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 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
  4. ncbi 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
  5. 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
  6. 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
  7. 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
  8. ncbi Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease
    Mark J Crabtree
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
    Nitric Oxide 25:81-8. 2011
  9. ncbi 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling
    Charalambos Antoniades
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK
    Circulation 114:1193-201. 2006
  10. 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

Detail Information

Publications284 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 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
    ....
  4. ncbi 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...
  5. 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...
  6. 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...
  7. 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...
  8. ncbi Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease
    Mark J Crabtree
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
    Nitric Oxide 25:81-8. 2011
    ..These studies indicate that not only BH4 level, but the recycling pathways regulating BH4 bioavailability represent potential therapeutic targets and will be discussed in this review...
  9. ncbi 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling
    Charalambos Antoniades
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK
    Circulation 114:1193-201. 2006
    ..We hypothesized that 5-MTHF would improve endothelial function by decreasing superoxide and peroxynitrite production and by improving eNOS coupling, mediated by BH4 availability...
  10. 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
    ....
  11. pmc eNOS uncoupling and endothelial dysfunction in aged vessels
    Yang Ming Yang
    Department of Physiology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Heart Circ Physiol 297:H1829-36. 2009
    ....
  12. 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...
  13. 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...
  14. ncbi L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin
    R Heller
    Center of Vascular Biology and Medicine, Friedrich Schiller University of Jena, D 99089 Erfurt, Germany
    J Biol Chem 276:40-7. 2001
    ..endothelial cells coincubated with cytokines and ascorbate was associated with a decrease of more oxidized biopterin derivatives (7,8-dihydrobiopterin and biopterin) in cells and cell supernatants...
  15. 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...
  16. pmc Role of neural NO synthase (nNOS) uncoupling in the dysfunctional nitrergic vasorelaxation of penile arteries from insulin-resistant obese Zucker rats
    Ana Sanchez
    Departamento de Fisiologia, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain
    PLoS ONE 7:e36027. 2012
    ..The present study assessed the role of oxidative stress in the dysfunctional neural vasodilator responses of penile arteries in the obese Zucker rat (OZR), an experimental model of metabolic syndrome/prediabetes...
  17. 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...
  18. 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...
  19. 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...
  20. 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 ..
  21. 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...
  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. ncbi 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...
  24. 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...
  25. ncbi Tetrahydrobiopterin, but not L-arginine, decreases NO synthase uncoupling in cells expressing high levels of endothelial NO synthase
    Lonneke M Bevers
    Department of Nephrology and Hypertension, Institute and Graduate School of Biomembranes, University Medical Centre, Utrecht, The Netherlands
    Hypertension 47:87-94. 2006
    Endothelial NO synthase (eNOS) produces superoxide when depleted of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) and L-arginine by uncoupling the electron flow from NO production...
  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. 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...
  28. ncbi 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...
  29. ncbi Sepiapterin enhances angiogenesis and functional recovery in mice after myocardial infarction
    Takayuki Shimazu
    Second Department of Internal Medicine, Kansai Medical University, Moriguchi City, Japan
    Am J Physiol Heart Circ Physiol 301:H2061-72. 2011
    ..These results suggest that sepiapterin enhances angiogenesis and functional recovery after MI by activating the salvage pathway for BH(4) synthesis and increasing bioavailable nitric oxide predominantly derived from iNOS...
  30. ncbi Tetrahydrobiopterin protects soluble guanylate cyclase against oxidative inactivation
    Kurt Schmidt
    Department of Pharmacology and Toxicology, Karl Franzens Universitat Graz, Graz, Austria
    Mol Pharmacol 82:420-7. 2012
    ..Protection of sGC against oxidative inactivation may contribute to the known beneficial effects of BH4 in cardiovascular disorders associated with oxidative stress...
  31. pmc Integrated redox sensor and effector functions for tetrahydrobiopterin- and glutathionylation-dependent endothelial nitric-oxide synthase uncoupling
    Mark J Crabtree
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
    J Biol Chem 288:561-9. 2013
    ....
  32. 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...
  33. ncbi Tetrahydrobiopterin availability in Parkinson's and Alzheimer's disease; potential pathogenic mechanisms
    Richard H Foxton
    Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, WC1N 3BG, UK
    Neurochem Res 32:751-6. 2007
    ..Such a cascade of events is hypothesized, in this article, to occur in neurodegenerative conditions such as Parkinson's and Alzheimer's disease...
  34. ncbi Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice
    Ning Xia
    Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany
    J Pharmacol Exp Ther 335:149-54. 2010
    ..This novel mechanism (reversal of eNOS uncoupling) might contribute to the protective effects of resveratrol...
  35. 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) ..
  36. 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...
  37. ncbi Reversal of inducible nitric oxide synthase uncoupling unmasks tolerance to ischemia/reperfusion injury in the diabetic rat heart
    Toru Okazaki
    Second Department of Internal Medicine, Kansai Medical University, Moriguchi City, Japan
    J Mol Cell Cardiol 50:534-44. 2011
    ..These results suggest that the inhibition of iNOS uncoupling unmasks tolerance to I/R injury through enhanced protein S-nitrosylation in the diabetic rat heart...
  38. ncbi Tetrahydrobiopterin: regulator of endothelial nitric oxide synthase in vascular disease
    Keith M Channon
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
    Trends Cardiovasc Med 14:323-7. 2004
    ..Targeting BH4 may provide new therapeutic strategies in vascular disease...
  39. pmc Tetrahydrobiopterin has a glucose-lowering effect by suppressing hepatic gluconeogenesis in an endothelial nitric oxide synthase-dependent manner in diabetic mice
    Abulizi Abudukadier
    Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Diabetes 62:3033-43. 2013
    ..Taken together, BH4 suppresses hepatic gluconeogenesis in an eNOS-dependent manner, and BH4 has a glucose-lowering effect as well as an insulin-sensitizing effect in diabetic mice. BH4 has potential in the treatment of type 2 diabetes. ..
  40. 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-..
  41. pmc Antihypertensive therapy increases tetrahydrobiopterin levels and NO/cGMP signaling in small arteries of angiotensin II-infused hypertensive rats
    Kyu Tae Kang
    Vascular Biology Center, CB 3213, Medical College of Georgia, Augusta, GA 30912, USA
    Am J Physiol Heart Circ Physiol 300:H718-24. 2011
    ..In conclusion, antihypertensive therapy regulates NO/cGMP signaling in small arteries through increasing BH(4) levels and NOS3 phosphorylation at Ser1177...
  42. pmc Using change in plasma phenylalanine concentrations and ability to liberalize diet to classify responsiveness to tetrahydrobiopterin therapy in patients with phenylketonuria
    Rani H Singh
    Department of Human Genetics, Emory University School of Medicine, Decatur, GA 30033, USA
    Mol Genet Metab 104:485-91. 2011
    ..Diet liberalization is an essential component of BH(4)-responsiveness classification...
  43. ncbi Tetrahydrobiopterin (BH4) in PKU: effect on dietary treatment, metabolic control, and quality of life
    B Ziesch
    University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany
    J Inherit Metab Dis 35:983-92. 2012
    ..Tetrahydrobiopterin (BH(4))-sensitive phenylketonuria (PKU) can be treated with sapropterin dihydrochloride. We studied metabolic control and health-related quality of life (HRQoL) in PKU patients treated with BH(4)...
  44. ncbi 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...
  45. pmc Intracellular formation of "undisruptable" dimers of inducible nitric oxide synthase
    Pawel J Kolodziejski
    Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 100:14263-8. 2003
    ..This unanticipated finding revises our understanding of the mechanisms of iNOS dimerization and lays the groundwork for future studies aimed at modulating iNOS activity in vivo...
  46. ncbi Brain biopterin and tyrosine hydroxylase in asymptomatic dopa-responsive dystonia
    Yoshiaki Furukawa
    Movement Disorders Research Laboratory, Centre for Addiction and Mental Health Clarke Division, Toronto, Ontario, Canada
    Ann Neurol 51:637-41. 2002
    It is assumed that brain biopterin and dopamine loss should not be as severe in asymptomatic dopa-responsive dystonia caused by GCH1 mutations as it is in symptomatic dopa-responsive dystonia...
  47. pmc Decreased tetrahydrobiopterin and disrupted association of Hsp90 with eNOS by hyperglycemia impair myocardial ischemic preconditioning
    Nikolina Vladic
    Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Am J Physiol Heart Circ Physiol 301:H2130-9. 2011
    ..The results suggest that eNOS dysregulation may be a central mechanism of impaired cardioprotection during hyperglycemia...
  48. ncbi Regulation of eNOS-derived superoxide by endogenous methylarginines
    Lawrence J Druhan
    Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA
    Biochemistry 47:7256-63. 2008
    ..These observations have important implications with regard to the therapeutic use of l-arginine and the methylarginine-NOS inhibitors in the treatment of disease...
  49. ncbi Endothelial GTPCH in eNOS uncoupling and atherosclerosis
    Tohru Fukai
    Arterioscler Thromb Vasc Biol 27:1493-5. 2007
  50. ncbi Tetrahydrobiopterin in nitric oxide synthase
    Jesús Tejero
    Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA
    IUBMB Life 65:358-65. 2013
    ..In this review, we summarize our current knowledge about the role of tetrahydrobiopterin in the structure, function, and catalytic mechanism of NOS enzymes...
  51. 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...
  52. ncbi Sepiapterin attenuates 1-methyl-4-phenylpyridinium-induced apoptosis in neuroblastoma cells transfected with neuronal NOS: role of tetrahydrobiopterin, nitric oxide, and proteasome activation
    Tiesong Shang
    Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Free Radic Biol Med 39:1059-74. 2005
    ..Implications of BH4 depletion in dopaminergic cells and sepiapterin supplementation to augment the striatal nNOS activity in the pathogenesis mechanism and treatment of Parkinson disease are discussed...
  53. 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
    ....
  54. pmc Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms
    Julien Amour
    Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Anesthesiology 112:576-85. 2010
    ..The authors tested the hypothesis that hyperglycemia abolishes anesthetic preconditioning (APC) through BH4- and heat shock protein 90-dependent pathways...
  55. 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...
  56. ncbi Profound biopterin oxidation and protein tyrosine nitration in tissues of ApoE-null mice on an atherogenic diet: contribution of inducible nitric oxide synthase
    Rita K Upmacis
    Center of Vascular Biology, Department of Pathology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Am J Physiol Heart Circ Physiol 293:H2878-87. 2007
    ..Since BH(4) oxidation can switch the predominant NOS product from NO to superoxide, we predict that progressive NOS uncoupling is likely to drive atherogenic vascular dysfunctions...
  57. ncbi Novel pharmacological chaperones that correct phenylketonuria in mice
    Sandra Santos-Sierra
    Sections of Biochemical and Clinical Pharmacology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria
    Hum Mol Genet 21:1877-87. 2012
    ..Notably, benzylhydantoin was twice as effective as tetrahydrobiopterin. In conclusion, we identified two PCs with high in vivo efficacy that may be further developed into a more effective drug treatment of PKU...
  58. 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)...
  59. 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 ..
  60. 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...
  61. 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...
  62. 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.
  63. 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...
  64. 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...
  65. 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...
  66. 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...
  67. 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
    ....
  68. 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...
  69. 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, ..
  70. 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...
  71. 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...
  72. 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...
  73. ncbi 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...
  74. 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...
  75. 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...
  76. 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.
  77. 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...
  78. 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...
  79. 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...
  80. 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...
  81. 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
    ....
  82. pmc Predicted effects of missense mutations on native-state stability account for phenotypic outcome in phenylketonuria, a paradigm of misfolding diseases
    Angel L Pey
    Department of Biomedicine, University of Bergen, Bergen, Norway
    Am J Hum Genet 81:1006-24. 2007
    ..However, additional factors must be considered that may contribute to the patient phenotype, such as possible effects on catalysis and interindividual differences in physiological and metabolic processes...
  83. ncbi Augmented BH4 by gene transfer restores nitric oxide synthase function in hyperglycemic human endothelial cells
    Shijie Cai
    Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
    Cardiovasc Res 65:823-31. 2005
    ..HAEC were cultured in media with low glucose (5 mM) or high glucose (30 mM)...
  84. ncbi Beneficial effects of exogenous tetrahydrobiopterin on left ventricular remodeling after myocardial infarction in rats: the possible role of oxidative stress caused by uncoupled endothelial nitric oxide synthase
    Tomoya Masano
    Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
    Circ J 72:1512-9. 2008
    ..The uncoupled eNOS generates superoxide rather than NO. The possible role of ROS generated by eNOS in ventricular remodeling after MI was investigated...
  85. 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...
  86. 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
    ....
  87. 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...
  88. ncbi Tetrahydrobiopterin: a novel antihypertensive therapy
    M Porkert
    Division of Cardiology, Emory University, Atlanta, GA, USA
    J Hum Hypertens 22:401-7. 2008
    ....
  89. ncbi 1-Methyl-4-phenylpyridinium-induced apoptosis in cerebellar granule neurons is mediated by transferrin receptor iron-dependent depletion of tetrahydrobiopterin and neuronal nitric-oxide synthase-derived superoxide
    Tiesong Shang
    Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, 53226, USA
    J Biol Chem 279:19099-112. 2004
    ..Implications of these results in unraveling the molecular mechanisms of neurodegenerative diseases (Parkinson's and Alzheimer's disease) are discussed...
  90. ncbi Tetrahydrobiopterin attenuates microvascular reperfusion injury following murine pancreas transplantation
    M Maglione
    Department of General and Transplant Surgery, D Swarovski Research Laboratory, Austria
    Am J Transplant 6:1551-9. 2006
    ..01). BH4 treatment significantly reduces post-ischemic deterioration of microcirculation as well as histologic damage and might be a promising novel strategy in attenuating IRI following pancreas transplantation...
  91. ncbi Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension
    Eberhard Schulz
    II Medizinische Klinik, Mainz, Kardiologie, Angiologie und Internistische Intensivmedizin, Mainz, Germany
    Antioxid Redox Signal 10:1115-26. 2008
    ..The present review will summarize current concepts concerning eNOS uncoupling, with special focus on the role of tetrahydrobiopterin in mediating eNOS uncoupling...
  92. 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...
  93. 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...
  94. 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...
  95. 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...
  96. 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...
  97. 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...
  98. 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...
  99. ncbi 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...
  100. 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
    ....
  101. 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...

Research Grants62

  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. 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%...
  3. Lithium Effects on Tetrahydrobiopterin Deficit in GHC1-Associated Bipolar Disorde
    JAMES DONALD CLELLAND; Fiscal Year: 2010
    ..We have observed that patients with psychiatric disorders (including BPD) have a deficit of plasma total biopterin (a measure of BH4) compared to control subjects, that appears to be alleviated via lithium (Li) treatment...
  4. 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. ..
  5. TENTH INTERNATIONAL SYMPOSIUM ON PTERIDINES
    Madhavan Nair; Fiscal Year: 1992
    ..The symposium will be held at Perdido Beach, Alabama in March of 1993. Folic acid, Antifolates and Biopterin derivatives are the most extensively investigates Pteridines...
  6. 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.
  7. 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...
  8. 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...
  9. 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...
  10. Biopterin Deficit in Schizophrenia: Genetic Dissection of BH4 Biosynthesis.
    JAMES CLELLAND; Fiscal Year: 2008
    ..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...
  11. 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. ..
  12. Tetrahydrobiopterin in Hypoxia-Ischemia Induced Fetal Brain Dysfunction
    Jeannette Vasquez Vivar; Fiscal Year: 2008
    ..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. [unreadable] [unreadable] [unreadable]..
  13. 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 ..
  14. Stem Cell-Mediated Liver Repopulation for Murine PKU
    Cary Harding; Fiscal Year: 2006
    ..The overall goal of the project is to explore HSC-mediated liver repopulation as treatment for rare inborn errors of metabolism using murine PKU as a model system. [unreadable] [unreadable] [unreadable]..
  15. Role of Acetaldehyde in Alcoholic Cardiomyopathy
    Jun Ren; Fiscal Year: 2008
    ..Our long-term goal is to establish the toxic mechanism of acetaldehyde in the development of alcoholic cardiomyopathy so that prevention and treatment can be optimized [unreadable] [unreadable]..
  16. Intravenous non-viral gene therapy for phenylketonuria (PKU)
    Cary Harding; Fiscal Year: 2006
    ..co-administration of 3 separate plasmid vectors encoding single genes. These preclinical trials will form the basis for the development of future clinical trials in humans with PKU. [unreadable] [unreadable] [unreadable] [unreadable]..
  17. Molecular Neurobiology of Drug Abuse
    DONALD KUHN; Fiscal Year: 2006
    ..Kuhn will remain extensively engaged in scientific mentoring activities. ..
  18. Methamphetamine Neurotoxicity and Microglial Activation
    DONALD KUHN; Fiscal Year: 2009
    ..A better understanding of the mechanisms by which METH causes persistent damage to the DA neuronal system could lead to more targeted therapies and would open newer lines of investigation into this and other neurotoxic drugs of abuse. ..
  19. AAV2/8 vector-mediated liver gene therapy for phenylketonuria (PKU)
    Cary Harding; Fiscal Year: 2009
    ..We propose that lessons learned from the treatment of murine PKU will ultimately be applicable to the treatment of human PKU and other allied IEM. ..
  20. NEUROSCIENCE TRAINING IN DRUG ABUSE
    DONALD KUHN; Fiscal Year: 2004
    ..abstract_text> ..
  21. MICROARRAY ANALYSIS OF HUMAN COCAINE ADDICTS
    DONALD KUHN; Fiscal Year: 2002
    ..Microarray-based scanning of the human genome has the potential to establish those genes or gene clusters that define the addictive phenotype, leading the way to proteomic-based studies of the bases of addiction. ..
  22. PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
    DONALD KUHN; Fiscal Year: 2002
    ....
  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...
  24. 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. ..
  25. 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. ..
  26. Anaplerotic therapy in Propionic Acidemia
    Nicola Longo; Fiscal Year: 2008
    ..This approach, if effective, could be extended to a number of other diseases, including other organic acidemias and mitochondrial disorders. [unreadable] [unreadable] [unreadable]..
  27. Arginine and Ovine Model for Fetal Growth Restriction
    Guoyao Wu; Fiscal Year: 2007
    ..This will ultimately promote favorable pregnancy outcomes while saving billions of healthcare dollars in the U.S. and worldwide. [unreadable] [unreadable] [unreadable]..
  28. Molybdenum Pterin-Dithiolene Complexes for Model Studies of the Catalytic Site of
    SHARON BURGMAYER; Fiscal Year: 2007
    ..The goal of this project is to gain a more detailed understanding of how the unique ligand environment of molybdenum in molybdoenzymes is critical to the enzyme activity. [unreadable] [unreadable] [unreadable]..
  29. TETRAHYDROBIOPTERIN BIOSYNTHESIS BY DOPAMINE NEURONS
    Gregory Kapatos; Fiscal Year: 2008
    ..We expect that this multidisciplinary approach will yield important new information on the role of GCH1 in NSDA neuron function and will lead to a new understanding of DRD and familial and idiopathic PD. ..
  30. THE CARNITINE TRANSPORTER IN HUMAN DISEASE
    Nicola Longo; Fiscal Year: 2010
    ....
  31. Newborn screening for PKU and BH4 responsiveness
    Steven Dobrowolski; Fiscal Year: 2008
    ..High resolution melt profiling will play a role to identify BH4 responsive PKU patients. ..
  32. EPR Imaging of Brain O2 in Drug Abuse
    Gerald Rosen; Fiscal Year: 2008
    ..This grant is designed to develop EPR imaging as a tool to study the effects of drugs of abuse on brain oxygen use, which may be critical to understanding brain dysfunction in drug abusing humans. [unreadable] [unreadable] [unreadable]..
  33. Tetrahydrobiopterin: Regulator of Endothelial Function
    ZVONIMIR KATUSIC; Fiscal Year: 2009
    ..This information may help to develop new strategies in prevention and treatment of endothelial dysfunction. . ..
  34. Post-Operative Adhesions: Roles of Hypoxia in Nitric Oxide
    Ghassan Saed; Fiscal Year: 2009
    ..This, in turn, is expected to lead to innovative, new approaches to the prevention and treatment of peritoneal adhesions. ..
  35. BIOCHEMISTRY AND HEPATIC TOXICITY OF CARBON RADICALS
    Paul Ortiz de Montellano; Fiscal Year: 2008
    ..abstract_text> ..
  36. RESPONSE OF PHENYLKETONURIA TO TETRAHYDROBIOPTERIN (BH4)
    Reuben Matalon; Fiscal Year: 2007
    ..Abstract Not Provided ..
  37. Genotype Analysis for Diagnosis of Urea Cycle Disorders
    Steven Dobrowolski; Fiscal Year: 2007
    ..The proposed assay panels provide a means to readily assess gene that are well established to contribute to hyperammonemia. [unreadable] [unreadable] [unreadable]..
  38. FASEB Summer Research Conference on Lysophospholipid Mediators in Health & Diseas
    Sarah Spiegel; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  39. Pharmacokinetics and Metabolic Effects of Folic Acid
    JUNE AYLING; Fiscal Year: 2004
    ..Identifying this particular population of individuals may allow treatment of hyperhomocysteinemia to be more fully optimized. ..
  40. Response to Iron Treatment for Restless Leg Syndrome
    Christopher Earley; Fiscal Year: 2004
    ..An expected finding that IV iron reduces the brain iron insufficiency and dramatically reduces the RLS symptoms strongly supports our model of RLS caused by brain iron insufficiency. ..
  41. DETERMINING THE GENETICS OF RESTLESS LEGS SYNDROME
    Christopher Earley; Fiscal Year: 2003
    ....
  42. SPHINGOLIPID METABOLITE, SPHINGOSINE 1 PHOSPHATE
    Sarah Spiegel; Fiscal Year: 2002
    ..This proposal provides a new paradigm for dissecting the complex interplay between intra and extracellular actions of sphingosine-1-phosphate. ..
  43. NOS-INDEPENDENT NO PRODUCTION IN THE NERVOUS SYSTEM
    Leonid Moroz; Fiscal Year: 2002
    ..Thus, significant gains can be made in our understanding of the synthesis of this gaseous messenger in the brain. This work will also contribute to our understanding of the neural functions in normal and pathological conditions. ..
  44. DOPAMINERGIC FUNCTION IN RESTLESS LEGS SYNDROME
    Christopher Earley; Fiscal Year: 2001
    ..The authors would also explore relationships between iron and CSF measures of dopaminergic activities, which could provide the basis for entirely new research and treatment approaches to RLS. ..
  45. KNOCKOUT MODEL FOR CANAVAN DISEASE
    Reuben Matalon; Fiscal Year: 2001
    ..5) The knock-out mouse will be used in future studies for determining the metabolic role of NAA in brain, for experimentation with enzyme therapy and gene therapy. ..
  46. EXTRACELLULAR SUPEROXIDE DISMUTASE AND ATHEROSCLEROSIS
    David Harrison; Fiscal Year: 2001
    ....
  47. Mentored Patient-Oriented Research Career Development Aw
    IVAN ROBBINS; Fiscal Year: 2004
    ..These studies will advance our knowledge of the mechanism of action of epoprostenol and pulmonary hypertension. ..
  48. Arg199: key player in electron transfer in NOS enzyme
    Valentin Gogonea; Fiscal Year: 2004
    ..Primary focus is placed on how Arg199 modulates the electron transfer in NOS a role only revealed during the dynamics of the system. ..
  49. 4000 Q TRAP LC/MS/MS shared mass spectrometer
    Sarah Spiegel; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  50. Experimental Uveal Melanoma and Ocular Immune Privilege
    KYLE MCKENNA; Fiscal Year: 2007
    ..abstract_text> ..
  51. Structure Biology and Targeted Drug Design for AIDS
    Paul Ortiz de Montellano; Fiscal Year: 2006
    ....
  52. Dopamine and Iron in Restless Legs Syndrome
    Christopher Earley; Fiscal Year: 2006
    ..Using CSF and MRI measurements of iron will assess the CNS iron status. RLS severity will be based on subjective (rating scale and diary) and objective (PSG) measurements. ..
  53. MICROCIRCULATORY PROTECTION IN LATE PRECONDITIONING
    Wei Wang; Fiscal Year: 2001
    ..The third series of experiments will determine if microvascular protection induced by adenosine, nitric oxide, protein kinase C activation, or by IP, is dependent on the activation of iNOS. ..
  54. Polymer-linked Nitroxides Tumor-MRI Contrast Agents.
    Gerald Rosen; Fiscal Year: 2005
    ..Results from these studies will pave the way for the development of novel HPMA copolymer-linked nitroxides for MR imaging of solid tumors and concurrent monitoring of targeted cancer chemotherapy. ..
  55. FilmArray-A Closed System for Multi-Pathogen Screening
    Steven Dobrowolski; Fiscal Year: 2005
    ..Pouches are designed to assay for candidate infectious agents consistent with clinical presentation. ..
  56. Nitric Oxide-Superoxide in Lipid Induced Vascular Diseas
    ZVONIMIR KATUSIC; Fiscal Year: 2005
    ....
  57. Analysis of ATP7B in Screening for Wilson Disease
    Steven Dobrowolski; Fiscal Year: 2004
    ..Prospective screening for WD improves efficacy of treatment and quality of life for affected patients. Genotyping is the best option to confirm results based upon ceruloplasmin analysis in asymptomatic patients. ..
  58. CEREBAL ARTERIAL ADVENTITIA AND VASOSPASM
    ZVONIMIR KATUSIC; Fiscal Year: 2001
    ..Our studies will also expand the knowledge base concerning the vascular biology of adventitia, and its role as a target for transfer and expression of therapeutically beneficial recombinant proteins. ..