PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 20887755-5 2011 A pah(-) null mutant and an episomal complemented overexpressing derivative (pah-/+PAH) were readily obtained, and metabolic labeling studies established that PAH was required to hydroxylate Phe to Tyr. Phenylalanine 191-194 phenylalanine hydroxylase Mus musculus 77-80 22644647-1 2012 The Pah(enu1/enu2) (ENU1/2) mouse is a heteroallelic orthologous model displaying blood phenylalanine (Phe) concentrations characteristic of mild hyperphenylalaninemia. Phenylalanine 88-101 phenylalanine hydroxylase Mus musculus 4-7 22644647-1 2012 The Pah(enu1/enu2) (ENU1/2) mouse is a heteroallelic orthologous model displaying blood phenylalanine (Phe) concentrations characteristic of mild hyperphenylalaninemia. Phenylalanine 103-106 phenylalanine hydroxylase Mus musculus 4-7 22644647-4 2012 The administration of a single subcutaneous injection of l-Phe (1.1 mg l-Phe/g body weight) leads to an approximately twofold to threefold increase of blood Phe and phenylalanine/tyrosine (Phe/Tyr) ratio, and a 1.6-fold increase of both nonubiquitinated PAH protein content and PAH activity. Phenylalanine 57-62 phenylalanine hydroxylase Mus musculus 254-257 22644647-4 2012 The administration of a single subcutaneous injection of l-Phe (1.1 mg l-Phe/g body weight) leads to an approximately twofold to threefold increase of blood Phe and phenylalanine/tyrosine (Phe/Tyr) ratio, and a 1.6-fold increase of both nonubiquitinated PAH protein content and PAH activity. Phenylalanine 57-62 phenylalanine hydroxylase Mus musculus 278-281 22644647-4 2012 The administration of a single subcutaneous injection of l-Phe (1.1 mg l-Phe/g body weight) leads to an approximately twofold to threefold increase of blood Phe and phenylalanine/tyrosine (Phe/Tyr) ratio, and a 1.6-fold increase of both nonubiquitinated PAH protein content and PAH activity. Phenylalanine 59-62 phenylalanine hydroxylase Mus musculus 254-257 22644647-4 2012 The administration of a single subcutaneous injection of l-Phe (1.1 mg l-Phe/g body weight) leads to an approximately twofold to threefold increase of blood Phe and phenylalanine/tyrosine (Phe/Tyr) ratio, and a 1.6-fold increase of both nonubiquitinated PAH protein content and PAH activity. Phenylalanine 59-62 phenylalanine hydroxylase Mus musculus 278-281 22644647-9 2012 By boosting blood Phe concentrations, and by BH(4) supplementation, we have revealed novel insights into the processing and regulation of the ENU1/2-mutant PAH. Phenylalanine 18-21 phenylalanine hydroxylase Mus musculus 156-159 21917493-1 2011 Successful restoration of phenylalanine (Phe) clearance following liver-directed gene therapy in murine phenylketonuria (PKU) is likely dependent upon both the number of cells successfully transduced and the amount of phenylalanine hydroxylase (PAH) activity expressed per cell. Phenylalanine 26-39 phenylalanine hydroxylase Mus musculus 218-243 21917493-1 2011 Successful restoration of phenylalanine (Phe) clearance following liver-directed gene therapy in murine phenylketonuria (PKU) is likely dependent upon both the number of cells successfully transduced and the amount of phenylalanine hydroxylase (PAH) activity expressed per cell. Phenylalanine 41-44 phenylalanine hydroxylase Mus musculus 218-243 23867524-3 2013 Here we evaluated the ability of RBCs encapsulated with phenylalanine hydroxylase (PAH) to metabolize phenylalanine (Phe) from the blood and confer sustained enzymatic activity in the circulation. Phenylalanine 117-120 phenylalanine hydroxylase Mus musculus 56-81 20887755-5 2011 A pah(-) null mutant and an episomal complemented overexpressing derivative (pah-/+PAH) were readily obtained, and metabolic labeling studies established that PAH was required to hydroxylate Phe to Tyr. Phenylalanine 191-194 phenylalanine hydroxylase Mus musculus 159-162 20151201-7 2010 When transgenic PKU mice that constitutively expressed PAH in muscle were given intraperitoneal supplementation with BH(4), this produced (transient) effective clearance of Phe to normal levels. Phenylalanine 173-176 phenylalanine hydroxylase Mus musculus 55-58 20151201-8 2010 In addition, use of an AAV vector containing the genes for PAH, and for two key synthetic enzymes for BH(4), provided substantial and long-lasting correction (more than 1 year) of blood Phe levels when injected into skeletal muscle of PKU mice. Phenylalanine 186-189 phenylalanine hydroxylase Mus musculus 59-62 19916803-3 2010 Here, we report that liver PAH activity and phenylalanine clearance were also restored in PAH-deficient mice after simple intramuscular injection of either AAV2 pseudotype 1 (rAAV2/1) or rAAV2/8 vectors. Phenylalanine 44-57 phenylalanine hydroxylase Mus musculus 90-93 20943816-4 2010 An increase in phenylalanine metabolites is in agreement with the known regulation of the phenylalanine hydroxylase gene by Hnf1alpha. Phenylalanine 15-28 phenylalanine hydroxylase Mus musculus 90-115 17565982-11 2007 We also show that plasma phenylalanine levels were dramatically lowered in mice treated with PAH-based fusion proteins after intravenous administration. Phenylalanine 25-38 phenylalanine hydroxylase Mus musculus 93-96 19560382-9 2009 The degree of phosphorylation of PAH in the mutants and the state of activation (as measured by the 6MPH(4)/BH(4) activity ratio) increased as phenylalanine levels rose, and decreased when they fell. Phenylalanine 143-156 phenylalanine hydroxylase Mus musculus 33-36 19560382-11 2009 These studies provide in vivo evidence that phenylalanine concentration regulates the activity of PAH in the hph-1 mouse and that this acts via a mechanism that includes phosphorylation of the PAH molecule. Phenylalanine 44-57 phenylalanine hydroxylase Mus musculus 98-101 19560382-11 2009 These studies provide in vivo evidence that phenylalanine concentration regulates the activity of PAH in the hph-1 mouse and that this acts via a mechanism that includes phosphorylation of the PAH molecule. Phenylalanine 44-57 phenylalanine hydroxylase Mus musculus 193-196 18203898-1 2008 Phenylketonuria (PKU) is a genetic disorder caused by deficiency of phenylalanine hydroxylase (PAH) that requires life-long adherence to a low-phenylalanine (Phe) diet. Phenylalanine 0-3 phenylalanine hydroxylase Mus musculus 95-98 19172175-5 2009 Plasma levels of phenylalanine in homozygous (HMZ) PAH(enu2) mice were >12-fold those of heterozygous (HTZ) littermates while tyrosine levels were reduced. Phenylalanine 17-30 phenylalanine hydroxylase Mus musculus 51-54 16043102-1 2005 Phenylalanine homeostasis in mammals is primarily controlled by liver phenylalanine hydroxylase (PAH) activity. Phenylalanine 0-13 phenylalanine hydroxylase Mus musculus 70-95 17112485-8 2007 These neuropathologic changes were reversed following portal vein delivery of a recombinant adeno-associated virus-mouse phenylalanine hydroxylase-woodchuck hepatitis virus post-transcriptional response element (rAAV-mPAH-WPRE) vector to Pah(enu2) mice and corresponded to rapid reduction of serum Phe levels. Phenylalanine 298-301 phenylalanine hydroxylase Mus musculus 121-146 16043102-1 2005 Phenylalanine homeostasis in mammals is primarily controlled by liver phenylalanine hydroxylase (PAH) activity. Phenylalanine 0-13 phenylalanine hydroxylase Mus musculus 97-100 16043102-3 2005 A low level of residual liver PAH activity ensures near-normal dietary protein tolerance with normal serum phenylalanine level, but the precise threshold for normal phenylalanine clearance is unknown. Phenylalanine 107-120 phenylalanine hydroxylase Mus musculus 30-33 16043102-6 2005 Conversely, transplantation of PAH-positive hepatocytes into PAH-deficient Pah(enu2) mice, a model of human PKU, yielded a significant decrease in serum phenylalanine (<700 muM) when liver repopulation exceeded approximately 5%. Phenylalanine 153-166 phenylalanine hydroxylase Mus musculus 31-34 16043102-6 2005 Conversely, transplantation of PAH-positive hepatocytes into PAH-deficient Pah(enu2) mice, a model of human PKU, yielded a significant decrease in serum phenylalanine (<700 muM) when liver repopulation exceeded approximately 5%. Phenylalanine 153-166 phenylalanine hydroxylase Mus musculus 61-64 16043102-7 2005 These data suggest that restoration of phenylalanine homeostasis requires PAH activity in only a minority of hepatocytes. Phenylalanine 39-52 phenylalanine hydroxylase Mus musculus 74-77 15863237-2 2005 Phenylalanine hydroxylase (PAH) deficiency results in accumulation of phenylalanine (Phe) in the brain and leads to pathophysiological abnormalities including cognitive defect, if Phe diet is not restricted. Phenylalanine 70-83 phenylalanine hydroxylase Mus musculus 0-25 15925112-2 2005 Phenylalanine hydroxylase (PAH) mutations resulting reduced enzyme levels lead to accumulation of phenylalanine (Phe) in brain, if Phe diet is not restricted. Phenylalanine 98-111 phenylalanine hydroxylase Mus musculus 0-25 15925112-2 2005 Phenylalanine hydroxylase (PAH) mutations resulting reduced enzyme levels lead to accumulation of phenylalanine (Phe) in brain, if Phe diet is not restricted. Phenylalanine 98-111 phenylalanine hydroxylase Mus musculus 27-30 15925112-2 2005 Phenylalanine hydroxylase (PAH) mutations resulting reduced enzyme levels lead to accumulation of phenylalanine (Phe) in brain, if Phe diet is not restricted. Phenylalanine 0-3 phenylalanine hydroxylase Mus musculus 27-30 15925112-2 2005 Phenylalanine hydroxylase (PAH) mutations resulting reduced enzyme levels lead to accumulation of phenylalanine (Phe) in brain, if Phe diet is not restricted. Phenylalanine 113-116 phenylalanine hydroxylase Mus musculus 0-25 15925112-2 2005 Phenylalanine hydroxylase (PAH) mutations resulting reduced enzyme levels lead to accumulation of phenylalanine (Phe) in brain, if Phe diet is not restricted. Phenylalanine 113-116 phenylalanine hydroxylase Mus musculus 27-30 15946242-2 2005 Circulating phenylalanine is normally cleared by phenylalanine hydroxylase (PAH) expressed in the liver. Phenylalanine 12-25 phenylalanine hydroxylase Mus musculus 49-74 15863237-2 2005 Phenylalanine hydroxylase (PAH) deficiency results in accumulation of phenylalanine (Phe) in the brain and leads to pathophysiological abnormalities including cognitive defect, if Phe diet is not restricted. Phenylalanine 85-88 phenylalanine hydroxylase Mus musculus 0-25 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 Mus musculus 118-121 15464429-1 2004 We previously proposed a novel disease entity, tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase (PAH) deficiency, in which administration of BH4 reduced elevated levels of serum phenylalanine [J. Pediatr. Phenylalanine 84-97 phenylalanine hydroxylase Mus musculus 111-114 8828602-5 1996 In contrast, a vector derived from a recombinant adenovirus can restore 10%-80% of normal hepatic PAH activity into PAH-deficient mice, which completely normalizes serum phenylalanine levels. Phenylalanine 170-183 phenylalanine hydroxylase Mus musculus 116-119 8965095-1 1996 Phenylketonuria (PKU) is caused by mutation(s) in the phenylalanine hydroxylase (PAH) gene which lead to deficient PAH activity and an accumulation of phenylalanine in the blood. Phenylalanine 54-67 phenylalanine hydroxylase Mus musculus 81-84 8965095-1 1996 Phenylketonuria (PKU) is caused by mutation(s) in the phenylalanine hydroxylase (PAH) gene which lead to deficient PAH activity and an accumulation of phenylalanine in the blood. Phenylalanine 54-67 phenylalanine hydroxylase Mus musculus 115-118 1321825-1 1992 Human phenylalanine hydroxylase (PAH) catalyzes the conversion of L-phenylalanine to L-tyrosine. Phenylalanine 66-81 phenylalanine hydroxylase Mus musculus 6-31 7584088-4 1994 Although this therapeutic effect did not persist, analysis of the relationship between hepatic PAH activity and serum phenylalanine levels indicated that only 10-20% of normal enzymatic activity in the mouse liver is sufficient to restore normal serum phenylalanine levels. Phenylalanine 118-131 phenylalanine hydroxylase Mus musculus 95-98 1321825-1 1992 Human phenylalanine hydroxylase (PAH) catalyzes the conversion of L-phenylalanine to L-tyrosine. Phenylalanine 66-81 phenylalanine hydroxylase Mus musculus 33-36 1312261-5 1992 The PAH mRNA was translated efficiently into PAH protein that is capable of converting phenylalanine to tyrosine in vitro. Phenylalanine 87-100 phenylalanine hydroxylase Mus musculus 4-7 1312261-5 1992 The PAH mRNA was translated efficiently into PAH protein that is capable of converting phenylalanine to tyrosine in vitro. Phenylalanine 87-100 phenylalanine hydroxylase Mus musculus 45-48 6476382-5 1984 The KM and Vmax values of both phenylalanine and 6-methyl-5,6,7,8-tetrahydropterin were determined for mouse liver phenylalanine hydroxylase. Phenylalanine 31-44 phenylalanine hydroxylase Mus musculus 115-140 35356682-2 2022 Mutations in the phenylalanine hydroxylase (PAH) gene are the main cause of the disease whose signature hallmarks of toxically elevated levels of Phe accumulation in plasma and organs such as the brain, result in irreversible intellectual disability. Phenylalanine 146-149 phenylalanine hydroxylase Mus musculus 17-42 35356682-2 2022 Mutations in the phenylalanine hydroxylase (PAH) gene are the main cause of the disease whose signature hallmarks of toxically elevated levels of Phe accumulation in plasma and organs such as the brain, result in irreversible intellectual disability. Phenylalanine 146-149 phenylalanine hydroxylase Mus musculus 44-47 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 Mus musculus 147-150 3741696-6 1986 Feeding phenylalanine alone also led to decreased activity of phenylalanine hydroxylase and increased concentration of Phe in serum. Phenylalanine 8-21 phenylalanine hydroxylase Mus musculus 62-87 33824313-1 2021 Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH), leading to systemic accumulation of L-phenylalanine (L-Phe) that may reach neurotoxic levels. Phenylalanine 136-151 phenylalanine hydroxylase Mus musculus 67-92 33824313-1 2021 Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH), leading to systemic accumulation of L-phenylalanine (L-Phe) that may reach neurotoxic levels. Phenylalanine 136-151 phenylalanine hydroxylase Mus musculus 94-97 33824313-1 2021 Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH), leading to systemic accumulation of L-phenylalanine (L-Phe) that may reach neurotoxic levels. Phenylalanine 153-158 phenylalanine hydroxylase Mus musculus 67-92 33824313-1 2021 Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH), leading to systemic accumulation of L-phenylalanine (L-Phe) that may reach neurotoxic levels. Phenylalanine 153-158 phenylalanine hydroxylase Mus musculus 94-97 33824313-2 2021 A homozygous Pah-R261Q mouse, with a highly prevalent misfolding variant in humans, reveals the expected hepatic PAH activity decrease, systemic L-Phe increase, L-tyrosine and L-tryptophan decrease, and tetrahydrobiopterin-responsive hyperphenylalaninemia. Phenylalanine 145-150 phenylalanine hydroxylase Mus musculus 13-16 34819582-1 2021 Phenylketonuria (PKU) is a genetic deficiency of phenylalanine hydroxylase (PAH) in liver resulting in blood phenylalanine (Phe) elevation and neurotoxicity. Phenylalanine 109-122 phenylalanine hydroxylase Mus musculus 76-79 34819582-1 2021 Phenylketonuria (PKU) is a genetic deficiency of phenylalanine hydroxylase (PAH) in liver resulting in blood phenylalanine (Phe) elevation and neurotoxicity. Phenylalanine 124-127 phenylalanine hydroxylase Mus musculus 76-79 34819582-10 2021 Taken together, here we show that blood Phe lowering strategy using PAH or PAL corrects both brain pathology as well as previously unknown lipid metabolism associated pathway changes in liver. Phenylalanine 40-43 phenylalanine hydroxylase Mus musculus 68-71 35600090-1 2022 Phenylketonuria (PKU) is a genetic disorder affecting around 1 in 12,000 live births (1), caused by a mutation in the phenylalanine hydroxylase (PAH) gene in the liver which facilitates the catabolism of phenylalanine (Phe). Phenylalanine 204-217 phenylalanine hydroxylase Mus musculus 118-143 35600090-1 2022 Phenylketonuria (PKU) is a genetic disorder affecting around 1 in 12,000 live births (1), caused by a mutation in the phenylalanine hydroxylase (PAH) gene in the liver which facilitates the catabolism of phenylalanine (Phe). Phenylalanine 204-217 phenylalanine hydroxylase Mus musculus 145-148 35600090-1 2022 Phenylketonuria (PKU) is a genetic disorder affecting around 1 in 12,000 live births (1), caused by a mutation in the phenylalanine hydroxylase (PAH) gene in the liver which facilitates the catabolism of phenylalanine (Phe). Phenylalanine 219-222 phenylalanine hydroxylase Mus musculus 118-143 35600090-1 2022 Phenylketonuria (PKU) is a genetic disorder affecting around 1 in 12,000 live births (1), caused by a mutation in the phenylalanine hydroxylase (PAH) gene in the liver which facilitates the catabolism of phenylalanine (Phe). Phenylalanine 219-222 phenylalanine hydroxylase Mus musculus 145-148 7150251-1 1982 A prolonged elevation in the concentrations of circulating phenylalanine was maintained in newborn mice by daily injections of phenylalanine and a phenylalanine hydroxylase inhibitor, alpha-methylphenylalanine. Phenylalanine 59-72 phenylalanine hydroxylase Mus musculus 147-172 33896013-4 2021 Dose-dependent transduction of the liver and expression of PAH mRNA were present with both vectors, resulting in significant and durable reduction of circulating phenylalanine, reaching near control levels in males. Phenylalanine 162-175 phenylalanine hydroxylase Mus musculus 59-62 153135-1 1978 The phenylalanine analogues p-chlorophenylalanine and alpha-methylphenylalanine were used to inhibit phenylalanine hydroxylase in animal models for phenylketonuria. Phenylalanine 4-17 phenylalanine hydroxylase Mus musculus 101-126 566796-4 1977 The significantly higher phenylalanine level and phenylalanine/tyrosine ratio in the liver of 20-day-old "dl" mice suggest a lower liver phenylalanine hydroxylase activity. Phenylalanine 25-38 phenylalanine hydroxylase Mus musculus 137-162 29514280-2 2018 The hepatic phenylalanine hydroxylating system is regulated by the ratio of l-phenylalanine, which is substrate of phenylalanine hydroxylase (PAH), to the PAH cofactor tetrahydrobiopterin (BH4). Phenylalanine 12-25 phenylalanine hydroxylase Mus musculus 115-140 29514280-2 2018 The hepatic phenylalanine hydroxylating system is regulated by the ratio of l-phenylalanine, which is substrate of phenylalanine hydroxylase (PAH), to the PAH cofactor tetrahydrobiopterin (BH4). Phenylalanine 12-25 phenylalanine hydroxylase Mus musculus 142-145 29514280-2 2018 The hepatic phenylalanine hydroxylating system is regulated by the ratio of l-phenylalanine, which is substrate of phenylalanine hydroxylase (PAH), to the PAH cofactor tetrahydrobiopterin (BH4). Phenylalanine 12-25 phenylalanine hydroxylase Mus musculus 155-158 29514280-2 2018 The hepatic phenylalanine hydroxylating system is regulated by the ratio of l-phenylalanine, which is substrate of phenylalanine hydroxylase (PAH), to the PAH cofactor tetrahydrobiopterin (BH4). Phenylalanine 76-91 phenylalanine hydroxylase Mus musculus 115-140 29514280-2 2018 The hepatic phenylalanine hydroxylating system is regulated by the ratio of l-phenylalanine, which is substrate of phenylalanine hydroxylase (PAH), to the PAH cofactor tetrahydrobiopterin (BH4). Phenylalanine 76-91 phenylalanine hydroxylase Mus musculus 142-145 29514280-8 2018 Interference of PAH protein misfolding with metabolite-based control of l-phenylalanine turnover suggests a mechanistic link between perturbation of protein homeostasis and disturbed regulation of metabolic pathways. Phenylalanine 72-87 phenylalanine hydroxylase Mus musculus 16-19 26822703-5 2016 The PAH(enu2) mouse models human PKU with intrinsic hyperphenylalaninemia, abnormal response to Phe challenge, and neurologic deficit. Phenylalanine 96-99 phenylalanine hydroxylase Mus musculus 4-7 28520731-1 2017 Phenylketonuria (PKU) is a genetic disease characterized by the inability to convert dietary phenylalanine to tyrosine by phenylalanine hydroxylase. Phenylalanine 93-106 phenylalanine hydroxylase Mus musculus 122-147 27091224-1 2016 High phenylalanine concentrations in the brain due to dysfunctional phenylalanine hydroxylase (Pah) are considered to account for mental retardation in phenylketonuria (PKU). Phenylalanine 5-18 phenylalanine hydroxylase Mus musculus 95-98 25296915-3 2015 Mutations of the Pah gene in Pah(enu2)/c57bl6 mice result in elevated levels of phenylalanine in serum similar to those in humans suffering from PKU. Phenylalanine 80-93 phenylalanine hydroxylase Mus musculus 17-20 25664353-3 2015 The synthesis of Tyr from Phe requires the presence of tetrahydrobiopterin (BH4) as a cofactor of phenylalanine hydroxylase (PAH). Phenylalanine 26-29 phenylalanine hydroxylase Mus musculus 98-123 25296915-3 2015 Mutations of the Pah gene in Pah(enu2)/c57bl6 mice result in elevated levels of phenylalanine in serum similar to those in humans suffering from PKU. Phenylalanine 80-93 phenylalanine hydroxylase Mus musculus 29-32