAH mutant proteins (R158Q, I174T and R408W) that result in the classical phenylketonuria (PKU) phenotype expressing 0.2-1.8% of the wild type PAH activity when using phenylalanine as substrate were found to have <0.1% of the wild type PAH activity when SCMC was used as the substrate. Phenylalanine 171-184 phenylalanine hydroxylase Homo sapiens 147-150 19036622-6 2009 Mutations that result in PAH proteins retaining some residual PAH activity with phenylalanine as substrate have <2.0% residual activity when SCMC was used as a substrate. Phenylalanine 80-93 phenylalanine hydroxylase Homo sapiens 25-28 19036622-6 2009 Mutations that result in PAH proteins retaining some residual PAH activity with phenylalanine as substrate have <2.0% residual activity when SCMC was used as a substrate. Phenylalanine 80-93 phenylalanine hydroxylase Homo sapiens 62-65 18701209-8 2008 The phenylalanine to tyrosine ratio (phe/tyr), an estimate of PAH activity, correlated somewhat stronger with sTNF-R75 (rs=0.549; p<0.01) and neopterin (rs=0.497; p=0.01). Phenylalanine 4-17 phenylalanine hydroxylase Homo sapiens 62-65 18701209-8 2008 The phenylalanine to tyrosine ratio (phe/tyr), an estimate of PAH activity, correlated somewhat stronger with sTNF-R75 (rs=0.549; p<0.01) and neopterin (rs=0.497; p=0.01). Phenylalanine 4-7 phenylalanine hydroxylase Homo sapiens 62-65 18701209-11 2008 The relationship between oxidative stress marker isoprostane-8 and phenylalanine as well as sTNF-R75 concentrations suggests a link between reactive oxygen species formed during chronic immune activation and inflammation and the decline of PAH activity, which might underlie the increase of phe/tyr (248 words). Phenylalanine 67-80 phenylalanine hydroxylase Homo sapiens 240-243 18460651-3 2008 CePAH presents similar molecular and kinetic properties to human PAH [S(0.5)(L-Phe) approximately 150 microM; K(m) for tetrahydrobiopterin (BH(4)) approximately 35 microM and comparable V(max)], but cePAH is devoid of positive cooperativity for L-Phe, an important regulatory mechanism of mammalian PAH that protects the nervous system from excess L-Phe. Phenylalanine 77-82 phenylalanine hydroxylase Homo sapiens 2-5 18608740-1 2008 Previous investigations into the binding of substrates/cofactors to the PAH active site have only concentrated on Phe, thienylalanine and BH(4). Phenylalanine 114-117 phenylalanine hydroxylase Homo sapiens 72-75 18163176-5 2008 Increased phenylalanine implies insufficient conversion by phenylalanine (4)-hydroxylase (PAH). Phenylalanine 10-23 phenylalanine hydroxylase Homo sapiens 59-88 18163176-5 2008 Increased phenylalanine implies insufficient conversion by phenylalanine (4)-hydroxylase (PAH). Phenylalanine 10-23 phenylalanine hydroxylase Homo sapiens 90-93 18163176-7 2008 This assumption is further supported by the correlation found between higher neopterin concentrations and higher phenylalanine to tyrosine ratio, which estimates efficacy of PAH. Phenylalanine 113-126 phenylalanine hydroxylase Homo sapiens 174-177 18460651-3 2008 CePAH presents similar molecular and kinetic properties to human PAH [S(0.5)(L-Phe) approximately 150 microM; K(m) for tetrahydrobiopterin (BH(4)) approximately 35 microM and comparable V(max)], but cePAH is devoid of positive cooperativity for L-Phe, an important regulatory mechanism of mammalian PAH that protects the nervous system from excess L-Phe. Phenylalanine 77-82 phenylalanine hydroxylase Homo sapiens 65-68 18566668-1 2008 Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine (Phe) metabolism resulting from deficiency of phenylalanine hydroxylase (PAH). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 151-154 18493213-6 2008 RESULTS: From birth to screening test, the amount of Phe tolerated ranged from 704 to 1620 mg, according to the class of PAH deficiency. Phenylalanine 53-56 phenylalanine hydroxylase Homo sapiens 121-124 18210214-1 2008 BACKGROUND: A significant percentage of patients with hyperphenylalaninaemia (HPA) due to primary deficiency of the phenylalanine hydroxylase enzyme (PAH) respond to a dose of tetrahydrobiopterin (BH(4)) with an increased rate of phenylalanine (Phe) disposal. Phenylalanine 116-129 phenylalanine hydroxylase Homo sapiens 150-153 18210214-1 2008 BACKGROUND: A significant percentage of patients with hyperphenylalaninaemia (HPA) due to primary deficiency of the phenylalanine hydroxylase enzyme (PAH) respond to a dose of tetrahydrobiopterin (BH(4)) with an increased rate of phenylalanine (Phe) disposal. Phenylalanine 245-248 phenylalanine hydroxylase Homo sapiens 150-153 17977740-6 2007 In patients suffering from phenylketonuria the hydroxylation of phenylalanine to tyrosine is defective due to lack of phenylalanine hydroxylase. Phenylalanine 64-77 phenylalanine hydroxylase Homo sapiens 118-143 18212372-0 2008 Phenylalanine requirement, imbalance, and dietary excess in one-week-old chicks: growth and phenylalanine hydroxylase activity. Phenylalanine 0-13 phenylalanine hydroxylase Homo sapiens 92-117 18212372-7 2008 The activities of the major hepatic enzyme of Phe catabolism, Phe hydroxylase (PAH), were significantly higher than that of chicks fed the basal diet when the chicks were fed the diets containing IAA - Phe plus 1.1% Phe (P > or = 0.05) but not when chicks were fed the diet containing IAA - Phe alone. Phenylalanine 46-49 phenylalanine hydroxylase Homo sapiens 79-82 18212372-8 2008 The activity of PAH in chicks given the excess (2%) Phe was nearly 4 times the activity of PAH in chicks given the basal diet. Phenylalanine 52-55 phenylalanine hydroxylase Homo sapiens 16-19 18212372-8 2008 The activity of PAH in chicks given the excess (2%) Phe was nearly 4 times the activity of PAH in chicks given the basal diet. Phenylalanine 52-55 phenylalanine hydroxylase Homo sapiens 91-94 18212372-9 2008 Adding IAA - Phe to the diet containing excess Phe also resulted in higher PAH activity than was observed in chicks fed the basal diet, although the activity was significantly lower than observed for chicks receiving the diet containing excess Phe alone (P > or = 0.05). Phenylalanine 13-16 phenylalanine hydroxylase Homo sapiens 75-78 18212372-9 2008 Adding IAA - Phe to the diet containing excess Phe also resulted in higher PAH activity than was observed in chicks fed the basal diet, although the activity was significantly lower than observed for chicks receiving the diet containing excess Phe alone (P > or = 0.05). Phenylalanine 47-50 phenylalanine hydroxylase Homo sapiens 75-78 18212372-10 2008 It is concluded that hepatic PAH activity in chicks increases primarily in response to its substrate, Phe. Phenylalanine 102-105 phenylalanine hydroxylase Homo sapiens 29-32 19326770-8 2008 An investigation of the mechanism of interaction of SCMC with PAH indicated that the drug was a competitive inhibitor of the aromatic C-oxidation of Phe with a calculated K(i) of 17.23 +/- 4.15 mM. Phenylalanine 149-152 phenylalanine hydroxylase Homo sapiens 62-65 17884650-0 2007 Effects of tetrahydrobiopterin and phenylalanine on in vivo human phenylalanine hydroxylase by phenylalanine breath test. Phenylalanine 35-48 phenylalanine hydroxylase Homo sapiens 66-91 15936235-1 2005 The activity of phenylalanine hydroxylase (PAH) is regulated by the levels of both the substrate (L-Phe) and the natural cofactor (6R)-tetrahydrobiopterin (BH4). Phenylalanine 98-103 phenylalanine hydroxylase Homo sapiens 16-41 17968763-1 2007 Phenylketonuria (PKU) and mild hyperphenylalaninemia (HPA) are genetic disorders characterized by a deficiency in phenylalanine hydroxylase (PAH), resulting in intellectual impairment if not treated with dietary restriction of phenylalanine intake. Phenylalanine 36-49 phenylalanine hydroxylase Homo sapiens 141-144 17443661-5 2007 The PAH enzyme converts phenylalanine to tyrosine in the presence of molecular oxygen and catalytic amounts of tetrahydrobiopterin (BH4), its nonprotein cofactor. Phenylalanine 24-37 phenylalanine hydroxylase Homo sapiens 4-7 17557244-9 2007 The Phe concentration of patients with BH4 responsive PAH deficiency decreased by 49.24% and 65.35% at 8 h and 24 h after oral BH4, 23 in southern group and 13 in northern group among 36 patients. Phenylalanine 4-7 phenylalanine hydroxylase Homo sapiens 54-57 17557244-11 2007 CONCLUSION: Most of mild and moderate HPA patients affected by PAH deficiency show plasma Phe concentration decrease >30% in 24 h after oral BH4 20 mg/kg, few are classic PKU. Phenylalanine 90-93 phenylalanine hydroxylase Homo sapiens 63-66 16402341-4 2006 Cumulatively these findings suggested that TD was related to phenylalanine metabolism and thus that sequence variants in the gene for phenylalanine hydroxylase (PAH), the rate-limiting enzyme in the catabolism of phenylalanine, could be associated with TD susceptibility. Phenylalanine 61-74 phenylalanine hydroxylase Homo sapiens 134-159 16402341-4 2006 Cumulatively these findings suggested that TD was related to phenylalanine metabolism and thus that sequence variants in the gene for phenylalanine hydroxylase (PAH), the rate-limiting enzyme in the catabolism of phenylalanine, could be associated with TD susceptibility. Phenylalanine 61-74 phenylalanine hydroxylase Homo sapiens 161-164 17658743-2 2007 The residues phenylalanine 254 and tyrosine 325 similarly aid in binding BH4 in phenylalanine hydroxylase. Phenylalanine 13-26 phenylalanine hydroxylase Homo sapiens 80-105 17565982-6 2007 PAH is a key enzyme in the metabolic pathway of phenylalanine. Phenylalanine 48-61 phenylalanine hydroxylase Homo sapiens 0-3 16676991-1 2006 Phenylalanine hydroxylase from Chromobacterium violaceum (cPAH), which catalyzes phenylalanine oxidation to tyrosine, is homologous to the catalytic domain of eukaryotic PAHs. Phenylalanine 81-94 phenylalanine hydroxylase Homo sapiens 0-25 16601866-1 2006 A fall in blood phenylalanine (Phe) after tetrahydrobiopterin (BH(4)) administration is a common trait in phenylalanine hydroxylase (PAH, EC 1.14.16.1) deficiency (McKusick 261600). Phenylalanine 16-29 phenylalanine hydroxylase Homo sapiens 106-131 16601866-1 2006 A fall in blood phenylalanine (Phe) after tetrahydrobiopterin (BH(4)) administration is a common trait in phenylalanine hydroxylase (PAH, EC 1.14.16.1) deficiency (McKusick 261600). Phenylalanine 16-29 phenylalanine hydroxylase Homo sapiens 133-136 16601866-1 2006 A fall in blood phenylalanine (Phe) after tetrahydrobiopterin (BH(4)) administration is a common trait in phenylalanine hydroxylase (PAH, EC 1.14.16.1) deficiency (McKusick 261600). Phenylalanine 31-34 phenylalanine hydroxylase Homo sapiens 106-131 16601866-1 2006 A fall in blood phenylalanine (Phe) after tetrahydrobiopterin (BH(4)) administration is a common trait in phenylalanine hydroxylase (PAH, EC 1.14.16.1) deficiency (McKusick 261600). Phenylalanine 31-34 phenylalanine hydroxylase Homo sapiens 133-136 16640195-1 2005 Phenylketonuria (PKU) is a genetic disorder caused by a partial or complete mutation of the enzyme phenylalanine hydroxylase (PHA), fact that produces high levels of phenylalanine in blood resulting in mental retardation if not diagnosed during the neonatal period. Phenylalanine 99-112 phenylalanine hydroxylase Homo sapiens 126-129 16242984-1 2005 Tetrahydrobiopterin (BH4), the natural cofactor of phenylalanine hydroxylase (EC 1.14.16.1), can reduce blood phenylalanine (Phe) in BH4 sensitive patients with hyperphenylalaninemia (McKuisick 261600). Phenylalanine 125-128 phenylalanine hydroxylase Homo sapiens 51-76 15556637-2 2004 BH4-responsive PAH deficiency is a variant of hyperphenylalaninemia or phenylketonuria (PKU) caused by mutations in the human PAH gene that respond to oral BH4 loading by stimulating enzyme activity and therefore lowering serum phenylalanine. Phenylalanine 51-64 phenylalanine hydroxylase Homo sapiens 15-18 15917086-1 2005 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin (BH(4))-dependent enzyme that catalyzes the hydroxylation of l-Phe to l-Tyr. Phenylalanine 118-123 phenylalanine hydroxylase Homo sapiens 0-25 15917086-1 2005 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin (BH(4))-dependent enzyme that catalyzes the hydroxylation of l-Phe to l-Tyr. Phenylalanine 118-123 phenylalanine hydroxylase Homo sapiens 27-30 15878743-1 2005 Phenylketonuria (PKU) is an autossomal recessive disease caused by phenylalanine-4-hydroxylase deficiency, which is a liver-specific enzyme that catalyzes the hydroxylation of l-phenylalanine (Phe) to l-tyrosine (Tyr). Phenylalanine 176-191 phenylalanine hydroxylase Homo sapiens 67-94 15878743-1 2005 Phenylketonuria (PKU) is an autossomal recessive disease caused by phenylalanine-4-hydroxylase deficiency, which is a liver-specific enzyme that catalyzes the hydroxylation of l-phenylalanine (Phe) to l-tyrosine (Tyr). Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 67-94 15557004-1 2004 Phenylketonuria patients harboring a subset of phenylalanine hydroxylase (PAH) mutations have recently shown normalization of blood phenylalanine levels upon oral administration of the PAH cofactor tetrahydrobiopterin [(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4)]. Phenylalanine 47-60 phenylalanine hydroxylase Homo sapiens 74-77 15557004-1 2004 Phenylketonuria patients harboring a subset of phenylalanine hydroxylase (PAH) mutations have recently shown normalization of blood phenylalanine levels upon oral administration of the PAH cofactor tetrahydrobiopterin [(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4)]. Phenylalanine 47-60 phenylalanine hydroxylase Homo sapiens 185-188 16046863-1 2005 Phenylketonuria (PKU) is an inherited disease causing increased levels of phenylalanine in body fluids due to deficiency of hepatic phenylalanine hydroxylase (PAH) or other enzymes involved in the phenylalanine metabolism. Phenylalanine 74-87 phenylalanine hydroxylase Homo sapiens 159-162 16046863-1 2005 Phenylketonuria (PKU) is an inherited disease causing increased levels of phenylalanine in body fluids due to deficiency of hepatic phenylalanine hydroxylase (PAH) or other enzymes involved in the phenylalanine metabolism. Phenylalanine 132-145 phenylalanine hydroxylase Homo sapiens 159-162 16046863-2 2005 With the long-term goal of using gene transfer to the skin to remove phenylalanine, we have previously shown that overexpression of PAH, catalyzing the hydroxylation of phenylalanine, and GTP cyclohydrolase (GTP-CH), involved in the formation of the necessary cofactor BH4,are required. Phenylalanine 69-82 phenylalanine hydroxylase Homo sapiens 132-135 15556637-2 2004 BH4-responsive PAH deficiency is a variant of hyperphenylalaninemia or phenylketonuria (PKU) caused by mutations in the human PAH gene that respond to oral BH4 loading by stimulating enzyme activity and therefore lowering serum phenylalanine. Phenylalanine 51-64 phenylalanine hydroxylase Homo sapiens 126-129 15159646-6 2004 This report demonstrates that when discordant phenotypes occur in a family, without protein loading or phenylalanine tolerance test, complete analysis of the PAH gene may be performed in order to support the diagnosis and assist in accurate genetic counselling and patient management. Phenylalanine 103-116 phenylalanine hydroxylase Homo sapiens 158-161 15493924-1 2004 Phenylalanine hydroxylase (PAH) is the key enzyme in the catabolism of L-Phe. Phenylalanine 71-76 phenylalanine hydroxylase Homo sapiens 0-25 15060071-1 2004 Phenylalanine hydroxylase (PAH) is generally considered to undergo a large and reversible conformational transition upon l-Phe binding, which is closely linked to the substrate-induced catalytic activation of this hysteretic enzyme. Phenylalanine 121-126 phenylalanine hydroxylase Homo sapiens 0-25 15060071-1 2004 Phenylalanine hydroxylase (PAH) is generally considered to undergo a large and reversible conformational transition upon l-Phe binding, which is closely linked to the substrate-induced catalytic activation of this hysteretic enzyme. Phenylalanine 121-126 phenylalanine hydroxylase Homo sapiens 27-30 15060071-4 2004 A strong correlation (r(2) = 0.93-0.96) was observed between the l-Phe-induced global conformational transition and V(max) values for wild-type human PAH and the mutant forms K113P, N223D, N426D, and N32D, in contrast to the substitution T427P, which resulted in a tetrameric form with no kinetic cooperativity. Phenylalanine 65-70 phenylalanine hydroxylase Homo sapiens 150-153 14741785-1 2004 Phenylketonuria (PKU) is a disease in which phenylalanine and phenylalanine-derived metabolites build up to neurotoxic levels due to mutations in the phenylalanine hydroxylase gene (PAH). Phenylalanine 44-57 phenylalanine hydroxylase Homo sapiens 150-175 14741785-1 2004 Phenylketonuria (PKU) is a disease in which phenylalanine and phenylalanine-derived metabolites build up to neurotoxic levels due to mutations in the phenylalanine hydroxylase gene (PAH). Phenylalanine 44-57 phenylalanine hydroxylase Homo sapiens 182-185 14741785-1 2004 Phenylketonuria (PKU) is a disease in which phenylalanine and phenylalanine-derived metabolites build up to neurotoxic levels due to mutations in the phenylalanine hydroxylase gene (PAH). Phenylalanine 62-75 phenylalanine hydroxylase Homo sapiens 150-175 14741785-1 2004 Phenylketonuria (PKU) is a disease in which phenylalanine and phenylalanine-derived metabolites build up to neurotoxic levels due to mutations in the phenylalanine hydroxylase gene (PAH). Phenylalanine 62-75 phenylalanine hydroxylase Homo sapiens 182-185 14654659-6 2003 Maternal IQ increased, and the assigned phenylalanine (Phe) levels decreased with decreasing severity of PAH genotype. Phenylalanine 55-58 phenylalanine hydroxylase Homo sapiens 105-108 12744702-1 2003 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin-dependent enzyme that catalyzes the hydroxylation of L-phenylalanine (L-Phe) to L-tyrosine using dioxygen as an additional substrate. Phenylalanine 110-125 phenylalanine hydroxylase Homo sapiens 0-25 12860366-11 2003 The increase in the ratio between PHE and TYR suggests inhibition of the enzyme phenylalanine hydroxylase. Phenylalanine 34-37 phenylalanine hydroxylase Homo sapiens 80-105 12744702-1 2003 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin-dependent enzyme that catalyzes the hydroxylation of L-phenylalanine (L-Phe) to L-tyrosine using dioxygen as an additional substrate. Phenylalanine 110-125 phenylalanine hydroxylase Homo sapiens 27-30 12744702-1 2003 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin-dependent enzyme that catalyzes the hydroxylation of L-phenylalanine (L-Phe) to L-tyrosine using dioxygen as an additional substrate. Phenylalanine 127-132 phenylalanine hydroxylase Homo sapiens 0-25 12744702-1 2003 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin-dependent enzyme that catalyzes the hydroxylation of L-phenylalanine (L-Phe) to L-tyrosine using dioxygen as an additional substrate. Phenylalanine 127-132 phenylalanine hydroxylase Homo sapiens 27-30 12714182-1 2003 Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene (12q22-q24) resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe) and production of the phenylketonuria (PKU) disease. Phenylalanine 193-206 phenylalanine hydroxylase Homo sapiens 0-25 12714182-1 2003 Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene (12q22-q24) resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe) and production of the phenylketonuria (PKU) disease. Phenylalanine 193-206 phenylalanine hydroxylase Homo sapiens 27-30 12714182-1 2003 Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene (12q22-q24) resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe) and production of the phenylketonuria (PKU) disease. Phenylalanine 193-206 phenylalanine hydroxylase Homo sapiens 73-76 12714182-1 2003 Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene (12q22-q24) resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe) and production of the phenylketonuria (PKU) disease. Phenylalanine 193-206 phenylalanine hydroxylase Homo sapiens 73-76 12714182-1 2003 Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene (12q22-q24) resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe) and production of the phenylketonuria (PKU) disease. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 27-30 12714182-1 2003 Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene (12q22-q24) resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe) and production of the phenylketonuria (PKU) disease. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 73-76 12733906-1 2003 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin-dependent, nonheme iron enzyme that catalyzes the hydroxylation of L-Phe to L-Tyr in the rate-limiting step of phenylalanine catabolism. Phenylalanine 124-129 phenylalanine hydroxylase Homo sapiens 0-25 12733906-1 2003 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin-dependent, nonheme iron enzyme that catalyzes the hydroxylation of L-Phe to L-Tyr in the rate-limiting step of phenylalanine catabolism. Phenylalanine 124-129 phenylalanine hydroxylase Homo sapiens 27-30 12714182-1 2003 Phenylalanine hydroxylase (PAH) deficiency is caused by mutations in the PAH gene (12q22-q24) resulting in a primary deficiency of the PAH enzyme activity, intolerance to the dietary intake of phenylalanine (Phe) and production of the phenylketonuria (PKU) disease. Phenylalanine 0-3 phenylalanine hydroxylase Homo sapiens 73-76 12714182-6 2003 In the next step, the presence of 18 common mutations of the PAH gene in 26 of the patients with classical PKU (serum Phe above 20mg/dl) was investigated, using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Phenylalanine 118-121 phenylalanine hydroxylase Homo sapiens 61-64 12655545-8 2003 The intracellular steady-state levels of the mutant PAH enzyme are therefore reduced, leading to an overall decrease in phenylalanine hydroxylation within cells and thus to hyperphenylalaninemia. Phenylalanine 120-133 phenylalanine hydroxylase Homo sapiens 52-55 12696880-1 2003 Phenylalanine hydroxylase, a mononuclear non-heme iron enzyme, catalyzes the hydroxylation of phenylalanine to tyrosine in the presence of oxygen and reduced pterin cofactor. Phenylalanine 94-107 phenylalanine hydroxylase Homo sapiens 0-25 12653545-11 2003 The same conformational changes appear to be involved in the activation of PAH induced by L-Phe. Phenylalanine 90-95 phenylalanine hydroxylase Homo sapiens 75-78 12379147-1 2003 The optical biosensor technique, based on the surface plasmon resonance (SPR) phenomenon, was used for real-time measurements of the slow conformational transition (isomerization) which occurs in human phenylalanine hydroxylase (hPAH) on the binding/dissociation of L-phenylalanine (L-Phe). Phenylalanine 266-281 phenylalanine hydroxylase Homo sapiens 202-227 12644360-1 2003 BACKGROUND: Reports relating phenylalanine kinetics and metabolism to psychiatric disorders led us to undertake the comprehensive screening of the phenylalanine hydroxylase (PAH) coding region and functional testing of discovered mutations in a sample of psychiatric patients and healthy control subjects. Phenylalanine 29-42 phenylalanine hydroxylase Homo sapiens 174-177 12603331-1 2003 The catalytic activity of phenylalanine hydroxylase (PAH, phenylalanine 4-monooxygenase EC 1.14.16.1) is regulated by three main mechanisms, i.e. substrate (l-phenylalanine, L-Phe) activation, pterin cofactor inhibition and phosphorylation of a single serine (Ser16) residue. Phenylalanine 157-172 phenylalanine hydroxylase Homo sapiens 26-51 12603331-1 2003 The catalytic activity of phenylalanine hydroxylase (PAH, phenylalanine 4-monooxygenase EC 1.14.16.1) is regulated by three main mechanisms, i.e. substrate (l-phenylalanine, L-Phe) activation, pterin cofactor inhibition and phosphorylation of a single serine (Ser16) residue. Phenylalanine 174-179 phenylalanine hydroxylase Homo sapiens 26-51 12379147-1 2003 The optical biosensor technique, based on the surface plasmon resonance (SPR) phenomenon, was used for real-time measurements of the slow conformational transition (isomerization) which occurs in human phenylalanine hydroxylase (hPAH) on the binding/dissociation of L-phenylalanine (L-Phe). Phenylalanine 266-281 phenylalanine hydroxylase Homo sapiens 229-233 12379147-1 2003 The optical biosensor technique, based on the surface plasmon resonance (SPR) phenomenon, was used for real-time measurements of the slow conformational transition (isomerization) which occurs in human phenylalanine hydroxylase (hPAH) on the binding/dissociation of L-phenylalanine (L-Phe). Phenylalanine 283-288 phenylalanine hydroxylase Homo sapiens 202-227 12379147-1 2003 The optical biosensor technique, based on the surface plasmon resonance (SPR) phenomenon, was used for real-time measurements of the slow conformational transition (isomerization) which occurs in human phenylalanine hydroxylase (hPAH) on the binding/dissociation of L-phenylalanine (L-Phe). Phenylalanine 283-288 phenylalanine hydroxylase Homo sapiens 229-233 12379147-7 2003 The binding isotherm for tetrameric and dimeric wt-hPAH revealed a [S](0.5)-value of 98+/-7 microM (h =1.0) and 158+/-11 microM, respectively, i.e. for the tetramer it is slightly lower than the value (145+/-5 microM) obtained for the co-operative binding (h =1.6+/-0.4) of L-Phe as measured by the change in intrinsic tryptophan fluorescence. Phenylalanine 274-279 phenylalanine hydroxylase Homo sapiens 51-55 12379147-11 2003 The substrate analogue 3-(2-thienyl)-L-alanine revealed an SPR response comparable with that of L-Phe on binding to wild-type hPAH. Phenylalanine 96-101 phenylalanine hydroxylase Homo sapiens 126-130 12542580-2 2003 Subjects from the same family who share the same mutations in the phenylalanine hydroxylase (PAH) gene are expected to display similar disease courses, and therefore, when blood phenylalanine (Phe) levels, genotype and dietary treatment are all similar, differences in patient outcomes require additional explanations. Phenylalanine 66-79 phenylalanine hydroxylase Homo sapiens 93-96 12542580-2 2003 Subjects from the same family who share the same mutations in the phenylalanine hydroxylase (PAH) gene are expected to display similar disease courses, and therefore, when blood phenylalanine (Phe) levels, genotype and dietary treatment are all similar, differences in patient outcomes require additional explanations. Phenylalanine 193-196 phenylalanine hydroxylase Homo sapiens 66-91 12142458-1 2002 Phenylalanine hydroxylase (PAH) is activated by its substrate phenylalanine, and through phosphorylation by cAMP-dependent protein kinase at Ser16 in the N-terminal autoregulatory sequence of the enzyme. Phenylalanine 62-75 phenylalanine hydroxylase Homo sapiens 0-25 12185072-2 2002 Phosphorylation of phenylalanine hydroxylase (PAH) at Ser(16) by cyclic AMP-dependent protein kinase is a post-translational modification that increases its basal activity and facilitates its activation by the substrate l-Phe. Phenylalanine 220-225 phenylalanine hydroxylase Homo sapiens 19-44 12185072-2 2002 Phosphorylation of phenylalanine hydroxylase (PAH) at Ser(16) by cyclic AMP-dependent protein kinase is a post-translational modification that increases its basal activity and facilitates its activation by the substrate l-Phe. Phenylalanine 220-225 phenylalanine hydroxylase Homo sapiens 46-49 12210276-1 2002 Phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine, shares physical, structural and catalytic properties with tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) that catalyze the rate-limiting steps in the biosynthesis of the neurotransmitters dopamine, noradrenaline, and serotonin. Phenylalanine 67-80 phenylalanine hydroxylase Homo sapiens 0-25 12210276-1 2002 Phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine, shares physical, structural and catalytic properties with tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) that catalyze the rate-limiting steps in the biosynthesis of the neurotransmitters dopamine, noradrenaline, and serotonin. Phenylalanine 67-80 phenylalanine hydroxylase Homo sapiens 27-30 12142458-1 2002 Phenylalanine hydroxylase (PAH) is activated by its substrate phenylalanine, and through phosphorylation by cAMP-dependent protein kinase at Ser16 in the N-terminal autoregulatory sequence of the enzyme. Phenylalanine 62-75 phenylalanine hydroxylase Homo sapiens 27-30 12142458-8 2002 Our results support the model whereby upon phenylalanine binding, the mobile N-terminal 18 residues of PAH associate with the folded core of the molecule; phosphorylation may facilitate this interaction. Phenylalanine 43-56 phenylalanine hydroxylase Homo sapiens 103-106 11723206-2 2001 An extensive evaluation for the usual causes of these difficulties was unrevealing, but her serum phenylalanine concentration was markedly elevated and genetic analysis demonstrated mutations in the phenylalanine hydroxylase gene consistent with classic phenylketonuria. Phenylalanine 98-111 phenylalanine hydroxylase Homo sapiens 199-224 12126628-1 2002 Phenylalanine hydroxylase catalyzes the stereospecific hydroxylation of L-phenylalanine, the committed step in the degradation of this amino acid. Phenylalanine 72-87 phenylalanine hydroxylase Homo sapiens 0-25 12096915-4 2002 The enzyme phenylalanine hydroxylase (PheOH) catalyzes the hydroxylation of l-phenylalanine into l-tyrosine utilizing the cofactors (6R)-l-erythro-5,6,7,8 tetrahydrobiopterin (BH(4)) and molecular oxygen. Phenylalanine 76-91 phenylalanine hydroxylase Homo sapiens 11-36 12056888-0 2002 L-phenylalanine binding and domain organization in human phenylalanine hydroxylase: a differential scanning calorimetry study. Phenylalanine 0-15 phenylalanine hydroxylase Homo sapiens 57-82 12056888-1 2002 Human phenylalanine hydroxylase (hPAH) is a tetrameric enzyme that catalyzes the hydroxylation of L-phenylalanine (L-Phe) to L-tyrosine; a dysfunction of this enzyme causes phenylketonuria. Phenylalanine 98-113 phenylalanine hydroxylase Homo sapiens 6-31 12056888-1 2002 Human phenylalanine hydroxylase (hPAH) is a tetrameric enzyme that catalyzes the hydroxylation of L-phenylalanine (L-Phe) to L-tyrosine; a dysfunction of this enzyme causes phenylketonuria. Phenylalanine 98-113 phenylalanine hydroxylase Homo sapiens 33-37 12056888-1 2002 Human phenylalanine hydroxylase (hPAH) is a tetrameric enzyme that catalyzes the hydroxylation of L-phenylalanine (L-Phe) to L-tyrosine; a dysfunction of this enzyme causes phenylketonuria. Phenylalanine 115-120 phenylalanine hydroxylase Homo sapiens 6-31 12056888-1 2002 Human phenylalanine hydroxylase (hPAH) is a tetrameric enzyme that catalyzes the hydroxylation of L-phenylalanine (L-Phe) to L-tyrosine; a dysfunction of this enzyme causes phenylketonuria. Phenylalanine 115-120 phenylalanine hydroxylase Homo sapiens 33-37 12056888-8 2002 Application of this approach to the L-Phe effect on the DSC thermograms for hPAH suggests that (i) there are no binding sites for L-Phe in the regulatory domains; therefore, contrary to the common belief, the activation of PAH by L-Phe seems to be the result of its homotropic cooperative binding to the active sites. Phenylalanine 36-41 phenylalanine hydroxylase Homo sapiens 76-80 12056888-8 2002 Application of this approach to the L-Phe effect on the DSC thermograms for hPAH suggests that (i) there are no binding sites for L-Phe in the regulatory domains; therefore, contrary to the common belief, the activation of PAH by L-Phe seems to be the result of its homotropic cooperative binding to the active sites. Phenylalanine 36-41 phenylalanine hydroxylase Homo sapiens 77-80 12200907-1 2002 UNLABELLED: The aim of this study was to determine whether any relationship exists between the severity of mutation of the phenylalanine hydroxylase (PAH) gene and the plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr) under fasting and semifasting conditions among heterozygotes in a matched case-control study. Phenylalanine 123-136 phenylalanine hydroxylase Homo sapiens 150-153 12200907-1 2002 UNLABELLED: The aim of this study was to determine whether any relationship exists between the severity of mutation of the phenylalanine hydroxylase (PAH) gene and the plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr) under fasting and semifasting conditions among heterozygotes in a matched case-control study. Phenylalanine 208-211 phenylalanine hydroxylase Homo sapiens 123-148 12200907-1 2002 UNLABELLED: The aim of this study was to determine whether any relationship exists between the severity of mutation of the phenylalanine hydroxylase (PAH) gene and the plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr) under fasting and semifasting conditions among heterozygotes in a matched case-control study. Phenylalanine 208-211 phenylalanine hydroxylase Homo sapiens 150-153 11747434-6 2001 The resulting ternary TPH-BH2-L-Trp structure is very similar to that previously determined by the same methods for the complex of phenylalanine hydroxylase (PAH) with BH2 and L-Phe [Teigen, K., et al. Phenylalanine 176-181 phenylalanine hydroxylase Homo sapiens 131-156 11747434-6 2001 The resulting ternary TPH-BH2-L-Trp structure is very similar to that previously determined by the same methods for the complex of phenylalanine hydroxylase (PAH) with BH2 and L-Phe [Teigen, K., et al. Phenylalanine 176-181 phenylalanine hydroxylase Homo sapiens 158-161 11859869-1 2002 Hyperphenylalaninemia result from a block in the conversion of phenylalanine into tyrosine due to a defect in either the enzyme phenylalanine hydroxylase (98% of subjects) or in the metabolism of the cofactor tetrahydrobiopterin. Phenylalanine 5-18 phenylalanine hydroxylase Homo sapiens 128-153 11326337-4 2001 Database searches were used to identify regions in the N-terminal domain of PAH with homology to the regulatory domain of prephenate dehydratase (PDH), the rate-limiting enzyme in the bacterial phenylalanine biosynthesis pathway. Phenylalanine 194-207 phenylalanine hydroxylase Homo sapiens 76-79 11301319-1 2001 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin (BH(4)) and non-heme iron-dependent enzyme that hydroxylates L-Phe to L-Tyr. Phenylalanine 118-123 phenylalanine hydroxylase Homo sapiens 0-25 11301319-1 2001 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin (BH(4)) and non-heme iron-dependent enzyme that hydroxylates L-Phe to L-Tyr. Phenylalanine 118-123 phenylalanine hydroxylase Homo sapiens 27-30 11326337-6 2001 To examine whether N-terminal PAH mutations affect the ability of PAH to bind phenylalanine at the regulatory domain, wild-type and five mutant (G46S, A47V, T63P/H64N, I65T, and R68S) forms of the N-terminal domain (residues 2-120) of human PAH were expressed as fusion proteins in Escherichia coli. Phenylalanine 78-91 phenylalanine hydroxylase Homo sapiens 66-69 11326337-6 2001 To examine whether N-terminal PAH mutations affect the ability of PAH to bind phenylalanine at the regulatory domain, wild-type and five mutant (G46S, A47V, T63P/H64N, I65T, and R68S) forms of the N-terminal domain (residues 2-120) of human PAH were expressed as fusion proteins in Escherichia coli. Phenylalanine 78-91 phenylalanine hydroxylase Homo sapiens 66-69 11326337-8 2001 Our data suggest that impairment of phenylalanine-mediated activation of PAH may be an important disease-causing mechanism of some N-terminal PAH mutations, which may explain some well-documented genotype-phenotype discrepancies in PAH deficiency. Phenylalanine 36-49 phenylalanine hydroxylase Homo sapiens 73-76 11326337-8 2001 Our data suggest that impairment of phenylalanine-mediated activation of PAH may be an important disease-causing mechanism of some N-terminal PAH mutations, which may explain some well-documented genotype-phenotype discrepancies in PAH deficiency. Phenylalanine 36-49 phenylalanine hydroxylase Homo sapiens 142-145 11382545-0 2001 Dietary supplements of mixtures of indispensable amino acids lacking threonine, phenylalanine or histidine increase the activity of hepatic threonine dehydrogenase, phenylalanine hydroxylase or histidase, respectively, and prevent growth depressions in chicks caused by dietary excesses of threonine, phenylalanine, or histidine* Experiments were carried out to determine whether the addition of a mixture of indispensable amino acids (IAA) lacking in threonine, phenylalanine or histidine, respectively, to a nutritionally complete diet would increase the hepatic activities of the rate-limiting enzymes for catabolism of threonine, phenylalanine or histidine and prevent the adverse effects of the amino acid on growth when the dietary level of the amino acid is excessive. Phenylalanine 80-93 phenylalanine hydroxylase Homo sapiens 165-190 11328945-8 2001 Phenylalanine hydroxylase mutations in the mothers and offspring did not have an independent relationship to congenital heart disease but were related through the basal maternal phenylalanine levels. Phenylalanine 178-191 phenylalanine hydroxylase Homo sapiens 0-25 10964764-9 2000 Simultaneous application of ochratoxin A with phenylalanine could reduce inhibition of phenylalanine hydroxylase, in particular in liver. Phenylalanine 46-59 phenylalanine hydroxylase Homo sapiens 87-112 11405341-5 2001 Recently, there have been several reports of PKU patients showing a normalization of their L-Phe concentrations upon oral administration of the natural cofactor to PAH, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4). Phenylalanine 91-96 phenylalanine hydroxylase Homo sapiens 164-167 11405341-9 2001 Oral administration of excess BH4 thus makes it possible for these mutant enzymes to suppress their low binding affinity for BH4, enabling this subset of PAH mutations to perform the L-Phe hydroxylation reaction. Phenylalanine 183-188 phenylalanine hydroxylase Homo sapiens 154-157 10980574-1 2000 Phenylalanine hydroxylase (PAH) is the enzyme that converts phenylalanine to tyrosine as a rate-limiting step in phenylalanine catabolism and protein and neurotransmitter biosynthesis. Phenylalanine 60-73 phenylalanine hydroxylase Homo sapiens 0-25 10980574-1 2000 Phenylalanine hydroxylase (PAH) is the enzyme that converts phenylalanine to tyrosine as a rate-limiting step in phenylalanine catabolism and protein and neurotransmitter biosynthesis. Phenylalanine 113-126 phenylalanine hydroxylase Homo sapiens 0-25 11161839-1 2001 Phenylalanine hydroxylase (PAH) is a homotetrameric enzyme that catalyzes the conversion of phenylalanine to tyrosine, the rate-limiting step of phenylalanine disposal in humans. Phenylalanine 92-105 phenylalanine hydroxylase Homo sapiens 0-25 11161839-1 2001 Phenylalanine hydroxylase (PAH) is a homotetrameric enzyme that catalyzes the conversion of phenylalanine to tyrosine, the rate-limiting step of phenylalanine disposal in humans. Phenylalanine 92-105 phenylalanine hydroxylase Homo sapiens 27-30 11161839-1 2001 Phenylalanine hydroxylase (PAH) is a homotetrameric enzyme that catalyzes the conversion of phenylalanine to tyrosine, the rate-limiting step of phenylalanine disposal in humans. Phenylalanine 145-158 phenylalanine hydroxylase Homo sapiens 0-25 11161839-1 2001 Phenylalanine hydroxylase (PAH) is a homotetrameric enzyme that catalyzes the conversion of phenylalanine to tyrosine, the rate-limiting step of phenylalanine disposal in humans. Phenylalanine 145-158 phenylalanine hydroxylase Homo sapiens 27-30 11161839-2 2001 Primary dysfunction of PAH caused by mutations in the PAH gene results in hyperphenylalaninemia, which may impair cognitive development unless corrected by dietary restriction of phenylalanine. Phenylalanine 79-92 phenylalanine hydroxylase Homo sapiens 23-26 11161839-2 2001 Primary dysfunction of PAH caused by mutations in the PAH gene results in hyperphenylalaninemia, which may impair cognitive development unless corrected by dietary restriction of phenylalanine. Phenylalanine 79-92 phenylalanine hydroxylase Homo sapiens 54-57 11163771-1 2001 Phenylalanine hydroxylase (PAH) is activated by its substrate phenylalanine and inhibited by its cofactor tetrahydrobiopterin (BH(4)). Phenylalanine 62-75 phenylalanine hydroxylase Homo sapiens 0-25 11163771-1 2001 Phenylalanine hydroxylase (PAH) is activated by its substrate phenylalanine and inhibited by its cofactor tetrahydrobiopterin (BH(4)). Phenylalanine 62-75 phenylalanine hydroxylase Homo sapiens 27-30 11163771-4 2001 Our data support the model where the N-terminal sequence of PAH acts as an intrasteric autoregulatory sequence, responsible for transmitting the effect of phenylalanine activation to the active site. Phenylalanine 155-168 phenylalanine hydroxylase Homo sapiens 60-63 11175307-0 2000 Development of a skin-based metabolic sink for phenylalanine by overexpression of phenylalanine hydroxylase and GTP cyclohydrolase in primary human keratinocytes. Phenylalanine 47-60 phenylalanine hydroxylase Homo sapiens 82-107 10610798-0 1999 The structural basis of the recognition of phenylalanine and pterin cofactors by phenylalanine hydroxylase: implications for the catalytic mechanism. Phenylalanine 43-56 phenylalanine hydroxylase Homo sapiens 81-106 10767173-8 2000 The Pah enzyme activities of the various models correlate inversely with the corresponding phenylalanine levels in plasma and brain and the delay in plasma clearance response following a phenylalanine challenge. Phenylalanine 91-104 phenylalanine hydroxylase Homo sapiens 4-7 10767173-8 2000 The Pah enzyme activities of the various models correlate inversely with the corresponding phenylalanine levels in plasma and brain and the delay in plasma clearance response following a phenylalanine challenge. Phenylalanine 187-200 phenylalanine hydroxylase Homo sapiens 4-7 10767175-7 2000 The enzyme kinetic studies of the V388M mutant protein revealed that this enzyme was a kinetic variant form of hPAH with a reduced affinity for l-phenylalanine and for the natural cofactor ((6R)-tetrahydrobiopterin). Phenylalanine 144-159 phenylalanine hydroxylase Homo sapiens 111-115 10610798-1 1999 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin and non-heme iron-dependent enzyme that hydroxylates L-Phe to l-Tyr using molecular oxygen as additional substrate. Phenylalanine 110-115 phenylalanine hydroxylase Homo sapiens 0-25 10610798-1 1999 Phenylalanine hydroxylase (PAH) is a tetrahydrobiopterin and non-heme iron-dependent enzyme that hydroxylates L-Phe to l-Tyr using molecular oxygen as additional substrate. Phenylalanine 110-115 phenylalanine hydroxylase Homo sapiens 27-30 10610798-3 1999 The conformation and distances to the catalytic iron of both L-Phe and the cofactor analogue L-erythro-7,8-dihydrobiopterin (BH2) simultaneously bound to recombinant human PAH have been estimated by (1)H NMR. Phenylalanine 61-66 phenylalanine hydroxylase Homo sapiens 172-175 10462491-2 1999 In addition, a significantly more efficient autocrine turnover of L-phenylalanine to L-tyrosine via intracellular phenylalanine hydroxylase was demonstrated in melanocytes. Phenylalanine 66-81 phenylalanine hydroxylase Homo sapiens 114-139 10643998-1 1999 It has been recognised that the active transport of L-phenylalanine and its autocrine turnover to L-tyrosine via phenylalanine hydroxylase in the cytosol of epidermal melanocytes provides the majority of the L-tyrosine pool for melanogenesis. Phenylalanine 52-67 phenylalanine hydroxylase Homo sapiens 113-138 10462491-5 1999 The transport of extracellular L-phenylalanine and its intracellular metabolism to L-tyrosine via intracellular phenylalanine hydroxylase are coupled to calcium uptake/efflux, whereas L-tyrosine uptake is calcium independent. Phenylalanine 31-46 phenylalanine hydroxylase Homo sapiens 112-137 9642259-1 1998 Phenylalanine hydroxylase (PheOH) catalyzes the conversion of L-phenylalanine to L-tyrosine, the rate-limiting step in the oxidative degradation of phenylalanine. Phenylalanine 62-77 phenylalanine hydroxylase Homo sapiens 0-25 10444341-1 1999 Phenylalanine hydroxylase (PAH) is the key enzyme in phenylalanine metabolism. Phenylalanine 53-66 phenylalanine hydroxylase Homo sapiens 0-25 10444341-1 1999 Phenylalanine hydroxylase (PAH) is the key enzyme in phenylalanine metabolism. Phenylalanine 53-66 phenylalanine hydroxylase Homo sapiens 27-30 10444341-9 1999 Human kidney PAH may play a significant role in phenylalanine homeostasis of the organism, as impaired phenylalanine hydroxylation has been observed in renal failure and differences in the regulation of the kidney versus the liver enzyme have been indicated. Phenylalanine 48-61 phenylalanine hydroxylase Homo sapiens 13-16 10356314-9 1999 The result of treatment with the phenylalanine-restricted diet was that these individuals could participate in society and were able to arrest the neurodegenerative course characteristic of persons with mutations classified as severe in the phenylalanine hydroxylase gene. Phenylalanine 33-46 phenylalanine hydroxylase Homo sapiens 241-266 10356315-2 1999 For this reason, various indexes that measure plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr), as an expression of Phe metabolizing capacity, have been used for the detection of carriers for mutations in the PAH gene. Phenylalanine 71-84 phenylalanine hydroxylase Homo sapiens 224-227 10356315-2 1999 For this reason, various indexes that measure plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr), as an expression of Phe metabolizing capacity, have been used for the detection of carriers for mutations in the PAH gene. Phenylalanine 86-89 phenylalanine hydroxylase Homo sapiens 224-227 10356315-2 1999 For this reason, various indexes that measure plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr), as an expression of Phe metabolizing capacity, have been used for the detection of carriers for mutations in the PAH gene. Phenylalanine 131-134 phenylalanine hydroxylase Homo sapiens 224-227 10356315-7 1999 The results found show a relationship between the severity of PKU/HPA mutations in the PAH gene and their biochemical phenotype (Phe/Tyr, Phe2/Tyr) as an expression of the residual enzymatic activity. Phenylalanine 129-132 phenylalanine hydroxylase Homo sapiens 87-90 10037716-9 1999 In the presence of saturating (5 mM) concentrations of the substrate L-Phe, the paramagnetic molar relaxivity for human PAH decreased to 0.72 (+/- 0.05) x 10(3) s-1 M-1 with no significant change in the Ea. Phenylalanine 69-74 phenylalanine hydroxylase Homo sapiens 120-123 9860305-9 1998 Simple linear regression analysis showed a correlation between pretreatment phenylalanine concentrations and predicted PAH activity in 29 Japanese PKU patients (y=31.9-1.03x, r=0.59, P<0.0001). Phenylalanine 76-89 phenylalanine hydroxylase Homo sapiens 119-122 10331871-1 1999 Phenylalanine hydroxylase converts phenylalanine to tyrosine, a rate-limiting step in phenylalanine catabolism and protein and neurotransmitter biosynthesis. Phenylalanine 35-48 phenylalanine hydroxylase Homo sapiens 0-25 9642259-1 1998 Phenylalanine hydroxylase (PheOH) catalyzes the conversion of L-phenylalanine to L-tyrosine, the rate-limiting step in the oxidative degradation of phenylalanine. Phenylalanine 64-77 phenylalanine hydroxylase Homo sapiens 0-25 9700593-1 1998 The wide variation in phenylalanine hydroxylating capacity observed among patients with phenylketonuria (PKU) is primarily due to allelic heterogeneity at the phenylalanine hydroxylase (PAH) locus. Phenylalanine 22-35 phenylalanine hydroxylase Homo sapiens 159-184 9637722-2 1998 In phenylketonuria (PKU), the enzyme phenylalanine hydroxylase is deficient, resulting in a decreased conversion of phenylalanine (Phe) into tyrosine (Tyr). Phenylalanine 131-134 phenylalanine hydroxylase Homo sapiens 37-62 9686365-0 1998 Phenylalanine and tyrosine metabolism in phenylketonuria heterozygotes: influence of different phenylalanine hydroxylase mutations. Phenylalanine 0-13 phenylalanine hydroxylase Homo sapiens 95-120 9700593-1 1998 The wide variation in phenylalanine hydroxylating capacity observed among patients with phenylketonuria (PKU) is primarily due to allelic heterogeneity at the phenylalanine hydroxylase (PAH) locus. Phenylalanine 22-35 phenylalanine hydroxylase Homo sapiens 186-189 9700593-2 1998 In this study, we examined phenylalanine metabolism after an oral phenylalanine load in 148 carriers of known PAH gene mutations. Phenylalanine 27-40 phenylalanine hydroxylase Homo sapiens 110-113 9465044-0 1998 Identification of hepatic nuclear factor 1 binding sites in the 5" flanking region of the human phenylalanine hydroxylase gene: implication of a dual function of phenylalanine hydroxylase stimulator in the phenylalanine hydroxylation system. Phenylalanine 96-109 phenylalanine hydroxylase Homo sapiens 162-187 9465044-8 1998 This study suggests a possible dual function of PHS in vivo in the human phenylalanine hydroxylation system: it is involved in the regeneration of the cofactor tetrahydrobiopterin and can also enhance the expression of the human PAH gene. Phenylalanine 73-86 phenylalanine hydroxylase Homo sapiens 229-232 9204951-3 1997 This essential cofactor controls the production of L-tyrosine from L-phenylalanine via phenylalanine hydroxylase (PAH). Phenylalanine 67-82 phenylalanine hydroxylase Homo sapiens 87-112 9480820-3 1998 The latter event leads to an accumulation of the nonenzymatic isomer (7R) L-erythro 5,6,7,8 tetrahydrobiopterin (7BH4) inhibiting phenylalanine hydroxylase (PAH) with an apparent Ki = 10(-6) M. One consequence of decreased epidermal PAH activities would be a build-up of L-phenylalanine. Phenylalanine 271-286 phenylalanine hydroxylase Homo sapiens 130-155 9490012-5 1998 Our results also demonstrate that the conformational events involved in the activation of hPAH by its substrate (L-Phe) are mainly related to changes in the tertiary/quaternary structure. Phenylalanine 113-118 phenylalanine hydroxylase Homo sapiens 90-94 9792411-1 1998 Phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine; its activity is the major determinant of phenylalanine disposal. Phenylalanine 60-73 phenylalanine hydroxylase Homo sapiens 0-25 9792411-1 1998 Phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine; its activity is the major determinant of phenylalanine disposal. Phenylalanine 60-73 phenylalanine hydroxylase Homo sapiens 27-30 9792411-1 1998 Phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine; its activity is the major determinant of phenylalanine disposal. Phenylalanine 128-141 phenylalanine hydroxylase Homo sapiens 0-25 9792411-1 1998 Phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine; its activity is the major determinant of phenylalanine disposal. Phenylalanine 128-141 phenylalanine hydroxylase Homo sapiens 27-30 9380432-8 1997 The findings indicate that the in vivo metrical trait (phenylalanine oxidation rate) is not a simple equivalent of phenylalanine hydroxylation activity (unit of protein phenotype) and, as expected, is an emergent property under the control of more than the PAH locus. Phenylalanine 55-68 phenylalanine hydroxylase Homo sapiens 257-260