biopterin

Summary

Summary: A natural product that has been considered as a growth factor for some insects.

Top Publications

  1. ncbi Altered tetrahydrobiopterin metabolism in atherosclerosis: implications for use of oxidized tetrahydrobiopterin analogues and thiol antioxidants
    Jeannette Vasquez-Vivar
    Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, USA
    Arterioscler Thromb Vasc Biol 22:1655-61. 2002
  2. pmc Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension
    Ulf Landmesser
    Division of Cardiology, Emory University School of Medicine and Atlanta Veterans Administration Hospital, 1639 Pierce Drive, Atlanta, GA 30322, USA
    J Clin Invest 111:1201-9. 2003
  3. ncbi Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase
    Nermin Kuzkaya
    Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 278:22546-54. 2003
  4. doi Tetrahydrobiopterin: biochemistry and pathophysiology
    Ernst R Werner
    Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck A 6020, Austria
    Biochem J 438:397-414. 2011
  5. pmc Tetrahydrobiopterin biosynthesis, regeneration and functions
    B Thony
    Division of Clinical Chemistry, University Children s Hospital, Steinwiesstrasse 75, 8032 Zurich, Switzerland
    Biochem J 347:1-16. 2000
  6. ncbi Proteasome-dependent degradation of guanosine 5'-triphosphate cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes mellitus
    Jian Xu
    Division of Endocrinology and Diabetes, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Circulation 116:944-53. 2007
  7. ncbi Stoichiometric relationships between endothelial tetrahydrobiopterin, endothelial NO synthase (eNOS) activity, and eNOS coupling in vivo: insights from transgenic mice with endothelial-targeted GTP cyclohydrolase 1 and eNOS overexpression
    Jennifer K Bendall
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom
    Circ Res 97:864-71. 2005
  8. ncbi Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease
    Nicholas J Alp
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
    Arterioscler Thromb Vasc Biol 24:413-20. 2004
  9. pmc The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide synthase: an EPR spin trapping study
    Jeannette Vasquez-Vivar
    Biophysics Research Institute and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, U S A
    Biochem J 362:733-9. 2002
  10. pmc Identification of the gene encoding alkylglycerol monooxygenase defines a third class of tetrahydrobiopterin-dependent enzymes
    Katrin Watschinger
    Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz Pregl Strasse 3, A 6020 Innsbruck, Austria
    Proc Natl Acad Sci U S A 107:13672-7. 2010

Detail Information

Publications255 found, 100 shown here

  1. ncbi Altered tetrahydrobiopterin metabolism in atherosclerosis: implications for use of oxidized tetrahydrobiopterin analogues and thiol antioxidants
    Jeannette Vasquez-Vivar
    Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, USA
    Arterioscler Thromb Vasc Biol 22:1655-61. 2002
    ..The purpose of this study was to investigate the effects of hyperlipidemia on vascular BH4 levels and the effect of supplementation with sepiapterin in the presence and absence of N-acetylcysteine (NAC)...
  2. pmc Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension
    Ulf Landmesser
    Division of Cardiology, Emory University School of Medicine and Atlanta Veterans Administration Hospital, 1639 Pierce Drive, Atlanta, GA 30322, USA
    J Clin Invest 111:1201-9. 2003
    ..Treatment strategies that increase tetrahydrobiopterin or prevent its oxidation may prove useful in preventing vascular complications of this common disease...
  3. ncbi Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase
    Nermin Kuzkaya
    Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 278:22546-54. 2003
    ..We confirmed that ONOO- uncouples eNOS by oxidation of tetrahydrobiopterin and that ascorbate does not fully protect BH4 from oxidation but recycles BH3. radical back to BH4...
  4. doi Tetrahydrobiopterin: biochemistry and pathophysiology
    Ernst R Werner
    Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck A 6020, Austria
    Biochem J 438:397-414. 2011
    ....
  5. pmc Tetrahydrobiopterin biosynthesis, regeneration and functions
    B Thony
    Division of Clinical Chemistry, University Children s Hospital, Steinwiesstrasse 75, 8032 Zurich, Switzerland
    Biochem J 347:1-16. 2000
    ..Furthermore, several neurological diseases, including Dopa-responsive dystonia, but also Alzheimer's disease, Parkinson's disease, autism and depression, have been suggested to be a consequence of restricted cofactor availability...
  6. ncbi Proteasome-dependent degradation of guanosine 5'-triphosphate cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes mellitus
    Jian Xu
    Division of Endocrinology and Diabetes, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Circulation 116:944-53. 2007
    ....
  7. ncbi Stoichiometric relationships between endothelial tetrahydrobiopterin, endothelial NO synthase (eNOS) activity, and eNOS coupling in vivo: insights from transgenic mice with endothelial-targeted GTP cyclohydrolase 1 and eNOS overexpression
    Jennifer K Bendall
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom
    Circ Res 97:864-71. 2005
    ..These data indicate that eNOS coupling is directly related to eNOS-BH4 stoichiometry even in the absence of a vascular disease state. Endothelial BH4 availability is a pivotal regulator of eNOS activity and enzymatic coupling in vivo...
  8. ncbi Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease
    Nicholas J Alp
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
    Arterioscler Thromb Vasc Biol 24:413-20. 2004
    ..Thus, BH4 represents a potential therapeutic target in the regulation of eNOS function in vascular disease...
  9. pmc The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide synthase: an EPR spin trapping study
    Jeannette Vasquez-Vivar
    Biophysics Research Institute and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, U S A
    Biochem J 362:733-9. 2002
    ..NO formation. Collectively, these results indicate that the ratio between oxidized and reduced BH(4) metabolites tightly regulates superoxide formation from eNOS. The pathological significance of this scenario is discussed...
  10. pmc Identification of the gene encoding alkylglycerol monooxygenase defines a third class of tetrahydrobiopterin-dependent enzymes
    Katrin Watschinger
    Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz Pregl Strasse 3, A 6020 Innsbruck, Austria
    Proc Natl Acad Sci U S A 107:13672-7. 2010
    ..This sequence assignment suggests that alkylglycerol monooxygenase forms a distinct third group among tetrahydrobiopterin-dependent enzymes...
  11. pmc Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways
    Mark J Crabtree
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
    J Biol Chem 284:28128-36. 2009
    ..In contrast to the decreased BH4:BH2 ratio induced by DHFR knockdown, GTPCH knockdown greatly reduced total biopterin levels but with no change in BH4:BH2 ratio...
  12. pmc Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression
    Nicholas J Alp
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffr Hospital, United Kingdom
    J Clin Invest 112:725-35. 2003
    ..streptozotocin (STZ) increased vascular oxidative stress, resulting in oxidative loss of BH4, forming BH2 and biopterin. Endothelial cell superoxide production in diabetes was increased, and NO-mediated endothelium-dependent ..
  13. pmc Myocardial ischemia results in tetrahydrobiopterin (BH4) oxidation with impaired endothelial function ameliorated by BH4
    Cristian Dumitrescu
    Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 104:15081-6. 2007
    ..Supplementation of BH(4) may therefore be an important therapeutic approach to reverse endothelial dysfunction in postischemic tissues...
  14. doi Quantitative regulation of intracellular endothelial nitric-oxide synthase (eNOS) coupling by both tetrahydrobiopterin-eNOS stoichiometry and biopterin redox status: insights from cells with tet-regulated GTP cyclohydrolase I expression
    Mark J Crabtree
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
    J Biol Chem 284:1136-44. 2009
    ..Doxycycline abolished GTPCH mRNA expression and GTPCH protein, leading to markedly diminished total biopterin levels and a decreased ratio of BH4 to oxidized biopterins in cells expressing eNOS...
  15. pmc Reduced infectivity of a Leishmania donovani biopterin transporter genetic mutant and its use as an attenuated strain for vaccination
    Barbara Papadopoulou
    Centre de Recherche en Infectiologie du Centre de Recherche du CHUL and Division de Microbiologie, Faculte de Medecine, Universite Laval, Quebec, Canada
    Infect Immun 70:62-8. 2002
    Pterins are essential for the growth of Leishmania species, and recent work has led to the isolation of the biopterin transporter BT1...
  16. ncbi Correction of endothelial dysfunction in diabetic female rats by tetrahydrobiopterin and chronic insulin
    Eliana H Akamine
    Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
    J Vasc Res 43:309-20. 2006
    ..Our data suggest that, similarly to males, endothelial dysfunction in female diabetic rats involves an altered ROS/NO imbalance. In contrast to males, however, insulin does not regulate NOS in the microcirculation of diabetic females...
  17. doi Systemic and vascular oxidation limits the efficacy of oral tetrahydrobiopterin treatment in patients with coronary artery disease
    Colin Cunnington
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
    Circulation 125:1356-66. 2012
    ..We sought to determine the mechanisms relating exogenous BH4 to human vascular function and to determine oral BH4 pharmacokinetics in both plasma and vascular tissue in patients with coronary artery disease...
  18. ncbi Tetrahydrobiopterin improves endothelium-dependent vasodilation in chronic smokers : evidence for a dysfunctional nitric oxide synthase
    T Heitzer
    Universitats Krankenhaus Eppendorf, Abteilung Kardiologie, Hamburg, Germany
    Circ Res 86:E36-41. 2000
    ..These data support the concept that in addition to the free radical burden of cigarette smoke, a dysfunctional NOS III due to BH4 depletion may contribute at least in part to endothelial dysfunction in chronic smokers...
  19. ncbi Endothelial nitric oxide synthase dysfunction in diabetic mice: importance of tetrahydrobiopterin in eNOS dimerisation
    S Cai
    Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK
    Diabetologia 48:1933-40. 2005
    ..In this regard, we investigated the role of tetrahydrobiopterin (BH4) bioavailability in regulating endothelial nitric oxide synthase (eNOS) activity, dimerisation and SO production in streptozotocin-induced diabetic mice...
  20. ncbi Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase
    Beat Thony
    Division of Clinical Chemistry and Biochemistry, University Children s Hospital, Zurich, Switzerland
    Hum Mutat 27:870-8. 2006
    ..Details on all mutations presented here are constantly updated in the BIOMDB database (www.bh4.org)...
  21. pmc Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite
    Ming Hui Zou
    Vascular Biology Unit, Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA
    J Clin Invest 109:817-26. 2002
    ..in diabetes, contributing further to endothelial cell oxidant stress. Regulation of the zinc-thiolate center of NOS by ONOO(-) provides a novel mechanism for modulation of the enzyme function in disease...
  22. pmc Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase
    Karel Chalupsky
    Section of Cardiology, Department of Medicine, Division of Biological Sciences and Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 102:9056-61. 2005
    ..This signaling cascade may represent a universal mechanism underlying eNOS dysfunction under pathophysiological conditions associated with oxidant stress...
  23. pmc Identification and functional characterization of phosphorylation sites on GTP cyclohydrolase I
    Jianhai Du
    Division of Pediatric Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Arterioscler Thromb Vasc Biol 29:2161-8. 2009
    ..Here, we identified specific phosphorylation sites on GCH-1 and characterized the function of these sites...
  24. pmc Donor pretreatment with tetrahydrobiopterin saves pancreatic isografts from ischemia reperfusion injury in a mouse model
    M Maglione
    Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Center of Operative Medicine, Innsbruck Medical University, Austria
    Am J Transplant 10:2231-40. 2010
    ..002) and improved survival and endocrine function (p = 0.0002 each). H4B donor pretreatment abrogates ischemia-induced parenchymal damage and represents a promising strategy to prevent IRI following pancreas transplantation...
  25. pmc Partial biopterin deficiency disturbs postnatal development of the dopaminergic system in the brain
    Daigo Homma
    Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226 8501, Japan
    J Biol Chem 286:1445-52. 2011
    ..We found that biopterin contents in the brains of these knock-out mice were moderately decreased from postnatal day 0 (P0) and remained ..
  26. pmc Autophagy induction by tetrahydrobiopterin deficiency
    Sang Su Kwak
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea
    Autophagy 7:1323-34. 2011
    ..In addition, this study first documents mTORC1 inactivation and autophagy induction in PKU patients with BH₄ deficiency...
  27. ncbi Quantitation of total biopterin and tetrahydrobiopterin in plasma
    Durk Fekkes
    Department of Neuroscience, Laboratory of Neurobiology, Room Ee 1438, Erasmus MC, P O Box 1738, 3000 DR Rotterdam, The Netherlands
    Clin Biochem 40:411-3. 2007
    To develop a reliable method for the determination of tetrahydrobiopterin and total biopterin in plasma.
  28. ncbi Pivotal role for endothelial tetrahydrobiopterin in pulmonary hypertension
    Jeffrey P Khoo
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
    Circulation 111:2126-33. 2005
    ..Recent evidence suggests that the cofactor tetrahydrobiopterin (BH4) is an important regulator of nitric oxide synthase enzymatic function...
  29. ncbi Beneficial effect of tetrahydrobiopterin on ischemia-reperfusion injury in isolated perfused rat hearts
    Satoshi Yamashiro
    Department of Pharmacology, School of Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903 0215, Japan
    J Thorac Cardiovasc Surg 124:775-84. 2002
    ..The aim of this study was to clarify whether supplement with tetrahydrobiopterin would exert a cardioprotective effect against ischemia-reperfusion injury...
  30. pmc GTP cyclohydrolase I phosphorylation and interaction with GTP cyclohydrolase feedback regulatory protein provide novel regulation of endothelial tetrahydrobiopterin and nitric oxide
    Li Li
    Division of Cardiology, Emory University School of Medicine, 1639 Pierce Dr WMBR 319, Atlanta, GA 30322, USA
    Circ Res 106:328-36. 2010
    ....
  31. ncbi Mechanisms underlying responsiveness to tetrahydrobiopterin in mild phenylketonuria mutations
    Angel L Pey
    Centro de Biologia Molecular Severo Ochoa, CSIC Universidad Autonoma de Madrid, Madrid, Spain
    Hum Mutat 24:388-99. 2004
    ..Both effects of BH4 on PAH, i.e., the chemical chaperone effect preventing protein misfolding and the protection from inactivation, may be relevant mechanisms of the responsive phenotype...
  32. ncbi Role of tetrahydrobiopterin in adrenocorticotropic hormone-induced hypertension in the rat
    Y Zhang
    High Blood Pressure Research Unit, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia
    Clin Exp Hypertens 26:231-41. 2004
    ..There was no significant difference in SBP between BH4 + ACTH treated and vehicle + ACTH treated rats. Thus, daily injection of BH4 (10 mg/kg i.p.) failed to prevent the development of ACTH-induced hypertension in rat...
  33. ncbi Altered plasma versus vascular biopterins in human atherosclerosis reveal relationships between endothelial nitric oxide synthase coupling, endothelial function, and inflammation
    Charalambos Antoniades
    Department of Cardiovascular Medicine, University of Oxford, Oxford, UK
    Circulation 116:2851-9. 2007
    ..We sought to define the relationships between plasma and vascular biopterin levels in patients with coronary artery disease and to determine how BH4 levels affect endothelial function, ..
  34. pmc Thiol-metabolizing proteins and endothelial redox state: differential modulation of eNOS and biopterin pathways
    Toru Sugiyama
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Physiol Heart Circ Physiol 298:H194-201. 2010
    ..Greater understanding of the differential regulation of thiol-metabolizing proteins may lead to the development of new pharmacological targets for diseases associated with oxidative stress in the vascular wall...
  35. pmc Catalytic residues and a predicted structure of tetrahydrobiopterin-dependent alkylglycerol mono-oxygenase
    Katrin Watschinger
    Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz Pregl Strasse 3 VI, A 6020 Innsbruck, Austria
    Biochem J 443:279-86. 2012
    ..Prediction of a part of the structure using the Rosetta membrane ab initio method led to a plausible suggestion for a structure of the catalytic site of alkylglycerol mono-oxygenase...
  36. pmc A murine model for human sepiapterin-reductase deficiency
    Seungkyoung Yang
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea
    Am J Hum Genet 78:575-87. 2006
    ..This Spr mutant strain of mice will be an invaluable resource to elucidate many important issues regarding SPR and BH(4) deficiencies...
  37. ncbi Endogenous methylarginines modulate superoxide as well as nitric oxide generation from neuronal nitric-oxide synthase: differences in the effects of monomethyl- and dimethylarginines in the presence and absence of tetrahydrobiopterin
    Arturo J Cardounel
    Davis Heart and Lung Research Institute and the Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA
    J Biol Chem 280:7540-9. 2005
    ..generation from nNOS. These observations have important implications with regard to the therapeutic use of methylarginine-NOS inhibitors in the treatment of disease...
  38. doi Metabolism of tetrahydrobiopterin: its relevance in monoaminergic neurons and neurological disorders
    Hiroshi Ichinose
    Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226 8501, Japan
    Chem Rec 8:378-85. 2008
    ..Our research suggests that BH4 metabolism in the brain should be different from that in the liver, and that altered metabolism of BH4 should lead to neuropsychiatric disorders including Parkinson's disease...
  39. ncbi Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both normotensive and hypertensive individuals
    Yukihito Higashi
    First Department of Internal Medicine, Hiroshima University, Faculty of Medicine, Japan
    Am J Hypertens 15:326-32. 2002
    ..The purpose of this study was to determine whether BH4 restores endothelium-dependent vasodilation in patients with essential hypertension...
  40. ncbi Purification and cloning of the GTP cyclohydrolase I feedback regulatory protein, GFRP
    S Milstien
    Laboratory of Cell Biology, National Institute of Mental Health
    J Biol Chem 271:19743-51. 1996
    ..These results suggest that GFRP is widely expressed and may play a role in regulating not only phenylalanine metabolism in the liver, but also the production of biogenic amine neurotransmitters as well as nitric oxide synthesis...
  41. ncbi Reaction of tetrahydrobiopterin with superoxide: EPR-kinetic analysis and characterization of the pteridine radical
    J Vasquez-Vivar
    Department of Pathology, Medical College of Wisconsin, Milwaukee, 53226, USA
    Free Radic Biol Med 31:975-85. 2001
    ..In conclusion, it is likely that BH(4)-dependent inhibition of superoxide formation from eNOS is the mechanism that better explains the antioxidant effects of BH(4) in the vasculature...
  42. doi Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies
    Nenad Blau
    University Children s Hospital, Zurich, Switzerland
    Mol Genet Metab 104:S2-9. 2011
    ..best sample for the simultaneous measurement of amino acids (phenylalanine and tyrosine), pterins (neopterin and biopterin), and dihydropteridine reductase activity from a single specimen...
  43. pmc Modeling of biopterin-dependent pathways of eNOS for nitric oxide and superoxide production
    Saptarshi Kar
    Department of Biomedical Engineering, Wayne State University, Detroit, MI 48202, USA
    Free Radic Biol Med 51:1411-27. 2011
    ..The importance of the ratio of BH(4) to oxidized biopterins versus absolute levels of total biopterin in determining the extent of eNOS uncoupling remains to be determined...
  44. pmc Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency
    Mark J Crabtree
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
    Free Radic Biol Med 50:1639-46. 2011
    ..Taken together, these data reveal a key role for DHFR in regulating the BH4 vs BH2 ratio and eNOS coupling under conditions of low total biopterin availability in vivo.
  45. pmc GTP cyclohydrolase I expression, protein, and activity determine intracellular tetrahydrobiopterin levels, independent of GTP cyclohydrolase feedback regulatory protein expression
    Amy L Tatham
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom
    J Biol Chem 284:13660-8. 2009
    ..We suggest that GTPCH expression is the primary regulator of BH4 levels, and changes in GTPCH or BH4 are not necessarily accompanied by changes in GFRP expression...
  46. pmc Deficient BH4 production via de novo and salvage pathways regulates NO responses to cytokines in adult cardiac myocytes
    Irina A Ionova
    Department of Surgery Transplant Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Am J Physiol Heart Circ Physiol 295:H2178-87. 2008
    ....
  47. pmc Tetrahydrobiopterin recycling, a key determinant of endothelial nitric-oxide synthase-dependent signaling pathways in cultured vascular endothelial cells
    Toru Sugiyama
    Cardiovascular and Pulmonary Divisions, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Biol Chem 284:12691-700. 2009
    ..an enzyme-recycling oxidized BH4 (7,8-dihydrobiopterin (BH2)), and studied the effects on eNOS regulation and biopterin metabolism in cultured aortic endothelial cells...
  48. pmc Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrobiopterin dependence
    Katrin Watschinger
    Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Fritz Pregl Str 3 VI, A 6020 Innsbruck, Austria
    Biol Chem 390:3-10. 2009
    ....
  49. doi Tetrahydrobiopterin: a novel antihypertensive therapy
    M Porkert
    Division of Cardiology, Emory University, Atlanta, GA, USA
    J Hum Hypertens 22:401-7. 2008
    ....
  50. pmc Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations
    Heidi Erlandsen
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:16903-8. 2004
    ..Of fundamental importance is the observation that BH4 appears to increase Phe catabolism if at least one of the two heterozygous mutations has any residual activity remaining...
  51. pmc Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability
    Søren W Gersting
    Department of Molecular Pediatrics, Children s Research Center, Dr von Hauner Children s Hospital, Ludwig Maximilians University, 80337 Munich, Germany
    Am J Hum Genet 83:5-17. 2008
    ..Thus, PKU has evolved from a model of a genetic disease that leads to severe neurological impairment to a model of a treatable protein-folding disease with loss of function...
  52. ncbi GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence
    Irmgard Tegeder
    Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 4309, Charlestown, Massachusetts 02129, USA
    Nat Med 12:1269-77. 2006
    ..BH4 is therefore an intrinsic regulator of pain sensitivity and chronicity, and the GTP cyclohydrolase haplotype is a marker for these traits...
  53. ncbi Crystal structure of the ternary complex of the catalytic domain of human phenylalanine hydroxylase with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine, and its implications for the mechanism of catalysis and substrate activation
    Ole Andreas Andersen
    Department of Chemistry, University of Tromsø, N 9037, Tromso, Norway
    J Mol Biol 320:1095-108. 2002
    ..The large conformational change, moving Tyr138 from a surface position into the active site, may reflect a possible functional role for this residue...
  54. ncbi Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin
    J B Laursen
    Department of Medicine, Emory University School of Medicine, and Veterans Administration Hospital, Atlanta, GA 30322, USA
    Circulation 103:1282-8. 2001
    ..Peroxynitrite oxidation of tetrahydrobiopterin may represent a pathogenic cause of "uncoupling" of NO synthase...
  55. pmc Ascorbic acid and tetrahydrobiopterin potentiate the EDHF phenomenon by generating hydrogen peroxide
    Ambroise Garry
    Department of Diagnostic Radiology, Wales Heart Research Institute, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    Cardiovasc Res 84:218-26. 2009
    ..Our objective was to investigate whether pro-oxidant properties of ascorbic acid (AA) and tetrahydrobiopterin (BH(4)) modulate endothelium-dependent, electrotonically mediated arterial relaxation...
  56. pmc Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction
    GAD A SILBERMAN
    Department of Medicine Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA
    Circulation 121:519-28. 2010
    ..Similar events may occur in the heart that lead to uncoupled NOS and diastolic dysfunction...
  57. ncbi 2.0A resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine or L-norleucine: substrate specificity and molecular motions related to substrate binding
    Ole Andreas Andersen
    Department of Chemistry, Faculty of Science, University of Tromsø, N 9037, Tromsø, Norway
    J Mol Biol 333:747-57. 2003
    ..However, the specific activity with NLE as the substrate was only about 5% of that with THA, which is explained by the different affinities of binding and different catalytic turnover...
  58. ncbi NAD(P)H oxidase and uncoupled nitric oxide synthase are major sources of glomerular superoxide in rats with experimental diabetic nephropathy
    Minoru Satoh
    Div of Nephrology, Dept of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701 0192, Japan
    Am J Physiol Renal Physiol 288:F1144-52. 2005
    ..Our results indicate that NAD(P)H oxidase and uncoupling of eNOS contribute to glomerular ROS production, mediated by the loss of BH4 availability. These mechanisms are potential key targets for therapeutic interventions...
  59. doi IGF-I alleviates diabetes-induced RhoA activation, eNOS uncoupling, and myocardial dysfunction
    Jun Ren
    School of Pharmacy, University of Wyoming, Laramie, WY 82071, USA
    Am J Physiol Regul Integr Comp Physiol 294:R793-802. 2008
    ..These results revealed that IGF-I benefits diabetic hearts via Rho inhibition and antagonism of diabetes-induced decrease in pAkt, eNOS uncoupling, and K+ channel expression...
  60. ncbi Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in fibroblasts
    L Bonafe
    Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
    Clin Chem 47:477-85. 2001
    ..The aim of the study was to determine the utility of cultured skin fibroblasts for the diagnosis of these diseases...
  61. doi Disorders of biopterin metabolism
    Nicola Longo
    Division of Medical Genetics, Department of Pediatrics and Pathology, University of Utah, 2C 412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132, USA
    J Inherit Metab Dis 32:333-42. 2009
    ..the exception of sepiapterin reductase and the dominant form of GTP cyclohydrolase I deficiency that results in biopterin deficiency/insufficiency only in the brain...
  62. ncbi Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase
    H Erlandsen
    Departments of Molecular Biology and Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 39:2208-17. 2000
    ..residues 118-424) of human PheOH (hPheOH), cocrystallized with the oxidized form of the cofactor (7,8-dihydro-L-biopterin, BH(2)), has been determined at 2.0 A resolution...
  63. ncbi Molecular characterization of HPH-1: a mouse mutant deficient in GTP cyclohydrolase I activity
    M Gutlich
    GSF Institut für Klinische Molekularbiologie, Munchen, Germany
    Biochem Biophys Res Commun 203:1675-81. 1994
    ..The open reading frame of GTP cyclohydrolase I is not affected by the hph-1 mutation as shown by sequencing. Northern blot analysis demonstrates a marked decrease in the steady state mRNA level specific for GTP cyclohydrolase I...
  64. ncbi A tetrahydrobiopterin radical forms and then becomes reduced during Nomega-hydroxyarginine oxidation by nitric-oxide synthase
    Chin Chuan Wei
    Department of Immunology, The Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Biol Chem 278:46668-73. 2003
    ..We used stopped-flow spectroscopy and rapid-freeze EPR spectroscopy to follow heme and biopterin transformations during single-turnover NOHA oxidation reactions catalyzed by the oxygenase domain of inducible ..
  65. pmc Tetrahydrobiopterin as a novel therapeutic intervention for autism
    Richard E Frye
    Division of Child and Adolescent Neurology and The Children s Learning Institute, Department of Pediatrics, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA
    Neurotherapeutics 7:241-9. 2010
    ....
  66. ncbi Molecular mechanism for pterin-mediated inactivation of tyrosine hydroxylase: formation of insoluble aggregates of tyrosine hydroxylase
    Fumi Urano
    Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226 8501
    J Biochem 139:625-35. 2006
    ..enzyme at a concentration far less than the Km value toward BH4 in spite of its cofactor role, whereas oxidized biopterin, which has no cofactor activity, does not affect the enzyme activity...
  67. doi Endothelial, sympathetic, and cardiac function in inherited (6R)-L-erythro-5,6,7,8-tetrahydro-L-biopterin deficiency
    Lila Mayahi
    Centre for Clinical Pharmacology, University College London, 5 University St, London, UK
    Circ Cardiovasc Genet 3:513-22. 2010
    6R)-5,6,7,8-Tetrahydro-l-biopterin (BH4) is a cofactor for enzymes involved in catecholamine and nitric oxide generation whose synthesis is initiated by GTP cyclohydrolase I (GTPCH-1), encoded by GCH1...
  68. ncbi Physarum polycephalum expresses a dihydropteridine reductase with selectivity for pterin substrates with a 6-(1', 2'-dihydroxypropyl) substitution
    Claudia Wild
    Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz Pregl Str 3, A 6020 Innsbruck, Austria
    Biol Chem 384:1057-62. 2003
    ..Our results demonstrate that Physarum synthesizes, utilizes and metabolizes tetrahydrobiopterin in a way hitherto thought to be restricted to the animal kingdom...
  69. ncbi Congenic mapping and genotyping of the tetrahydrobiopterin-deficient hph-1 mouse
    Jeffrey P Khoo
    Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
    Mol Genet Metab 82:251-4. 2004
    ..These new findings will extend the utility of the hph-1 mouse in studies of GTP-CH I deficiency...
  70. ncbi Formation of a protonated trihydrobiopterin radical cation in the first reaction cycle of neuronal and endothelial nitric oxide synthase detected by electron paramagnetic resonance spectroscopy
    P P Schmidt
    Department of Biochemistry, University of Oslo, Norway
    J Biol Inorg Chem 6:151-8. 2001
    ..These results offer strong support for redox cycling of BH4 in the first reaction cycle of NOS catalysis (BH4 <--> BH3.H+)...
  71. ncbi Determination of quinonoid dihydrobiopterin by high-performance liquid chromatography and electrochemical detection
    S Heales
    Department of Child Health, Institute of Child Health, London, U K
    J Chromatogr 494:77-85. 1989
    ..This method is shown to be quantitative and preliminary experiments demonstrate that it can be adapted for biological samples...
  72. pmc High affinity S-Adenosylmethionine plasma membrane transporter of Leishmania is a member of the folate biopterin transporter (FBT) family
    Larbi Dridi
    Centre de Recherche en Infectiologie du CHUL, Universite Laval, Quebec City, Quebec G1V 4G2, Canada
    J Biol Chem 285:19767-75. 2010
    ..Leishmania cells resistant to the antifolate methotrexate due to a rearrangement in folate biopterin transporter (FBT) genes were cross-resistant to sinefungin, an AdoMet analogue...
  73. pmc Suppression of eNOS-derived superoxide by caveolin-1: a biopterin-dependent mechanism
    Kanchana Karuppiah
    Department of Anesthesiology, Ohio State University, Columbus, Ohio, USA
    Am J Physiol Heart Circ Physiol 301:H903-11. 2011
    ....
  74. pmc Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS
    Mark J Crabtree
    Dept of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Am J Physiol Heart Circ Physiol 294:H1530-40. 2008
    ..Whereas the total biopterin pool of murine endothelial cells (ECs) was unaffected by 48-h exposure to diabetic glucose levels (30 mM), BH(2) ..
  75. ncbi Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase
    Tomasz J Guzik
    Department of Cardiovascular Medicine, University of Oxford, Oxford, UK
    Circulation 105:1656-62. 2002
    ..We characterized the sources and mechanisms underlying vascular superoxide production in human blood vessels from diabetic patients with coronary artery disease compared with nondiabetic patients...
  76. ncbi L-Ascorbic acid potentiates nitric oxide synthesis in endothelial cells
    R Heller
    Center of Vascular Biology and Medicine, Friedrich Schiller University of Jena, 99089 Erfurt, Germany
    J Biol Chem 274:8254-60. 1999
    ..Our data suggest that intracellular ascorbic acid enhances NO synthesis in endothelial cells and that this may explain, in part, the beneficial vascular effects of ascorbic acid...
  77. ncbi Gene transfer of human guanosine 5'-triphosphate cyclohydrolase I restores vascular tetrahydrobiopterin level and endothelial function in low renin hypertension
    Jie sheng Zheng
    Department of Pharmacology and Toxicology and the Neuroscience Program, B403 Life Sciences Building, Michigan State University, East Lansing, Mich 48824 1317, USA
    Circulation 108:1238-45. 2003
    ..However, the interaction between O2- and BH4 on endothelial function and the underlying mechanisms are unknown...
  78. ncbi Esrom, an ortholog of PAM (protein associated with c-myc), regulates pteridine synthesis in the zebrafish
    Sylvie Le Guyader
    Developmental Neurobiology Group, Temasek Life Sciences Laboratory, Singapore 117604, Singapore
    Dev Biol 277:378-86. 2005
    ..They also raise the possibility that neuronal defects are due in part to an abnormality in pteridine synthesis...
  79. pmc Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency
    C J Meininger
    Cardiovascular Research Institute and Department of Medical Physiology, The Texas A and M University System Health Science Center, College Station, TX 77843 1114, USA
    Biochem J 349:353-6. 2000
    ..GTP-cyclohydrolase activity was low because of a decreased expression of the protein in the diabetic cells...
  80. ncbi HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells
    Yoshiyuki Hattori
    Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi 321 0293, Japan
    Arterioscler Thromb Vasc Biol 23:176-82. 2003
    ..We investigated the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, in terms of BH4 metabolism in human umbilical vein endothelial cells (HUVECs)...
  81. ncbi Effect of light therapy on biopterin, neopterin and tryptophan in patients with seasonal affective disorder
    Rocco Hoekstra
    DeltaBouman Psychiatric Teaching Hospital, Postbus 800, Poortugaal 3170 DZ, The Netherlands
    Psychiatry Res 120:37-42. 2003
    ..The present study was designed to measure levels of biopterin, neopterin and tryptophan in plasma of 19 depressed patients with a history of SAD, before and after light ..
  82. ncbi The effect of high glucose on NO and O2- through endothelial GTPCH1 and NADPH oxidase
    Qun Fang Ding
    Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma cho, Shawa ku, Nagoya, 466 8550, Japan Department of Geriatrics, The First University Hospital of West China University of Medical Sciences, Chengdu, China
    Life Sci 75:3185-94. 2004
    ..Conclusively, high glucose leads to eNOS dysfunction by inhibiting BH4 synthesis and atorvastatin stimulate BH4 synthesis directly, and it may work as atherogenic process...
  83. ncbi Structure of nitric oxide synthase oxygenase dimer with pterin and substrate
    B R Crane
    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 279:2121-6. 1998
    ..L-Arginine binds to glutamic acid-371 and stacks with heme in an otherwise hydrophobic pocket to aid activation of heme-bound oxygen by direct proton donation and thereby differentiate the two chemical steps of nitric oxide synthesis...
  84. pmc Inducible nitric oxide synthase: role of the N-terminal beta-hairpin hook and pterin-binding segment in dimerization and tetrahydrobiopterin interaction
    D K Ghosh
    Department of Immunology, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH 44195, USA
    EMBO J 18:6260-70. 1999
    ..This suggests a mechanism whereby N-terminal hooks exchange between subunits in solution to stabilize the dimer...
  85. ncbi Tetrahydrobiopterin radical enzymology
    Chin Chuan Wei
    Department of Immunology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Chem Rev 103:2365-83. 2003
  86. ncbi The two faces of endothelial nitric oxide synthase in the pathophysiology of atherosclerosis
    Seinosuke Kawashima
    Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
    Endothelium 11:99-107. 2004
    ..This review focuses on two faces of eNOS as both an NO- as well as superoxide-producing enzyme depending on tissue pteridine metabolisms in the pathophysiology of atherosclerosis...
  87. ncbi Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects
    Nikolaj Ihlemann
    Department of Cardiology, Bldg 40, Bispebjerg University Hospital, Bispebjerg Bakke 23, DK 2400 Copenhagen, Denmark
    Am J Physiol Heart Circ Physiol 285:H875-82. 2003
    ..On different days (6R)-5,6,7,8-tetrahydro-l-biopterin dihydrochloride (6R-BH4; n = 10), the active cofactor of eNOS or its stereoisomer (6S)-5,6,7,8-tetrahydro-l-..
  88. ncbi Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center
    C S Raman
    Department of Molecular Biology and Biochemistry, University of California, Irvine 92697 3900, USA
    Cell 95:939-50. 1998
    ..The unexpected recognition of the substrate, L-arginine, at the H4B site indicates that this site is poised to stabilize a positively charged pterin ring and suggests a model involving a cationic pterin radical in the catalytic cycle...
  89. ncbi The pteridine pathway in zebrafish: regulation and specification during the determination of neural crest cell-fate
    Irmgard Ziegler
    GSF Institut für Klinische Molekularbiologie und Tumorgenetik, Munchen, Germany
    Pigment Cell Res 16:172-82. 2003
    ....
  90. ncbi Nitric oxide dynamics and endothelial dysfunction in type II model of genetic diabetes
    Milad S Bitar
    Department of Pharmacology, Kuwait University, School of Medicine, Kuwait
    Eur J Pharmacol 511:53-64. 2005
    ..This phenomenon could play a potentially important role in the pathogenesis of diabetic endothelial dysfunction...
  91. ncbi Effect of electroconvulsive therapy on biopterin and large neutral amino acids in severe, medication-resistant depression
    R Hoekstra
    Department of Psychiatry, University Hospital Rotterdam Dijkzigt, Rotterdam, The Netherlands
    Psychiatry Res 103:115-23. 2001
    b>Biopterin, neopterin and the large neutral amino acids (LNAA), i.e...
  92. ncbi GTP cyclohydrolase feedback regulatory protein controls cofactor 6-tetrahydrobiopterin synthesis in the cytosol and in the nucleus of epidermal keratinocytes and melanocytes
    Bhaven Chavan
    Clinical and Experimental Dermatology Department of Biomedical Sciences University of Bradford, Bradford, UK
    J Invest Dermatol 126:2481-9. 2006
    ..Moreover, GFRP expression and GTPCHI activities have been found in the nucleus of both cell types. The significance of this result warrants further investigation...
  93. ncbi Decrease in tetrahydrobiopterin as a possible cause of nephropathy in type II diabetic rats
    M Okumura
    Department of Internal Medicine, Osaka City General Hospital, Osaka, Japan
    Kidney Int 70:471-6. 2006
    ..In type II diabetic rats, renal BH4 is considered to play a crucial role in the pathogenesis of diabetic nephropathy. Benidipine was found to preserve BH4 levels, suggesting therapeutic renoprotective effects...
  94. pmc Vascular protection by tetrahydrobiopterin: progress and therapeutic prospects
    Zvonimir S Katusic
    Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Trends Pharmacol Sci 30:48-54. 2009
    ..This review also addresses the emerging roles of BH4 in the regulation of endothelial function and their therapeutic implications...
  95. ncbi A specific role for eNOS-derived reactive oxygen species in atherosclerosis progression
    Tomofumi Takaya
    Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
    Arterioscler Thromb Vasc Biol 27:1632-7. 2007
    ..In this study, we addressed the specific importance of uncoupled eNOS in atherosclerosis, and the potential mechanistic role for specific versus nonspecific antioxidant strategies in restoring eNOS coupling...
  96. ncbi Tetrahydrobiopterin as combined electron/proton donor in nitric oxide biosynthesis: cryogenic UV-Vis and EPR detection of reaction intermediates
    Antonius C F Gorren
    Department of Pharmacology and Toxicology, Karl Franzens University Graz, Austria
    Methods Enzymol 396:456-66. 2005
    ..In this chapter, the suitability, drawbacks, and advantages of cryogenic methods are discussed...
  97. pmc Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults
    Iratxe Eskurza
    Department of Integrative Physiology, University of Colorado at Boulder, UCB 354, Boulder, CO 80309, USA
    J Physiol 568:1057-65. 2005
    ..These results suggest that BH4 bioactivity may be a key mechanism involved in the impairment of conduit artery EDD with sedentary ageing, and the EDD-preserving effect of habitual exercise...
  98. ncbi (6R)-5,6,7,8-tetrahydro-L-biopterin and its stereoisomer prevent ischemia reperfusion injury in human forearm
    Lila Mayahi
    Centre for Clinical Pharmacology, BHF Laboratories, Department of Medicine, UCL, 5 University Street, London, UK, WC1E 6JJ
    Arterioscler Thromb Vasc Biol 27:1334-9. 2007
    6R-5,6,7,8-tetrahydro-L-biopterin (6R-BH4) is a cofactor for endothelial nitric oxide synthase but also has antioxidant properties...
  99. pmc 5-Methyltetrahydrofolate and tetrahydrobiopterin can modulate electrotonically mediated endothelium-dependent vascular relaxation
    Tudor M Griffith
    Department of Diagnostic Radiology, Wales Heart Research Institute, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom
    Proc Natl Acad Sci U S A 102:7008-13. 2005
    ....
  100. ncbi Neopterin, biopterin, and nitric oxide concentrations in the cerebrospinal fluid of children with central nervous system infections
    Kohji Azumagawa
    Division of Pediatrics, Yao Tokusyu kai General Hospital, 3 15 38 Kyuhoji, Yao shi, Osaka 581 0072, Japan
    Brain Dev 25:200-2. 2003
    We measured neopterin, biopterin and nitric oxide (NO) concentrations in the cerebrospinal fluid of pediatric patients with central nervous system (CNS) infectious diseases...
  101. ncbi Adaptation of Leishmania cells to in vitro culture results in a more efficient reduction and transport of biopterin
    G Roy
    Centre de Recherche en Infectiologie du Centre de Recherche du CHUL, , , Canada
    Exp Parasitol 97:161-8. 2001
    ..donovani cells freshly isolated from infected animals divided slowly as axenic promastigotes but the addition of biopterin in the culture medium greatly enhanced their growth...

Research Grants75

  1. DRUG RESISTANCE AND PTERIDINE METABOLISM IN LEISHMANIA
    Stephen M Beverley; Fiscal Year: 2010
    ..Leishmania parasites, which has lead us into studies of the metabolism of the unconjugated pteridine biopterin and the conjugated pteridine folate, and the development and application of new genetic tools...
  2. DRUG RESISTANCE AND PTERIDINE METABOLISM IN LEISHMANIA
    Stephen Beverley; Fiscal Year: 2009
    ..Leishmania parasites, which has lead us into studies of the metabolism of the unconjugated pteridine biopterin and the conjugated pteridine folate, and the development and application of new genetic tools...
  3. DRUG RESISTANCE AND GENE AMPLIFICATION IN LEISHMANIA
    Stephen Beverley; Fiscal Year: 2007
    ..Our previous studies revealed for the first time a role for biopterin specifically in parasite differentiation to the infective metacyclic stage, and possibly other pathways relevant ..
  4. DRUG RESISTANCE AND GENE AMPLIFICATION IN LEISHMANIA
    Stephen Beverley; Fiscal Year: 2006
    ..Our previous studies revealed for the first time a role for biopterin specifically in parasite differentiation to the infective metacyclic stage, and possibly other pathways relevant ..
  5. Hsp90, NOS3 and Cardioprotection
    Yang Shi; Fiscal Year: 2007
    ..with NOS3 in BN/Mcw hearts was increased nearly 2-fold compared to association in SS/Mcw hearts; and that total biopterin, an analytical index of tetrahydrobiopterin (BH4) was increased in BN/Mcw hearts by 80%...
  6. Hsp90, NOS3 and Cardioprotection
    Yang Shi; Fiscal Year: 2009
    ..NOS3 in BN/Mcw hearts was increased nearly 2-fold compared to association in SS/Mcw hearts; and that total biopterin, an analytical index of tetrahydrobiopterin (BH4) was increased in BN/Mcw hearts by 80%...
  7. BIOPTERIN, CATECHOLAMINES, & NO IN REGULATING APOPTOSIS
    Robert Levine; Fiscal Year: 2002
    ..These studies may will reveal novel apoptotic regulatory mechanisms and provide new avenues for therapeutic approaches to promote neuronal survival and prevent debilitating neurological diseases, such as Parkinson's disease. ..
  8. EPR Studies of Biological PCET Elements
    R Britt; Fiscal Year: 2007
    ..A biopterin radical is transiently formed in the conversion of arginine to NHA, and a similar radical intermediate likely ..
  9. Biopterin Deficit in Schizophrenia: Genetic Dissection of BH4 Biosynthesis.
    JAMES CLELLAND; Fiscal Year: 2007
    ..Based on the central roles of BH4 in NT synthesis, we assayed plasma total biopterin levels (a measure of BH4) in a large sample of patients with SZ and control subjects...
  10. CIRCULATORY SHOCK, NITRIC OXIDE AND TETRAHYDROBIOPTERIN
    Steven Gross; Fiscal Year: 2003
    ..These studies will improve our understanding of BH4 regulation and function and may provide insights that lead to novel biopterin-based strategies for pharmacotherapy of septic shock and other conditions arising from NO excess.
  11. Redox properties of heme-oxygenase in NO synthases
    Mekki Bayachou; Fiscal Year: 2003
    ..the amino acid L-arginine by a class of enzymes known as Nitric Oxide Synthases (NOSs) requiring a P450-heme, a biopterin cofactor and molecular oxygen in its oxygenase domain...
  12. Oxidative Stress and Pteridine Metabolism in Diabetes
    Cynthia Meininger; Fiscal Year: 2005
    ..rat [as a model of type I! diabetes], we will measure the cellular content of GTPCH, BH4, dihydrobiopterin (plus biopterin), and eNOS, as well as GTPCH activity and NO synthesis at different time points during disease progression and ..
  13. Air Pollution Exposure/Atherosclerosis:Vascular Mechanism
    Sanjay Rajagopalan; Fiscal Year: 2007
    ..cofactor vascular 6R-5,6,7,8-tetrahydrobiopterin (BH4) and its oxidized analogs [7,8 dihydrobiopterin (BH2) and biopterin] in arterial segments derived from Apo E-/- exposed to CAPS...
  14. Structure-Function and Reacation Mechanism of eNOS
    Ah Lim Tsai; Fiscal Year: 2007
    ..a NO synthase rather than a superoxide synthase activity, we will obtain complete kinetic data of different biopterin redox species including its radical intermediate during single and multiple turnover reaction of eNOS...
  15. Superoxide Generation from eNOS: The Role of Pterins
    JEANNETTE M VASQUEZ VIVAR; Fiscal Year: 2010
    ..Generally this proposal is aimed at understanding these fundamental mechanisms that should provide the basis for developing new and improved strategies in the prevention and treatment of atherosclerosis and CVD. ..
  16. Superoxide Generation from eNOS: The Role of Pterins
    Jeannette Vasquez Vivar; Fiscal Year: 2009
    ..Generally this proposal is aimed at understanding these fundamental mechanisms that should provide the basis for developing new and improved strategies in the prevention and treatment of atherosclerosis and CVD. ..
  17. Superoxide Generation from eNOS: The Role of Pterins
    Jeannette Vasquez Vivar; Fiscal Year: 2007
    ..Generally this proposal is aimed at understanding these fundamental mechanisms that should provide the basis for developing new and improved strategies in the prevention and treatment of atherosclerosis and CVD. ..
  18. Superoxide Generation from eNOS: The Role of Pterins
    Jeannette Vasquez Vivar; Fiscal Year: 2006
    ..abstract_text> ..
  19. Superoxide Generation from eNOS: The Role of Pterins
    Jeannette Vasquez Vivar; Fiscal Year: 2003
    ..abstract_text> ..
  20. Tetrahydrobiopterin in Hypoxia-Ischemia Induced Fetal Brain Dysfunction
    Jeannette Vasquez Vivar; Fiscal Year: 2007
    ..This information will likely define the use of tetrahydrobiopterin in the prevention and/or amelioration of H-I induced fetal brain dysfunction, which remains a major medical challenge. ..
  21. iNOS Posttranslational Regulation in Cardiac Rejection
    GALEN PIEPER; Fiscal Year: 2009
    ..A better understanding of this molecular process may lead to better strategies to prevent injury cardiac cells in these patients. ..
  22. MOLECULAR TARGETS OF NITRIC OXIDE IN CARDIAC TRANSPLANTS
    GALEN PIEPER; Fiscal Year: 2004
    ..These studies will provide a novel mechanism to explain the pathogenesis of dyskinesis and graft failure during cardiac transplant rejection. ..
  23. IGF-1, Oxidative Stress and Cardiovascular Aging
    Jun Ren; Fiscal Year: 2002
    ..Our long-term goal is to establish the causal link among IGF-1 deficiency, enhanced oxidative damage and ventricular dysfunction in the progression of cardiovascular aging so that hormonal or antioxidant therapy can be optimized...