PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 26778769-1 2016 The role of oxidative stress (OXS) due to myocardial nitric oxide synthase (NOS) uncoupling related to oxidative depletion of its cofactor tetrahydrobiopterin (BH4) emerged in the pathogenesis of heart failure with preserved ejection fraction. sapropterin 139-158 nitric oxide synthase 2 Homo sapiens 53-74 26669076-1 2015 Tetrahydrobiopterin (BH4) is an essential cofactor for aromatic amino acid hydroxylases and all three nitric oxide synthase (NOS) isoforms. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 102-123 26669076-1 2015 Tetrahydrobiopterin (BH4) is an essential cofactor for aromatic amino acid hydroxylases and all three nitric oxide synthase (NOS) isoforms. sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 102-123 25139660-4 2014 NO is synthesized by NO synthase (NOS) with tetrahydrobiopterin (BH4) as the crucial cofactor. sapropterin 44-63 nitric oxide synthase 2 Homo sapiens 21-32 25764397-1 2015 Tetrahydrobiopterin (BH4) is a co-factor required for catalytic activity of nitric oxide synthase (NOS) and amino acid-monooxygenases, including phenylalanine hydroxylase. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 76-97 25764397-1 2015 Tetrahydrobiopterin (BH4) is a co-factor required for catalytic activity of nitric oxide synthase (NOS) and amino acid-monooxygenases, including phenylalanine hydroxylase. sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 76-97 25139660-4 2014 NO is synthesized by NO synthase (NOS) with tetrahydrobiopterin (BH4) as the crucial cofactor. sapropterin 65-68 nitric oxide synthase 2 Homo sapiens 21-32 24491428-4 2014 BH4 may also potentiate NMDA neurotransmission through its cofactor effect on nitric oxide synthase (NOS). sapropterin 0-3 nitric oxide synthase 2 Homo sapiens 78-99 23743404-1 2013 Functional constitutive nitric oxide synthase (NOS) and its cofactor tetrahydrobiopterin (BH4) are required for full reflex cutaneous vasodilation and are attenuated in primary aging. sapropterin 69-88 nitric oxide synthase 2 Homo sapiens 24-45 24180387-1 2014 Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS). sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 54-75 24180387-1 2014 Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS). sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 54-75 25548592-2 2014 Tetrahydrobiopterin (BH4) is a cofactor of nitric oxide synthase (NOS). sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 43-64 25548592-2 2014 Tetrahydrobiopterin (BH4) is a cofactor of nitric oxide synthase (NOS). sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 43-64 23743404-1 2013 Functional constitutive nitric oxide synthase (NOS) and its cofactor tetrahydrobiopterin (BH4) are required for full reflex cutaneous vasodilation and are attenuated in primary aging. sapropterin 90-93 nitric oxide synthase 2 Homo sapiens 24-45 23739137-2 2013 Recent evidence suggests that tetrahydrobiopterin (BH4), the cofactor of nitric oxide synthase (NOS), is involved in pulmonary hypertension and that pulmonary artery endothelial-to-mesenchymal transition (EnMT) may contribute to pulmonary fibrosis. sapropterin 30-49 nitric oxide synthase 2 Homo sapiens 73-94 24067187-8 2013 Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 to 0.14 at 6265 m), indicating lower NO availability resulting in less vasodilatative activity. sapropterin 18-37 nitric oxide synthase 2 Homo sapiens 61-82 24067187-8 2013 Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 to 0.14 at 6265 m), indicating lower NO availability resulting in less vasodilatative activity. sapropterin 39-42 nitric oxide synthase 2 Homo sapiens 61-82 23774601-6 2013 Treatment with gamma interferon (IFN-gamma), l-arginine, and tetrahydrobiopterin enhanced expression of NOS2 and NOS3 isoforms, as well as NO production. sapropterin 61-80 nitric oxide synthase 2 Homo sapiens 104-108 23739137-2 2013 Recent evidence suggests that tetrahydrobiopterin (BH4), the cofactor of nitric oxide synthase (NOS), is involved in pulmonary hypertension and that pulmonary artery endothelial-to-mesenchymal transition (EnMT) may contribute to pulmonary fibrosis. sapropterin 51-54 nitric oxide synthase 2 Homo sapiens 73-94 23385656-4 2013 An important question was if the oxidative environment experienced during diving limits the availability of the nitric oxide synthase (NOS) cofactor tetrahydrobiopterin (BH4). sapropterin 149-168 nitric oxide synthase 2 Homo sapiens 112-133 23385656-4 2013 An important question was if the oxidative environment experienced during diving limits the availability of the nitric oxide synthase (NOS) cofactor tetrahydrobiopterin (BH4). sapropterin 170-173 nitric oxide synthase 2 Homo sapiens 112-133 20846489-1 2010 Tetrahydrobiopterin (BH4) is a multifunctional cofactor of aromatic amino acid hydroxylases and nitric oxide synthase (NOS) as well as an intracellular antioxidant in animals. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 96-117 23241881-7 2013 Expression of GTP cyclohydrolase, which produces tetrahydrobiopterin (H(4)B), an essential cofactor for NOS2 homodimerization, increased after M stimulation in the presence or absence of AqH and NOS2 homodimers formed. sapropterin 49-68 nitric oxide synthase 2 Homo sapiens 104-108 23241881-7 2013 Expression of GTP cyclohydrolase, which produces tetrahydrobiopterin (H(4)B), an essential cofactor for NOS2 homodimerization, increased after M stimulation in the presence or absence of AqH and NOS2 homodimers formed. sapropterin 70-75 nitric oxide synthase 2 Homo sapiens 104-108 23241881-7 2013 Expression of GTP cyclohydrolase, which produces tetrahydrobiopterin (H(4)B), an essential cofactor for NOS2 homodimerization, increased after M stimulation in the presence or absence of AqH and NOS2 homodimers formed. sapropterin 70-75 nitric oxide synthase 2 Homo sapiens 195-199 23052970-1 2012 The cofactor tetrahydrobiopterin (BH4) is required for nitric oxide (NO) production by all nitric oxide synthase (NOS) enzymes and is a key regulator of cellular redox signalling. sapropterin 13-32 nitric oxide synthase 2 Homo sapiens 91-112 23052970-1 2012 The cofactor tetrahydrobiopterin (BH4) is required for nitric oxide (NO) production by all nitric oxide synthase (NOS) enzymes and is a key regulator of cellular redox signalling. sapropterin 34-37 nitric oxide synthase 2 Homo sapiens 91-112 23052970-6 2012 Leukocytes are a major site of iNOS expression, and the regulation of this isoform is another mechanism by which BH4 availability may modulate disease. sapropterin 113-116 nitric oxide synthase 2 Homo sapiens 31-35 21867484-1 2011 BH4 (6R-L-erythro-5,6,7,8-tetrahydrobiopterin) is an essential cofactor of a set of enzymes that are of central metabolic importance, including four aromatic amino acid hydroxylases, alkylglycerol mono-oxygenase and three NOS (NO synthase) isoenzymes. sapropterin 0-3 nitric oxide synthase 2 Homo sapiens 227-238 21867484-1 2011 BH4 (6R-L-erythro-5,6,7,8-tetrahydrobiopterin) is an essential cofactor of a set of enzymes that are of central metabolic importance, including four aromatic amino acid hydroxylases, alkylglycerol mono-oxygenase and three NOS (NO synthase) isoenzymes. sapropterin 5-45 nitric oxide synthase 2 Homo sapiens 227-238 23441062-0 2013 Tetrahydrobiopterin in nitric oxide synthase. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 23-44 21458460-1 2011 Tetrahydrobiopterin (BH(4)) is an essential cofactor for aromatic amino acid hydroxylases and for all three nitric oxide synthase (NOS) isoforms. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 108-129 21458460-1 2011 Tetrahydrobiopterin (BH(4)) is an essential cofactor for aromatic amino acid hydroxylases and for all three nitric oxide synthase (NOS) isoforms. sapropterin 21-26 nitric oxide synthase 2 Homo sapiens 108-129 20846489-1 2010 Tetrahydrobiopterin (BH4) is a multifunctional cofactor of aromatic amino acid hydroxylases and nitric oxide synthase (NOS) as well as an intracellular antioxidant in animals. sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 96-117 19294699-1 2009 GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme of a metabolic pathway synthesizing tetrahydrobiopterin (BH(4)), the cofactor dimerizing and activating inducible nitric oxide synthase (NOS-2). sapropterin 92-111 nitric oxide synthase 2 Homo sapiens 193-198 20669954-0 2010 Nitric oxide synthase stabilizes the tetrahydrobiopterin cofactor radical by controlling its protonation state. sapropterin 37-56 nitric oxide synthase 2 Homo sapiens 0-21 19932078-3 2010 Tetrahydrobiopterin (BH4)-replete iNOS was exposed to increasing concentrations of ROS/RNS and activity was measured with and without subsequent BH4 addition. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 34-38 19932078-3 2010 Tetrahydrobiopterin (BH4)-replete iNOS was exposed to increasing concentrations of ROS/RNS and activity was measured with and without subsequent BH4 addition. sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 34-38 19307452-1 2009 Tetrahydrobiopterin (BH(4)), a cofactor of inducible nitric-oxide synthase (iNOS), is an important post-translational regulator of NO bioactivity. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 43-74 19307452-1 2009 Tetrahydrobiopterin (BH(4)), a cofactor of inducible nitric-oxide synthase (iNOS), is an important post-translational regulator of NO bioactivity. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 76-80 18283102-1 2008 Nitric-oxide synthases (NOS) are catalytically self-sufficient flavo-heme enzymes that generate NO from arginine (Arg) and display a novel utilization of their tetrahydrobiopterin (H(4)B) cofactor. sapropterin 160-179 nitric oxide synthase 2 Homo sapiens 0-22 18582560-0 2009 WITHDRAWN: Roles of tetrahydrobiopterin (BH4) cofactor in nitric oxide synthase (NOS) catalysis. sapropterin 20-39 nitric oxide synthase 2 Homo sapiens 58-79 18582560-0 2009 WITHDRAWN: Roles of tetrahydrobiopterin (BH4) cofactor in nitric oxide synthase (NOS) catalysis. sapropterin 41-44 nitric oxide synthase 2 Homo sapiens 58-79 19059356-1 2009 Re-investigation of the electrochemical behavior of the nitric oxide synthase (NOS) cofactor tetrahydrobiopterin on graphite electrodes has revealed drastic differences in reversibility of electron transfer (ET) depending on the type of electrode surface employed. sapropterin 93-112 nitric oxide synthase 2 Homo sapiens 56-77 19319842-4 2009 The decreased NO generation results from a deficiency of (6R)-5,6,7,8-tetrahydrobiopterin [BH4; an essential cofactor for NO synthase (NOS)], as well as increased generation of glucosamine (an inhibitor of the pentose cycle for the production of NADPH, another cofactor for NOS) from glucose and L-glutamine. sapropterin 91-94 nitric oxide synthase 2 Homo sapiens 122-133 18372436-1 2008 GTP-cyclohydrolase 1 (GTP-CH1) catalyses the first and rate-limiting step for the de novo production of tetrahydrobiopterin (BH(4)), an essential cofactor for nitric oxide synthase (NOS). sapropterin 104-123 nitric oxide synthase 2 Homo sapiens 159-180 16946131-1 2006 Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, which are essential in the formation of neurotransmitters, and for nitric oxide synthase. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 160-181 17191137-2 2007 In addition, BH4 is now established to be an essential cofactor for all isoforms of nitric oxide synthase (NOS). sapropterin 13-16 nitric oxide synthase 2 Homo sapiens 84-105 17319660-1 2007 A quantum mechanical/molecular mechanical (QM/MM) study of the formation of the elusive active species Compound I (Cpd I) of nitric oxide synthase (NOS) from the oxyferrous intermediate shows that two protons have to be provided to produce a reaction that is reasonably exothermic and that leads to the appearance of a radical on the tetrahydrobiopterin cofactor. sapropterin 334-353 nitric oxide synthase 2 Homo sapiens 125-146 17448611-4 2007 It is proposed here that the switch involves a combination of two variable switches, the increase of nitric oxide synthase (NOS) activity and the partial uncoupling of the NOS activity, with uncoupling caused by a tetrahydrobiopterin (BH4) deficiency. sapropterin 235-238 nitric oxide synthase 2 Homo sapiens 101-122 18054268-1 2008 Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS). sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 55-76 18054268-1 2008 Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS). sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 55-76 16946131-1 2006 Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, which are essential in the formation of neurotransmitters, and for nitric oxide synthase. sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 160-181 16946131-4 2006 Such disorders exhibit BH4 depletion because of its oxidation and/or reduced synthesis, which can result in functional uncoupling of nitric oxide synthase (NOS). sapropterin 23-26 nitric oxide synthase 2 Homo sapiens 133-154 16641207-3 2006 GTP-cyclohydrolase 1 (GTP-CH1) is the rate-limiting enzyme for the biosynthesis of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) an essential cofactor for nitric oxide synthase (NOS) activity. sapropterin 83-123 nitric oxide synthase 2 Homo sapiens 156-177 16641207-3 2006 GTP-cyclohydrolase 1 (GTP-CH1) is the rate-limiting enzyme for the biosynthesis of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) an essential cofactor for nitric oxide synthase (NOS) activity. sapropterin 125-128 nitric oxide synthase 2 Homo sapiens 156-177 16702930-1 2006 BACKGROUND: It has recently been shown that tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase (NOS), reduces ischemia-reperfusion myocardial injury. sapropterin 44-63 nitric oxide synthase 2 Homo sapiens 96-117 16702930-1 2006 BACKGROUND: It has recently been shown that tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase (NOS), reduces ischemia-reperfusion myocardial injury. sapropterin 65-68 nitric oxide synthase 2 Homo sapiens 96-117 16172396-6 2005 iNOS localized to membrane fraction is predominantly monomeric, but dimerization is partially reconstituted rapidly upon incubation with tetrahydrobiopterin. sapropterin 137-156 nitric oxide synthase 2 Homo sapiens 0-4 16052472-0 2005 Roles of Ca2+ and the Ca2+-sensing receptor (CASR) in the expression of inducible NOS (nitric oxide synthase)-2 and its BH4 (tetrahydrobiopterin)-dependent activation in cytokine-stimulated adult human astrocytes. sapropterin 120-123 nitric oxide synthase 2 Homo sapiens 87-111 16052472-5 2005 However, NOS-2 activation is inhibited by NPS 89626 during the MEK/ERK-dependent stage between 24 and 24.5 h after adding the cytokines, and this inhibition can be overridden by exogenous BH4. sapropterin 188-191 nitric oxide synthase 2 Homo sapiens 9-14 16052472-6 2005 Therefore, NOS-2 expression and the subsequent BH4-dependent NOS-2-activation in human astrocytes need 1.8 mM Ca2+ to be in the culture medium, while NOS-2 activation also needs functional CASRs between 24 and 24.5 h after cytokine addition. sapropterin 47-50 nitric oxide synthase 2 Homo sapiens 11-16 16052472-6 2005 Therefore, NOS-2 expression and the subsequent BH4-dependent NOS-2-activation in human astrocytes need 1.8 mM Ca2+ to be in the culture medium, while NOS-2 activation also needs functional CASRs between 24 and 24.5 h after cytokine addition. sapropterin 47-50 nitric oxide synthase 2 Homo sapiens 61-66 16052472-6 2005 Therefore, NOS-2 expression and the subsequent BH4-dependent NOS-2-activation in human astrocytes need 1.8 mM Ca2+ to be in the culture medium, while NOS-2 activation also needs functional CASRs between 24 and 24.5 h after cytokine addition. sapropterin 47-50 nitric oxide synthase 2 Homo sapiens 61-66 16172396-8 2005 Depletion of intracellular tetrahydrobiopterin with an inhibitor of de novo pterin synthesis resulted in a predominance of monomeric iNOS without a greater relative distribution of iNOS to the peroxisomal pool. sapropterin 27-46 nitric oxide synthase 2 Homo sapiens 133-137 15933248-8 2005 Because BH4 is an essential cofactor for production of NO by both iNOS and endothelial nitric oxide synthase (eNOS), these results suggest that iNOS may reduce production of NO by eNOS by limiting availability of BH4. sapropterin 8-11 nitric oxide synthase 2 Homo sapiens 66-70 15933248-8 2005 Because BH4 is an essential cofactor for production of NO by both iNOS and endothelial nitric oxide synthase (eNOS), these results suggest that iNOS may reduce production of NO by eNOS by limiting availability of BH4. sapropterin 8-11 nitric oxide synthase 2 Homo sapiens 144-148 15933248-8 2005 Because BH4 is an essential cofactor for production of NO by both iNOS and endothelial nitric oxide synthase (eNOS), these results suggest that iNOS may reduce production of NO by eNOS by limiting availability of BH4. sapropterin 213-216 nitric oxide synthase 2 Homo sapiens 144-148 15933248-11 2005 CONCLUSIONS: We conclude that: (1) iNOS may impair contraction in part by activation of sGC; (2) iNOS impairs relaxation, at least in part, by limiting availability of BH4; and (3) expression of iNOS in endothelium may be a more important mediator of vascular dysfunction than expression of iNOS in adventitia. sapropterin 168-171 nitric oxide synthase 2 Homo sapiens 35-39 15933248-11 2005 CONCLUSIONS: We conclude that: (1) iNOS may impair contraction in part by activation of sGC; (2) iNOS impairs relaxation, at least in part, by limiting availability of BH4; and (3) expression of iNOS in endothelium may be a more important mediator of vascular dysfunction than expression of iNOS in adventitia. sapropterin 168-171 nitric oxide synthase 2 Homo sapiens 97-101 15933248-11 2005 CONCLUSIONS: We conclude that: (1) iNOS may impair contraction in part by activation of sGC; (2) iNOS impairs relaxation, at least in part, by limiting availability of BH4; and (3) expression of iNOS in endothelium may be a more important mediator of vascular dysfunction than expression of iNOS in adventitia. sapropterin 168-171 nitric oxide synthase 2 Homo sapiens 97-101 15933248-11 2005 CONCLUSIONS: We conclude that: (1) iNOS may impair contraction in part by activation of sGC; (2) iNOS impairs relaxation, at least in part, by limiting availability of BH4; and (3) expression of iNOS in endothelium may be a more important mediator of vascular dysfunction than expression of iNOS in adventitia. sapropterin 168-171 nitric oxide synthase 2 Homo sapiens 97-101 15565652-3 2005 The cytokines triggered a transient burst of p38 MAPK activity and the production of NOS-2 mRNA which were followed by bursts of MEK-ERK activities, synthesis of the NOS-2 co-factor tetrahydrobiopterin (BH(4)), a build-up of NOS-2 protein and from it active NOS-2 enzyme. sapropterin 182-201 nitric oxide synthase 2 Homo sapiens 166-171 15753231-4 2005 In this regard, substrate and cofactor availability play important roles in regulating nitric oxide synthase (NOS) activity not only by limiting enzyme activity but also by influencing the coupling of NOS with its cofactors, tetrahydrobiopterin and NADPH. sapropterin 225-244 nitric oxide synthase 2 Homo sapiens 87-108 15565652-3 2005 The cytokines triggered a transient burst of p38 MAPK activity and the production of NOS-2 mRNA which were followed by bursts of MEK-ERK activities, synthesis of the NOS-2 co-factor tetrahydrobiopterin (BH(4)), a build-up of NOS-2 protein and from it active NOS-2 enzyme. sapropterin 182-201 nitric oxide synthase 2 Homo sapiens 166-171 15565652-3 2005 The cytokines triggered a transient burst of p38 MAPK activity and the production of NOS-2 mRNA which were followed by bursts of MEK-ERK activities, synthesis of the NOS-2 co-factor tetrahydrobiopterin (BH(4)), a build-up of NOS-2 protein and from it active NOS-2 enzyme. sapropterin 182-201 nitric oxide synthase 2 Homo sapiens 166-171 16291253-1 2005 The role of tetrahydrobiopterin (BH4) as a cofactor in nitric oxide synthase (NOS) has been the object of intense research in the last few years. sapropterin 12-31 nitric oxide synthase 2 Homo sapiens 55-76 15471981-3 2005 If so, then is the mechanism because of intracellular depletion of tetrahydrobiopterin [BH4; a cofactor of NO synthase (NOS)], which results in superoxide production by uncoupled NOS? sapropterin 67-86 nitric oxide synthase 2 Homo sapiens 107-118 15471981-3 2005 If so, then is the mechanism because of intracellular depletion of tetrahydrobiopterin [BH4; a cofactor of NO synthase (NOS)], which results in superoxide production by uncoupled NOS? sapropterin 88-91 nitric oxide synthase 2 Homo sapiens 107-118 15290118-1 2005 PURPOSE: Tetrahydrobiopterin (BH4) is an essential co-factor for the synthesis of nitric oxide (NO), and BH4 deficiency may cause impaired NO synthase (NOS) activity. sapropterin 105-108 nitric oxide synthase 2 Homo sapiens 139-150 16244500-1 2005 Tetrahydrobiopterin (BH(4)) is a vital cofactor maintaining availability of the amine neurotransmitters [dopamine (DA), noradrenaline (NA), and serotonin (5-HT)], regulating the synthesis of nitric oxide (NO) by nitric oxide synthase (NOS), and stimulating and modulating the glutamatergic system (directly and indirectly). sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 212-233 16291253-1 2005 The role of tetrahydrobiopterin (BH4) as a cofactor in nitric oxide synthase (NOS) has been the object of intense research in the last few years. sapropterin 33-36 nitric oxide synthase 2 Homo sapiens 55-76 15537351-2 2004 The three aromatic amino acid hydroxylases (phenylalanine, tyrosine, and tryptophan hydroxylase) and nitric oxide synthase (NOS) all utilize (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)) as cofactor. sapropterin 141-183 nitric oxide synthase 2 Homo sapiens 101-122 15537351-2 2004 The three aromatic amino acid hydroxylases (phenylalanine, tyrosine, and tryptophan hydroxylase) and nitric oxide synthase (NOS) all utilize (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)) as cofactor. sapropterin 185-190 nitric oxide synthase 2 Homo sapiens 101-122 15219988-1 2004 Tetrahydrobiopterin (BH4) is an essential cofactor of nitric-oxide synthase (NOS) that serves as a 1-electron donor to the oxyferrous-heme complex. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 54-75 15219988-1 2004 Tetrahydrobiopterin (BH4) is an essential cofactor of nitric-oxide synthase (NOS) that serves as a 1-electron donor to the oxyferrous-heme complex. sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 54-75 14514694-0 2003 Single-turnover of nitric-oxide synthase in the presence of 4-amino-tetrahydrobiopterin: proposed role for tetrahydrobiopterin as a proton donor. sapropterin 68-87 nitric oxide synthase 2 Homo sapiens 19-40 15066989-1 2004 The catalytic center of nitric-oxide synthase (NOS) consists of a thiolate-coordinated heme macrocycle, a tetrahydrobiopterin (H4B) cofactor, and an l-arginine (l-Arg)/N-hydroxyarginine substrate binding site. sapropterin 106-125 nitric oxide synthase 2 Homo sapiens 24-45 14594819-8 2004 Thus, we show a differential effect of BH4 on NO release from eNOS and iNOS. sapropterin 39-42 nitric oxide synthase 2 Homo sapiens 71-75 15032648-7 2004 Experimental evidences suggest that (6R)-5,6,7,8-tetrahydrobiopterin (BH(4)), the natural and essential cofactor of NO synthases (NOS), plays a crucial role not only in increasing the rate of NO generation by NOS but also in controlling the formation of superoxide anion (O(2)(-)) in the endothelial cells. sapropterin 36-68 nitric oxide synthase 2 Homo sapiens 116-128 14514694-1 2003 Tetrahydrobiopterin (BH4) is an essential cofactor of nitric-oxide synthase (NOS) that serves as a one-electron donor to the oxyferrous.heme complex. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 54-75 14514694-1 2003 Tetrahydrobiopterin (BH4) is an essential cofactor of nitric-oxide synthase (NOS) that serves as a one-electron donor to the oxyferrous.heme complex. sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 54-75 12726922-1 2003 Tetrahydrobiopterin (BH4), which is an essential cofactor for nitric oxide synthase (NOS), is generally accepted as an important molecular target for oxidative stress. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 62-83 14609340-1 2003 Pterin-free inducible nitric oxide synthase (iNOS) was reconstituted with tetrahydrobiopterin (H(4)B) or tetrahydrobiopterin analogues (5-methyl-H(4)B and 4-amino-H(4)B), and the ability of bound 5-methyl-H(4)B and 4-amino-H(4)B to support catalysis by either full-length iNOS (FLiNOS) or the isolated heme domain (HDiNOS) was examined. sapropterin 74-93 nitric oxide synthase 2 Homo sapiens 45-49 14609340-1 2003 Pterin-free inducible nitric oxide synthase (iNOS) was reconstituted with tetrahydrobiopterin (H(4)B) or tetrahydrobiopterin analogues (5-methyl-H(4)B and 4-amino-H(4)B), and the ability of bound 5-methyl-H(4)B and 4-amino-H(4)B to support catalysis by either full-length iNOS (FLiNOS) or the isolated heme domain (HDiNOS) was examined. sapropterin 105-124 nitric oxide synthase 2 Homo sapiens 45-49 12883322-4 2003 Thus, treatment with DAHP and cytokines should lead to the intracellular accumulation of inactive inducible nitric oxide synthase (iNOS) apoenzyme (relative to BH4), which can be reactivated upon the repletion of BH4. sapropterin 213-216 nitric oxide synthase 2 Homo sapiens 98-129 12883322-4 2003 Thus, treatment with DAHP and cytokines should lead to the intracellular accumulation of inactive inducible nitric oxide synthase (iNOS) apoenzyme (relative to BH4), which can be reactivated upon the repletion of BH4. sapropterin 213-216 nitric oxide synthase 2 Homo sapiens 131-135 12883322-9 2003 Addition of BH4 or SEP substantially induced iNOS enzyme activity, which was quantified as the formation of [3H]L-citrulline from [3H]L-arginine. sapropterin 12-15 nitric oxide synthase 2 Homo sapiens 45-49 12726922-1 2003 Tetrahydrobiopterin (BH4), which is an essential cofactor for nitric oxide synthase (NOS), is generally accepted as an important molecular target for oxidative stress. sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 62-83 12726922-8 2003 These results suggest that H(2)O(2) induces BH4 synthesis via the induction of GTPCH, and the increased BH4 is coupled with NO production by coinduced iNOS. sapropterin 104-107 nitric oxide synthase 2 Homo sapiens 151-155 12414107-1 2002 Sepiapterin reductase (SPR) is the enzyme that catalyzes the final step of the synthesis of tetrahydrobiopterin (BH4), the cofactor for phenylalanine hydroxylase, tyrosine hydroxylase (TH), tryptophan hydroxylase, and nitric oxide synthase (NOS). sapropterin 113-116 nitric oxide synthase 2 Homo sapiens 218-239 12566086-0 2003 Diminished production of nitric oxide synthase cofactor tetrahydrobiopterin by rosiglitazone in adipocytes. sapropterin 56-75 nitric oxide synthase 2 Homo sapiens 25-46 12566086-3 2003 Our data indicate that modulated availability of the mandatory nitric oxide synthase (NOS) cofactor BH4 affected cytokine-induced NO generation. sapropterin 100-103 nitric oxide synthase 2 Homo sapiens 63-84 12667076-2 2003 N-Hydroxyguanidines interact with the oxygenase domain of BH(4)-free inducible NOS (BH(4)-free iNOS(oxy)), depending on the nature of their substituent, with formation of two types of complexes that are characterized by peaks around 395 (type I) and 438 nm (type II") during difference visible spectroscopy. sapropterin 58-63 nitric oxide synthase 2 Homo sapiens 95-99 12667076-3 2003 The complex formed between BH(4)-free iNOS(oxy) and N-benzyl-N"-hydroxyguanidine 1 (type II") exhibited a Soret peak at 430 nm, EPR signals at g = 1.93, 2.24, and 2.38, and RR bands at 1374 and 1502 cm(-)(1) that are characteristic of a low-spin hexacoordinated Fe(III) complex. sapropterin 27-32 nitric oxide synthase 2 Homo sapiens 38-42 12667076-10 2003 Interestingly, the K(s) values calculated for BH(4)-free iNOS(oxy)-N-hydroxyguanidine complexes were always lower when their substituents bore an aryl group (140-420 microM instead of 1000-3900 microM), suggesting the existence of pi-pi interactions between this group and an aromatic residue of the protein. sapropterin 46-51 nitric oxide synthase 2 Homo sapiens 57-61 12414107-1 2002 Sepiapterin reductase (SPR) is the enzyme that catalyzes the final step of the synthesis of tetrahydrobiopterin (BH4), the cofactor for phenylalanine hydroxylase, tyrosine hydroxylase (TH), tryptophan hydroxylase, and nitric oxide synthase (NOS). sapropterin 92-111 nitric oxide synthase 2 Homo sapiens 218-239 12214669-4 2002 By contrast, NO synthase (NOS) containing BH4 catalyze the selective monooxygenation of some N-hydroxyguanidines by NADPH and O2 with formation of NO and the corresponding ureas in a 1:1 molar ratio. sapropterin 42-45 nitric oxide synthase 2 Homo sapiens 13-24 12031711-10 2002 This event is essential for the induction of NO synthesis, which requires transcriptional induction of the genes that encode not only iNOS but also guanosine triphosphate cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in de novo BH4 synthesis. sapropterin 243-246 nitric oxide synthase 2 Homo sapiens 134-138 11051565-0 2000 The role of tetrahydrobiopterin in the activation of oxygen by nitric-oxide synthase. sapropterin 12-31 nitric oxide synthase 2 Homo sapiens 63-84 11514262-1 2001 Tetrahydrobiopterin is one of the most potent naturally occurring reducing agents and an essential cofactor required for enzymatic activity of nitric oxide synthase (NOS). sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 143-164 11292367-1 2001 Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), but its function is not fully understood. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 54-75 11292367-1 2001 Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase (NOS), but its function is not fully understood. sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 54-75 11181842-6 2001 Sepiapterin, a precursor of the nitric oxide synthase (NOS)-cofactor tetrahydrobiopterin also had a protective effect against anisomycin. sapropterin 69-88 nitric oxide synthase 2 Homo sapiens 32-53 10995244-0 2000 Low-temperature optical absorption spectra suggest a redox role for tetrahydrobiopterin in both steps of nitric oxide synthase catalysis. sapropterin 68-87 nitric oxide synthase 2 Homo sapiens 105-126 11815603-1 2002 In C6 glioma cells, the sphingolipid second messenger ceramide potentiates expression of inducible nitric-oxide synthase (iNOS) induced by tumor necrosis factor alpha (TNF-alpha) without affecting GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme in the biosynthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH(4)), a cofactor required for iNOS activity. sapropterin 275-307 nitric oxide synthase 2 Homo sapiens 89-120 11815603-1 2002 In C6 glioma cells, the sphingolipid second messenger ceramide potentiates expression of inducible nitric-oxide synthase (iNOS) induced by tumor necrosis factor alpha (TNF-alpha) without affecting GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme in the biosynthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH(4)), a cofactor required for iNOS activity. sapropterin 275-307 nitric oxide synthase 2 Homo sapiens 122-126 12003348-1 2002 Tetrahydrobiopterin (H4-biopterin) is an essential cofactor of a set of enzymes that are of central metabolic importance, i.e. the hydroxylases of the three aromatic amino acids phenylalanine, tyrosine, and tryptophan, of ether lipid oxidase, and of the three nitric oxide synthase (NOS) isoenzymes. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 260-281 12003348-1 2002 Tetrahydrobiopterin (H4-biopterin) is an essential cofactor of a set of enzymes that are of central metabolic importance, i.e. the hydroxylases of the three aromatic amino acids phenylalanine, tyrosine, and tryptophan, of ether lipid oxidase, and of the three nitric oxide synthase (NOS) isoenzymes. sapropterin 21-33 nitric oxide synthase 2 Homo sapiens 260-281 11730360-8 2001 We conclude that there are at least three mechanisms of synergistic cytokine-induced NO production: (1) the biosynthesis of iNOS monomer due to nonlinear interactions by transcription factors, (2) synergistic cytosolic activation of NF-kappaB, and (3) parallel biosynthesis of BH4 in the presence of cytokine combinations that include IL-1beta. sapropterin 277-280 nitric oxide synthase 2 Homo sapiens 124-128 11228398-3 2001 Since inducible NO synthase (iNOS) is known to be involved in the profound hypotension, we hypothesized that a decrease of tetrahydrobiopterin (BH(4)), an essential cofactor of iNOS, might account for the rapid effect of PMX-H on BP, if plasma BH(4) is increased concomitantly with NO in septic shock patients and if PMX can decrease BH(4). sapropterin 123-142 nitric oxide synthase 2 Homo sapiens 6-27 11228398-3 2001 Since inducible NO synthase (iNOS) is known to be involved in the profound hypotension, we hypothesized that a decrease of tetrahydrobiopterin (BH(4)), an essential cofactor of iNOS, might account for the rapid effect of PMX-H on BP, if plasma BH(4) is increased concomitantly with NO in septic shock patients and if PMX can decrease BH(4). sapropterin 123-142 nitric oxide synthase 2 Homo sapiens 29-33 11228398-3 2001 Since inducible NO synthase (iNOS) is known to be involved in the profound hypotension, we hypothesized that a decrease of tetrahydrobiopterin (BH(4)), an essential cofactor of iNOS, might account for the rapid effect of PMX-H on BP, if plasma BH(4) is increased concomitantly with NO in septic shock patients and if PMX can decrease BH(4). sapropterin 123-142 nitric oxide synthase 2 Homo sapiens 177-181 11587559-4 2001 The K(d) for arginine is approximately 0.5 microM for the tetrahydrobiopterin replete neuronal and inducible isoforms (nNOS and iNOS), while the endothelial isoform has a slightly higher K(d) (1.5 microM). sapropterin 58-77 nitric oxide synthase 2 Homo sapiens 128-132 10846172-0 2000 Aromatic residues and neighboring Arg414 in the (6R)-5,6,7, 8-tetrahydro-L-biopterin binding site of full-length neuronal nitric-oxide synthase are crucial in catalysis and heme reduction with NADPH. sapropterin 48-84 nitric oxide synthase 2 Homo sapiens 122-143 10846172-1 2000 Nitric-oxide synthase (NOS) requires the cofactor, (6R)-5,6,7, 8-tetrahydrobiopterin (H4B), for catalytic activity. sapropterin 51-84 nitric oxide synthase 2 Homo sapiens 0-21 10878285-10 2000 Third, by depleting guanosine nucleotides MPA also depletes tetrahydrobiopterin, a co-factor for the inducible form of nitric oxide synthase (iNOS). sapropterin 60-79 nitric oxide synthase 2 Homo sapiens 142-146 10788433-2 2000 Synthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH(4)), a required cofactor for inducible nitric-oxide synthase (iNOS) activity, is usually coordinately regulated with iNOS expression. sapropterin 13-45 nitric oxide synthase 2 Homo sapiens 79-110 10788433-2 2000 Synthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH(4)), a required cofactor for inducible nitric-oxide synthase (iNOS) activity, is usually coordinately regulated with iNOS expression. sapropterin 13-45 nitric oxide synthase 2 Homo sapiens 112-116 10788433-2 2000 Synthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH(4)), a required cofactor for inducible nitric-oxide synthase (iNOS) activity, is usually coordinately regulated with iNOS expression. sapropterin 13-45 nitric oxide synthase 2 Homo sapiens 167-171 10788433-4 2000 Expression of both iNOS and GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme in the BH(4) biosynthetic pathway, was also markedly increased, as were their activities and protein levels. sapropterin 90-95 nitric oxide synthase 2 Homo sapiens 19-23 10803847-3 2000 Like mammalian NOSs, carp iNOS protein contains putative binding sites for heme, tetrahydrobiopterin, calmodulin, flavine mononucleotide, flavine adenine dinucleotide, and NADPH. sapropterin 81-100 nitric oxide synthase 2 Homo sapiens 26-30 10666424-0 2000 Tetrahydrobiopterin improves endothelium-dependent vasodilation in chronic smokers : evidence for a dysfunctional nitric oxide synthase. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 114-135 10514451-0 1999 Reactivity of tetrahydrobiopterin bound to nitric-oxide synthase. sapropterin 14-33 nitric oxide synthase 2 Homo sapiens 43-64 10672847-1 2000 Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS) and a scavenger of oxygen-derived free radicals. sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 55-76 10672847-1 2000 Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS) and a scavenger of oxygen-derived free radicals. sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 55-76 10647995-5 2000 To alleviate this problem, cells of the U937 monocytoid line were engineered to express iNOS by transfection with human hepatic iNOS (DFGiNOS), leading to production of NO on supplementation with the cofactor tetrahydrobiopterin. sapropterin 209-228 nitric oxide synthase 2 Homo sapiens 88-92 10647995-5 2000 To alleviate this problem, cells of the U937 monocytoid line were engineered to express iNOS by transfection with human hepatic iNOS (DFGiNOS), leading to production of NO on supplementation with the cofactor tetrahydrobiopterin. sapropterin 209-228 nitric oxide synthase 2 Homo sapiens 128-132 10512739-1 1999 Subsaturating levels of tetrahydrobiopterin (BH(4)), an essential cofactor for nitric oxide synthase (NOS), can lead to endothelial dysfunction as a result of decreased production of nitric oxide. sapropterin 24-43 nitric oxide synthase 2 Homo sapiens 79-100 10514451-1 1999 Levels of tetrahydrobiopterin (BH(4)) bound to nitric-oxide synthase (NOS) were examined during multiple turnovers of the enzyme in the presence of an NADPH-regenerating system. sapropterin 10-29 nitric oxide synthase 2 Homo sapiens 47-68 10409685-5 1999 As in NOS-3, ZnS(4) plays a key role in stabilizing intersubunit contacts and in maintaining the integrity of the cofactor (tetrahydrobiopterin) binding site of NOS-2. sapropterin 124-143 nitric oxide synthase 2 Homo sapiens 161-166 12532822-2 1999 Tetrahydrobiopterin (BH4), a low molecular weight pterdine, is an essential cofactor required for the activity of NO synthase (NOS). sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 114-125 12532822-2 1999 Tetrahydrobiopterin (BH4), a low molecular weight pterdine, is an essential cofactor required for the activity of NO synthase (NOS). sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 114-125 10455901-4 1999 However, iNOS activity after gene transfer may be impaired by the availability of cofactor, such as tetrahydrobiopterin (BH4). sapropterin 100-119 nitric oxide synthase 2 Homo sapiens 9-13 10455901-4 1999 However, iNOS activity after gene transfer may be impaired by the availability of cofactor, such as tetrahydrobiopterin (BH4). sapropterin 121-124 nitric oxide synthase 2 Homo sapiens 9-13 10321973-3 1999 BH4 is a cofactor for three pteridine-requiring monooxygenases that hydroxylate aromatic L-amino acids, i.e., tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and phenylalanine hydroxylase (PAH), as well as for nitric oxide synthase (NOS). sapropterin 0-3 nitric oxide synthase 2 Homo sapiens 219-240 9858648-0 1998 Role of tetrahydrobiopterin in the function of nitric oxide synthase, and its cytoprotective effect (Review). sapropterin 8-27 nitric oxide synthase 2 Homo sapiens 47-68 9856817-0 1998 Induction of inducible nitric oxide synthase and its corresponding tetrahydrobiopterin-cofactor-synthesizing enzyme GTP-cyclohydrolase I during cutaneous wound repair. sapropterin 67-86 nitric oxide synthase 2 Homo sapiens 13-44 9856817-2 1998 In this study we investigated the regulation of inducible nitric oxide synthase (iNOS) and GTP-cyclohydrolase I (GTP-CH I), the rate-limiting enzyme in the biosynthesis of the iNOS cofactor (6R) 5,6,7,8-tetrahydrobiopterin (6-BH4), during the repair process. sapropterin 190-222 nitric oxide synthase 2 Homo sapiens 48-79 9856817-2 1998 In this study we investigated the regulation of inducible nitric oxide synthase (iNOS) and GTP-cyclohydrolase I (GTP-CH I), the rate-limiting enzyme in the biosynthesis of the iNOS cofactor (6R) 5,6,7,8-tetrahydrobiopterin (6-BH4), during the repair process. sapropterin 190-222 nitric oxide synthase 2 Homo sapiens 81-85 9856817-2 1998 In this study we investigated the regulation of inducible nitric oxide synthase (iNOS) and GTP-cyclohydrolase I (GTP-CH I), the rate-limiting enzyme in the biosynthesis of the iNOS cofactor (6R) 5,6,7,8-tetrahydrobiopterin (6-BH4), during the repair process. sapropterin 190-222 nitric oxide synthase 2 Homo sapiens 176-180 9914471-1 1999 In the present study we demonstrate that the 4-amino analogue of tetrahydrobiopterin, 2,4-diamino-5,6,7,8-tetrahydro-6-(l-erythro-1, 2-dihydroxypropyl)pteridine (4-amino-H4biopterin) binds with high affinity to recombinant endothelial NO synthase and concomitantly inhibits enzyme activity [IC50 = 14.8 +/- 7.5 microm in the presence of added 5,6,7,8-tetrahydro-l-erythrobiopterin (H4biopterin) 10 microm] as efficiently as previously shown for inducible NO synthase [Mayer, B., Wu, C.Q., Gorren, A.C.F., Pfeiffer, S., Schmidt, K., Clark, P., Stuehr, D.J. sapropterin 65-84 nitric oxide synthase 2 Homo sapiens 445-466 9914471-9 1999 (mg protein)-1], so that the selectivity of 4-amino-H4biopterin towards inducible NO synthase was not explained by differences in the H4biopterin levels. sapropterin 52-63 nitric oxide synthase 2 Homo sapiens 72-93 9858648-1 1998 This review discusses the role of (6R)-5,6,7,8-tetrahydrobiopterin (H4 biopterin) in the function of nitric oxide synthase (NOS), and the protective effect of H4 biopterin against nitric oxide (NO)- and/or reactive oxygen species-induced cytotoxicity. sapropterin 34-66 nitric oxide synthase 2 Homo sapiens 101-122 9858648-1 1998 This review discusses the role of (6R)-5,6,7,8-tetrahydrobiopterin (H4 biopterin) in the function of nitric oxide synthase (NOS), and the protective effect of H4 biopterin against nitric oxide (NO)- and/or reactive oxygen species-induced cytotoxicity. sapropterin 68-80 nitric oxide synthase 2 Homo sapiens 101-122 9367805-2 1997 Nitric oxide synthase (NOS) requires tetrahydrobiopterin (BH4) for activity. sapropterin 37-56 nitric oxide synthase 2 Homo sapiens 0-21 9405225-2 1997 The newly synthesized BH4 serves as a cofactor for optimal activity of inducible nitric oxide synthase (NOS2). sapropterin 22-25 nitric oxide synthase 2 Homo sapiens 104-108 9405225-3 1997 In human mesangial cells (HMC), BH4 is also a limiting factor for NOS2 expression. sapropterin 32-35 nitric oxide synthase 2 Homo sapiens 66-70 9668073-2 1998 Cytokine-inducible nitric-oxide (NO) synthase (iNOS) contains an oxygenase domain that binds heme, tetrahydrobiopterin, and L-arginine, and a reductase domain that binds FAD, FMN, calmodulin, and NADPH. sapropterin 99-118 nitric oxide synthase 2 Homo sapiens 47-51 9721014-1 1998 Biosynthesis of nitric oxide (NO) is performed by the dimeric, heme-containing enzyme nitric oxide synthase, which requires the flavins FAD and FMN, as well as the pteridine cofactor (6R)-5,6,7,8-tetrahydro-L-biopterin (H4biopterin) in order to catalyze the NADPH-dependent oxidation of L-arginine. sapropterin 220-231 nitric oxide synthase 2 Homo sapiens 86-107 9367805-2 1997 Nitric oxide synthase (NOS) requires tetrahydrobiopterin (BH4) for activity. sapropterin 58-61 nitric oxide synthase 2 Homo sapiens 0-21 9089781-1 1997 We have found in a previous study that 5-50 microM tetrahydrobiopterin (BH4) stimulated 1.2-2.5-fold Ca(2+)-dependent nitric-oxide synthase (NOS) activity in homogenates prepared from primordial human placentae. sapropterin 51-70 nitric oxide synthase 2 Homo sapiens 118-139 9173873-0 1997 Cysteine-200 of human inducible nitric oxide synthase is essential for dimerization of haem domains and for binding of haem, nitroarginine and tetrahydrobiopterin. sapropterin 143-162 nitric oxide synthase 2 Homo sapiens 22-53 9173873-7 1997 The iNOS 1-504 and 59-504 fusion proteins bound similar amounts of haem, Nomega-nitro-l-arginine (nitroarginine) and tetrahydrobiopterin, showing that the first 58 residues are not required for binding these factors. sapropterin 117-136 nitric oxide synthase 2 Homo sapiens 4-8 9089781-1 1997 We have found in a previous study that 5-50 microM tetrahydrobiopterin (BH4) stimulated 1.2-2.5-fold Ca(2+)-dependent nitric-oxide synthase (NOS) activity in homogenates prepared from primordial human placentae. sapropterin 72-75 nitric oxide synthase 2 Homo sapiens 118-139 8977400-5 1997 As demonstrated by reverse transcriptase-PCR analysis, IL-1 beta-stimulated NO generation was accompanied by a time-dependent increase in messenger RNA levels for iNOS and GTP-cyclohydrolase (GTPCH), the rate-limiting step for de novo tetrahydrobiopterin (BH4) biosynthesis. sapropterin 235-254 nitric oxide synthase 2 Homo sapiens 163-167 8977400-5 1997 As demonstrated by reverse transcriptase-PCR analysis, IL-1 beta-stimulated NO generation was accompanied by a time-dependent increase in messenger RNA levels for iNOS and GTP-cyclohydrolase (GTPCH), the rate-limiting step for de novo tetrahydrobiopterin (BH4) biosynthesis. sapropterin 256-259 nitric oxide synthase 2 Homo sapiens 163-167 8977400-8 1997 As BH4 is an essential cofactor for NOS catalytic activity, these observations strongly suggest that FSH-induced biosynthesis of endogenous BH4 is essential for full iNOS biosynthetic capacity in IL-1 beta-stimulated granulosa cells. sapropterin 140-143 nitric oxide synthase 2 Homo sapiens 166-170 8626754-0 1996 Reduction of quinonoid dihydrobiopterin to tetrahydrobiopterin by nitric oxide synthase. sapropterin 43-62 nitric oxide synthase 2 Homo sapiens 66-87 8755738-10 1996 These data taken together suggest that the L-arginine, dioxygen, and the BH4 binding sites are in close proximity in rH-iNOS. sapropterin 73-76 nitric oxide synthase 2 Homo sapiens 120-124 8616812-3 1996 This study demonstrates that argininosuccinate synthetase and GTP-cyclohydrolase-I, which catalyze rate-limiting steps in the synthesis of iNOS substrate (arginine) and cofactor (tetrahydrobiopterin), respectively, are coinduced with iNOS expression in two human tumor cell lines. sapropterin 179-198 nitric oxide synthase 2 Homo sapiens 139-143 8616812-3 1996 This study demonstrates that argininosuccinate synthetase and GTP-cyclohydrolase-I, which catalyze rate-limiting steps in the synthesis of iNOS substrate (arginine) and cofactor (tetrahydrobiopterin), respectively, are coinduced with iNOS expression in two human tumor cell lines. sapropterin 179-198 nitric oxide synthase 2 Homo sapiens 234-238 8631749-1 1996 Inducible nitric oxide (NO) synthase (iNOS) is comprised of an oxygenase domain containing heme, tetrahydrobiopterin, the substrate binding site, and a reductase domain containing FAD, FMN, calmodulin, and the NADPH binding site. sapropterin 97-116 nitric oxide synthase 2 Homo sapiens 38-42 8962079-1 1996 The nitric-oxide synthase (NOS; EC 1.14.13.39) reaction is formulated as a partially tetrahydrobiopterin (H4Bip)-dependent 5-electron oxidation of a terminal guanidino nitrogen of L-arginine (Arg) associated with stoichiometric consumption of dioxygen (O2) and 1.5 mol of NADPH to form L-citrulline (Cit) and nitric oxide (.NO). sapropterin 85-104 nitric oxide synthase 2 Homo sapiens 4-25 8662883-3 1996 We report here that BH4 is necessary not only for the activity but also for the expression of iNOS in human mesangial cells. sapropterin 20-23 nitric oxide synthase 2 Homo sapiens 94-98 8662883-4 1996 Inhibition of de novo BH4 synthesis with 2,4-diamino-6-hydroxypyrimidine (DAHP) significantly attenuated iNOS activity as well as mRNA and protein expression in response to interleukin 1beta plus tumor necrosis factor alpha (IL-1beta/TNF-alpha). sapropterin 22-25 nitric oxide synthase 2 Homo sapiens 105-109 8662883-8 1996 These results suggest that BH4 availability plays an important role in the regulation of iNOS expression. sapropterin 27-30 nitric oxide synthase 2 Homo sapiens 89-93 8662883-9 1996 The effect of BH4 appears to be mediated, at least in part, by an increase in mRNA stability, as indicated by the observation that DAHP shortened, whereas sepiapterin prolonged the half-life of IL-1beta/TNF-alpha-induced iNOS mRNA. sapropterin 14-17 nitric oxide synthase 2 Homo sapiens 221-225 8662883-10 1996 Taken together, our results suggest that the biosynthesis of BH4 contributes to cytokine induction of iNOS expression in human mesangial cells through the stabilization of iNOS mRNA. sapropterin 61-64 nitric oxide synthase 2 Homo sapiens 102-106 8662883-10 1996 Taken together, our results suggest that the biosynthesis of BH4 contributes to cytokine induction of iNOS expression in human mesangial cells through the stabilization of iNOS mRNA. sapropterin 61-64 nitric oxide synthase 2 Homo sapiens 172-176 8626754-1 1996 Rat cerebellar nitric oxide synthase (NOS) purified from transfected human kidney cells catalyzes an NADPHdependent reduction of quinonoid dihydrobiopterin (qBH2) to tetrahydrobiopterin (BH4). sapropterin 166-185 nitric oxide synthase 2 Homo sapiens 15-36 8626754-1 1996 Rat cerebellar nitric oxide synthase (NOS) purified from transfected human kidney cells catalyzes an NADPHdependent reduction of quinonoid dihydrobiopterin (qBH2) to tetrahydrobiopterin (BH4). sapropterin 187-190 nitric oxide synthase 2 Homo sapiens 15-36 8561501-5 1996 At 1 mM DAG and saturating BH4, half-times of inactivation of 0.7, 8, and 2 min were observed for the nNOS, eNOS, and iNOS isoforms, respectively. sapropterin 27-30 nitric oxide synthase 2 Homo sapiens 118-122 34513700-4 2021 5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthases (NOS) and aromatic amino acid hydroxylases, and its biosynthesis involves de novo biosynthesis and a pterin salvage pathway. sapropterin 0-27 nitric oxide synthase 2 Homo sapiens 63-85 7488039-1 1995 Tetrahydrobiopterin (BH4) is an essential cofactor for all three isoforms of nitric oxide synthase (NOS). sapropterin 0-19 nitric oxide synthase 2 Homo sapiens 77-98 7488039-1 1995 Tetrahydrobiopterin (BH4) is an essential cofactor for all three isoforms of nitric oxide synthase (NOS). sapropterin 21-24 nitric oxide synthase 2 Homo sapiens 77-98 7976184-2 1994 NO is generated enzymatically from L-arginine by a constitutive, cytosolic, Ca2+/calmodulin-activated NO synthase (NOS): NADPH- and tetrahydrobiopterin-dependent cytochrome P-450-type hemoprotein. sapropterin 132-151 nitric oxide synthase 2 Homo sapiens 102-113 8710815-3 1996 Chelation of Ca2+ in the medium abolishes the stimulatory effect, indicating that only a Ca2(+)-dependent NO-synthase (NOS) isoform is activated by BH4. sapropterin 148-151 nitric oxide synthase 2 Homo sapiens 106-117 7577932-1 1995 Nitric oxide synthases (NOS) require NADPH and tetrahydrobiopterin (H4biopterin) to convert L-arginine to L-citrulline. sapropterin 47-66 nitric oxide synthase 2 Homo sapiens 0-22 7577932-1 1995 Nitric oxide synthases (NOS) require NADPH and tetrahydrobiopterin (H4biopterin) to convert L-arginine to L-citrulline. sapropterin 68-79 nitric oxide synthase 2 Homo sapiens 0-22 7547858-2 1995 Trypsinolysis of iNOS inactivates its NO synthesis activity and cleaves the enzyme into a dimeric oxygenase fragment that contains heme, tetrahydrobiopterin, and the substrate binding site and a monomeric reductase fragment that contains FAD, FMN, calmodulin, and the binding site for NADPH [Ghosh, D. I., & Stuehr, D. H. (1995) Biochemistry 34, 801-807]. sapropterin 137-156 nitric oxide synthase 2 Homo sapiens 17-21 7530045-1 1995 Macrophage NO synthase (NOS) is a dimeric enzyme comprising two identical 130 kDa subunits and contains iron protoporphyrin IX (heme), tetrahydrobiopterin, FAD, FMN, and calmodulin. sapropterin 135-154 nitric oxide synthase 2 Homo sapiens 11-22 7514193-1 1994 Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity. sapropterin 14-33 nitric oxide synthase 2 Homo sapiens 61-82 8133311-4 1994 NO is formed from L-arginine by the enzyme NO synthase (NOS), for which tetrahydrobiopterin (BH4) is a necessary co-factor. sapropterin 72-91 nitric oxide synthase 2 Homo sapiens 43-54 8133311-4 1994 NO is formed from L-arginine by the enzyme NO synthase (NOS), for which tetrahydrobiopterin (BH4) is a necessary co-factor. sapropterin 93-96 nitric oxide synthase 2 Homo sapiens 43-54 7691806-2 1993 The cytokine-induced nitric oxide synthase (NOS) of macrophages is a homodimeric enzyme that contains iron protoporphorin IX (heme), FAD, FMN, tetrahydrobiopterin, and calmodulin. sapropterin 143-162 nitric oxide synthase 2 Homo sapiens 21-42 1358030-1 1992 (6R)-5,6,7,8-Tetrahydro-L-biopterin (R-THBP) is a cofactor not only for aromatic amino acid hydroxylases in mammalian tissues but also for nitric oxide synthase (NOS) induced by endotoxins or cytokines in some kinds of cells. sapropterin 0-35 nitric oxide synthase 2 Homo sapiens 139-160 1358030-1 1992 (6R)-5,6,7,8-Tetrahydro-L-biopterin (R-THBP) is a cofactor not only for aromatic amino acid hydroxylases in mammalian tissues but also for nitric oxide synthase (NOS) induced by endotoxins or cytokines in some kinds of cells. sapropterin 37-43 nitric oxide synthase 2 Homo sapiens 139-160 34513700-4 2021 5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthases (NOS) and aromatic amino acid hydroxylases, and its biosynthesis involves de novo biosynthesis and a pterin salvage pathway. sapropterin 29-32 nitric oxide synthase 2 Homo sapiens 63-85 35431403-2 2022 This manuscript takes a more systemic approach by examining how a marginal deficiency of tetrahydrobiopterin (BH4) resulting from mutations of the GCH1 (GTP cyclohydrolase 1) gene may result in the uncoupling of inducible Nitric Oxide Synthase (iNOS) early in the initial response of the innate immune system to SARS-CoV-2. sapropterin 89-108 nitric oxide synthase 2 Homo sapiens 245-249 35431403-2 2022 This manuscript takes a more systemic approach by examining how a marginal deficiency of tetrahydrobiopterin (BH4) resulting from mutations of the GCH1 (GTP cyclohydrolase 1) gene may result in the uncoupling of inducible Nitric Oxide Synthase (iNOS) early in the initial response of the innate immune system to SARS-CoV-2. sapropterin 110-113 nitric oxide synthase 2 Homo sapiens 245-249 31628042-1 2020 GTP cyclohydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS), and sepiapterin reductase (SR) are sequentially responsible for de novo synthesis of tetrahydrobiopterin (BH4), a known co-factor for nitric oxide synthase (NOS). sapropterin 159-178 nitric oxide synthase 2 Homo sapiens 208-229 32112882-0 2020 Correction of arginine metabolism with sepiapterin-the precursor of nitric oxide synthase cofactor BH4-induces immunostimulatory-shift of breast cancer. sapropterin 99-102 nitric oxide synthase 2 Homo sapiens 68-89 32112882-4 2020 We tested whether supplementing sepiapterin, the precursor of tetrahydrobiopterin (BH4)-the nitric oxide synthase (NOS) cofactor-redirects arginine metabolism from the pathway synthesizing polyamines to that of synthesizing nitric oxide (NO) and make breast tumors more immunogenic. sapropterin 62-81 nitric oxide synthase 2 Homo sapiens 92-113 32112882-4 2020 We tested whether supplementing sepiapterin, the precursor of tetrahydrobiopterin (BH4)-the nitric oxide synthase (NOS) cofactor-redirects arginine metabolism from the pathway synthesizing polyamines to that of synthesizing nitric oxide (NO) and make breast tumors more immunogenic. sapropterin 83-86 nitric oxide synthase 2 Homo sapiens 92-113 32574435-2 2020 A key co-factor for nitric oxide synthase (NOS), tetrahydrobiopterin (BH4), has been shown to be oxidized in vitro when exposed to hyperoxia. sapropterin 49-68 nitric oxide synthase 2 Homo sapiens 20-41 32574435-2 2020 A key co-factor for nitric oxide synthase (NOS), tetrahydrobiopterin (BH4), has been shown to be oxidized in vitro when exposed to hyperoxia. sapropterin 70-73 nitric oxide synthase 2 Homo sapiens 20-41 31454684-3 2019 The enzyme nitric oxide synthase (NOS), responsible for the production of nitric oxide (NO), when uncoupled is as a source of O2-, for example by the absence of its cofactor tetrahydrobiopterin (BH4). sapropterin 174-193 nitric oxide synthase 2 Homo sapiens 11-32 31454684-3 2019 The enzyme nitric oxide synthase (NOS), responsible for the production of nitric oxide (NO), when uncoupled is as a source of O2-, for example by the absence of its cofactor tetrahydrobiopterin (BH4). sapropterin 195-198 nitric oxide synthase 2 Homo sapiens 11-32