Genomes and Genes
Summary: A natural product that has been considered as a growth factor for some insects.
Publications218 found, 100 shown here
- 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 pathwaysMark 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...
- Reduced infectivity of a Leishmania donovani biopterin transporter genetic mutant and its use as an attenuated strain for vaccinationBarbara Papadopoulou
Centre de Recherche en Infectiologie du Centre de Recherche du CHUL and Division de Microbiologie, , , , Canada
Infect Immun 70:62-8. 2002Pterins are essential for the growth of Leishmania species, and recent work has led to the isolation of the biopterin transporter BT1...
- Altered tetrahydrobiopterin metabolism in atherosclerosis: implications for use of oxidized tetrahydrobiopterin analogues and thiol antioxidantsJeannette 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)...
- 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 expressionMark 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...
- Identification of the gene encoding alkylglycerol monooxygenase defines a third class of tetrahydrobiopterin-dependent enzymesKatrin 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...
- GTP cyclohydrolase I expression, protein, and activity determine intracellular tetrahydrobiopterin levels, independent of GTP cyclohydrolase feedback regulatory protein expressionAmy 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...
- Deficient BH4 production via de novo and salvage pathways regulates NO responses to cytokines in adult cardiac myocytesIrina 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....
- Tetrahydrobiopterin recycling, a key determinant of endothelial nitric-oxide synthase-dependent signaling pathways in cultured vascular endothelial cellsToru 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...
- The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide synthase: an EPR spin trapping studyJeannette 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...
- Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthaseKarel 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...
- Endothelial nitric oxide synthase dysfunction in diabetic mice: importance of tetrahydrobiopterin in eNOS dimerisationS 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...
- Tetrahydrobiopterin biosynthesis, regeneration and functionsB 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...
- Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertensionUlf 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...
- Modeling of biopterin-dependent pathways of eNOS for nitric oxide and superoxide productionSaptarshi 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...
- Physarum polycephalum expresses a dihydropteridine reductase with selectivity for pterin substrates with a 6-(1', 2'-dihydroxypropyl) substitutionClaudia 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...
- Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterinJ 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...
- Endothelial, sympathetic, and cardiac function in inherited (6R)-L-erythro-5,6,7,8-tetrahydro-L-biopterin deficiencyLila Mayahi
Centre for Clinical Pharmacology, University College London, 5 University St, London, UK
Circ Cardiovasc Genet 3:513-22. 20106R)-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...
- Tetrahydrobiopterin: biochemistry and pathophysiologyErnst R Werner
Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck A 6020, Austria
Biochem J 438:397-414. 2011....
- Congenic mapping and genotyping of the tetrahydrobiopterin-deficient hph-1 mouseJeffrey 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...
- Formation of a protonated trihydrobiopterin radical cation in the first reaction cycle of neuronal and endothelial nitric oxide synthase detected by electron paramagnetic resonance spectroscopyP 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+)...
- High affinity S-Adenosylmethionine plasma membrane transporter of Leishmania is a member of the folate biopterin transporter (FBT) familyLarbi 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...
- Suppression of eNOS-derived superoxide by caveolin-1: a biopterin-dependent mechanismKanchana Karuppiah
Department of Anesthesiology, Ohio State University, Columbus, Ohio, USA
Am J Physiol Heart Circ Physiol 301:H903-11. 2011....
- Determination of quinonoid dihydrobiopterin by high-performance liquid chromatography and electrochemical detectionS 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...
- IGF-I alleviates diabetes-induced RhoA activation, eNOS uncoupling, and myocardial dysfunctionJun 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...
- 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 overexpressionJennifer 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...
- Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthaseNermin 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...
- Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitriteMing 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...
- Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthaseTomasz J Guzik
Department of Cardiovascular Medicine, University of Oxford, Oxford, UK
Circulation 105:1656-62. 2002....
- Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOSMark 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) ..
- Glyceryl ether monooxygenase resembles aromatic amino acid hydroxylases in metal ion and tetrahydrobiopterin dependenceKatrin Watschinger
Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Fritz Pregl Str 3 VI, A 6020 Innsbruck, Austria
Biol Chem 390:3-10. 2009....
- Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular diseaseNicholas 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...
- L-Ascorbic acid potentiates nitric oxide synthesis in endothelial cellsR 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...
- 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 activationOle 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...
- Gene transfer of human guanosine 5'-triphosphate cyclohydrolase I restores vascular tetrahydrobiopterin level and endothelial function in low renin hypertensionJie 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...
- NAD(P)H oxidase and uncoupled nitric oxide synthase are major sources of glomerular superoxide in rats with experimental diabetic nephropathyMinoru 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...
- Vascular protection by tetrahydrobiopterin: progress and therapeutic prospectsZvonimir 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...
- HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cellsYoshiyuki 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)...
- Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiencyC 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...
- Adaptation of Leishmania cells to in vitro culture results in a more efficient reduction and transport of biopterinG 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...
- Decrease in tetrahydrobiopterin as a possible cause of nephropathy in type II diabetic ratsM 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...
- A specific role for eNOS-derived reactive oxygen species in atherosclerosis progressionTomofumi 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...
- Structure of nitric oxide synthase oxygenase dimer with pterin and substrateB 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...
- Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal centerC 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...
- L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterinR 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...
- Effect of electroconvulsive therapy on biopterin and large neutral amino acids in severe, medication-resistant depressionR Hoekstra
Department of Psychiatry, University Hospital Rotterdam Dijkzigt, Rotterdam, The Netherlands
Psychiatry Res 103:115-23. 2001b>Biopterin, neopterin and the large neutral amino acids (LNAA), i.e...
- Effect of light therapy on biopterin, neopterin and tryptophan in patients with seasonal affective disorderRocco 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 ..
- The two faces of endothelial nitric oxide synthase in the pathophysiology of atherosclerosisSeinosuke 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...
- Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adultsIratxe 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...
- Inducible nitric oxide synthase: role of the N-terminal beta-hairpin hook and pterin-binding segment in dimerization and tetrahydrobiopterin interactionD 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...
- The effect of high glucose on NO and O2- through endothelial GTPCH1 and NADPH oxidaseQun 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...
- Neopterin, biopterin, and nitric oxide concentrations in the cerebrospinal fluid of children with central nervous system infectionsKohji Azumagawa
Division of Pediatrics, Yao Tokusyu-kai General Hospital, 3-15-38 Kyuhoji, Yao-shi, Osaka 581-0072, Japan
Brain Dev 25:200-2. 2003We measured neopterin, biopterin and nitric oxide (NO) concentrations in the cerebrospinal fluid of pediatric patients with central nervous system (CNS) infectious diseases...
- Tetrahydrobiopterin as combined electron/proton donor in nitric oxide biosynthesis: cryogenic UV-Vis and EPR detection of reaction intermediatesAntonius 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...
- Tetrahydrobiopterin radical enzymologyChin-Chuan Wei
Department of Immunology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
Chem Rev 103:2365-83. 2003
- Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjectsNikolaj 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-..
- Nitric oxide dynamics and endothelial dysfunction in type II model of genetic diabetesMilad 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...
- Esrom, an ortholog of PAM (protein associated with c-myc), regulates pteridine synthesis in the zebrafishSylvie 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...
- GTP cyclohydrolase feedback regulatory protein controls cofactor 6-tetrahydrobiopterin synthesis in the cytosol and in the nucleus of epidermal keratinocytes and melanocytesBhaven 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...
- The pteridine pathway in zebrafish: regulation and specification during the determination of neural crest cell-fateIrmgard Ziegler
GSF Institut für Klinische Molekularbiologie und Tumorgenetik, Munchen, Germany
Pigment Cell Res 16:172-82. 2003....
- 5-Methyltetrahydrofolate and tetrahydrobiopterin can modulate electrotonically mediated endothelium-dependent vascular relaxationTudor 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....
- (6R)-5,6,7,8-tetrahydro-L-biopterin and its stereoisomer prevent ischemia reperfusion injury in human forearmLila 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. 20076R-5,6,7,8-tetrahydro-L-biopterin (6R-BH4) is a cofactor for endothelial nitric oxide synthase but also has antioxidant properties...
- Nitric oxide and biopterin in depression and stressJ G Van Amsterdam
Laboratory of Health Effects Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands
Psychiatry Res 85:33-8. 1999..On the basis of this review, it is suggested that future psychoneuroimmunological research should more fully explore the possible role of tetrahydrobiopterin and nitric oxide in depressive disorders...
- Chemical stabilization of tetrahydrobiopterin by L-ascorbic acid: contribution to placental endothelial nitric oxide synthase activityMiklos Toth
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest 8, P O Box 260, H 1444, Hungary
Mol Hum Reprod 8:271-80. 2002..Moreover, we demonstrated that concentrations of ASC present in the placenta as a common vitamin C supply are sufficient to protect cellular free BH(4) and may contribute to the stimulation of placental eNOS activity...
- Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservationT O Fischmann
Structural Chemistry Department, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
Nat Struct Biol 6:233-42. 1999..The high-resolution, refined structures of eNOS (2.4 A resolution) and iNOS (2.25 A resolution) reveal an unexpected structural zinc situated at the intermolecular interface and coordinated by four cysteines, two from each monomer...
- 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase couplingCharalambos Antoniades
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK
Circulation 114:1193-201. 2006..Rather, 5-MTHF was a strong peroxynitrite scavenger and increased vascular BH4 and the BH4/total biopterin ratio...
- Proteasome-dependent degradation of guanosine 5'-triphosphate cyclohydrolase I causes tetrahydrobiopterin deficiency in diabetes mellitusJian 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....
- Tetrahydrobiopterin uptake in supplemental administration: elevation of tissue tetrahydrobiopterin in mice following uptake of the exogenously oxidized product 7,8-dihydrobiopterin and subsequent reduction by an anti-folate-sensitive processKeiko Sawabe
Department of Biosciences, Teikyo University of Science and Technology, Uenohara, Yamanashi 409 0193, Japan
J Pharmacol Sci 96:124-33. 2004....
- Angiotensin-II-induced oxidative stress elicits hypoadiponectinaemia in ratsY Hattori
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, 321 0293, Japan
Diabetologia 48:1066-74. 2005..We hypothesised that adiponectin levels decrease in response to oxidative stress and that this may promote the development of hypertension, endothelial dysfunction and insulin resistance...
- Lack of nitric oxide mediation of flow-dependent arteriolar dilation in type I diabetes is restored by sepiapterinZsolt Bagi
Department of Pathophysiology, Semmelweis University, Budapest, Hungary
J Vasc Res 40:47-57. 2003....
- The autoxidation of tetrahydrobiopterin revisited. Proof of superoxide formation from reaction of tetrahydrobiopterin with molecular oxygenMichael Kirsch
Institut fur Physiologische Chemie, Universitatsklinikum, Hufelandstrasse 55, D 45122 Essen, Germany
J Biol Chem 278:24481-90. 2003..Conclusively, because H4B can per se induce oxidative stress, an in vivo overproduction of this pterin, as is evident in various diseases, may be responsible for the observed acceleration of pathophysiological pathways...
- Cytokine-stimulated GTP cyclohydrolase I expression in endothelial cells requires coordinated activation of nuclear factor-kappaB and Stat1/Stat3Annong Huang
Evans Memorial Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass 02118, USA
Circ Res 96:164-71. 2005..Thus, IFN-gamma and TNF-alpha exert distinct but cooperative roles for BH4 biosynthesis in endothelium that may have important implications for vascular function during vascular inflammation...
- GTP cyclohydrolase I gene transfer augments intracellular tetrahydrobiopterin in human endothelial cells: effects on nitric oxide synthase activity, protein levels and dimerisationShijie Cai
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK
Cardiovasc Res 55:838-49. 2002..We aimed to investigate the role of BH4 levels in intracellular eNOS regulation, by targeting the BH4 synthetic pathway as a novel strategy to modulate intracellular BH4 levels...
- GCH1 haplotype determines vascular and plasma biopterin availability in coronary artery disease effects on vascular superoxide production and endothelial functionCharalambos Antoniades
Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
J Am Coll Cardiol 52:158-65. 2008....
- Endothelium-specific GTP cyclohydrolase I overexpression attenuates blood pressure progression in salt-sensitive low-renin hypertensionYan hua Du
Department of Pharmacology, Michigan State University, East Lansing, USA
Circulation 117:1045-54. 2008..This study tested the hypothesis that endothelium-specific GTPCH I overexpression retards the progression of hypertension through preservation of the structure and function of resistance mesenteric arteries...
- Myocardial ischemia results in tetrahydrobiopterin (BH4) oxidation with impaired endothelial function ameliorated by BH4Cristian 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...
- Developmental changes in nitric oxide synthesis in the ovine placentaHyukjung Kwon
Department of Animal Science and Center for Animal Biotechnology and Genomics, Texas A and M University, College Station, Texas 77843 2471, USA
Biol Reprod 70:679-86. 2004....
- Effect of 2,4-diamino-6-hydroxy-pyrimidine on postburn Staphylococcus aureus sepsis in ratsHong-Yun Li
Department of Microbiology and Immunology, Trauma Research Center, Postgraduate Medical College, 304th Hospital, Beijing, People's Republic of China
Crit Care Med 30:2520-7. 2002..triphosphate-cyclohydrolase I (GTP-CHI) is the first and rate-limiting enzyme for the de novo biosynthesis of biopterin. The objective of present study was to observe the effect of 2,4-diamino-6-hydroxy-pyrimidine (DAHP), an ..
- Statin enhances cytokine-mediated induction of nitric oxide synthesis in vascular smooth muscle cellsYoshiyuki Hattori
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan
Cardiovasc Res 54:649-58. 2002....
- [The protective effects and its underlying mechanism of 2,4-diamino-6-hydroxy-pyrimidine on postburn Staphylococcus aureus sepsis in rats]Yongming Yao
Burn Institute, The 304th Hospital of PLA, Beijing 100037, P.R. China
Zhonghua Shao Shang Za Zhi 18:84-7. 2002..Furthermore, biopterin (BH(4)) and nitric oxide (NO) levels in these tissue were also measured...
- Nitric oxide (NO) pretreatment increases cytokine-induced NO production in cultured rat hepatocytes by suppressing GTP cyclohydrolase I feedback inhibitory protein level and promoting inducible NO synthase dimerizationJoon-Hong Park
Vascular System Research Center and Department of Molecular and Cellular Biochemistry, Kangwon National University, School of Medicine, Chunchon, Kangwon-do 200-701, Korea
J Biol Chem 277:47073-9. 2002..SNAP pretreatment also increased total cellular levels of biopterin and active iNOS dimer...
- Acute inhibition of guanosine triphosphate cyclohydrolase 1 uncouples endothelial nitric oxide synthase and elevates blood pressureShuangxi Wang
Department of Medicine, Division of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Hypertension 52:484-90. 2008..In conclusion, GTPCH1 via BH4 maintains normal BP and endothelial function in vivo by preserving NO synthesis by eNOS...
- Mechanisms of aging-induced impairment of endothelium-dependent relaxation: role of tetrahydrobiopterinKatherine A Blackwell
Department of Anesthesia Research and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Am J Physiol Heart Circ Physiol 287:H2448-53. 2004..Oxidation of BH4 does not appear to be an important mechanism underlying vasomotor dysfunction in aged mouse arteries...
- Increased endothelial tetrahydrobiopterin synthesis by targeted transgenic GTP-cyclohydrolase I overexpression reduces endothelial dysfunction and atherosclerosis in ApoE-knockout miceNicholas J Alp
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
Arterioscler Thromb Vasc Biol 24:445-50. 2004..We aimed to investigate the importance of endothelial BH4 availability in atherosclerosis using a transgenic mouse model with endothelial-targeted overexpression of the rate-limiting enzyme in BH4 synthesis, GTP-cyclohydrolase I (GTPCH)...
- BH4 responsiveness associated to a PKU mutation with decreased binding affinity for the cofactorCristina Aguado
Centro de Biologia Molecular Severo Ochoa CSIC UAM, Madrid, Spin
Clin Chim Acta 380:8-12. 2007..The molecular basis of the response appears to be multifactorial...
- Pterin interactions with distinct reductase activities of NO synthaseM M Pantke
Department of Pharmacology and Toxicology, , Versbacher Str. 9, , Germany
Biochem J 356:43-51. 2001....
- [NO and hypertension]Yasunobu Hirata
Department of Cardiovascular Medicine, University of Tokyo
Nippon Rinsho 62:243-6. 2004
- Reduced nitric oxide metabolites in CSF of patients with tetrahydrobiopterin deficiencyGiovanna Zorzi
Division of Clinical Chemistry and Biochemistry, University Children's Hospital, Zurich, Switzerland
J Neurochem 80:362-4. 2002..5-5.0 mg/kg tetrahydrobiopterin. Our data indicate impaired NO synthase function in patients with BH4 deficiency and suggest possible involvement in the neuronal cell dysfunction...
- A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactionsLance Swick
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA
J Neurochem 97:1447-55. 2006....
- Inhibition of brain GTP cyclohydrolase I and tetrahydrobiopterin attenuates cerebral infarction via reducing inducible NO synthase and peroxynitrite in ischemic strokeGrant A Kidd
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317, USA
Stroke 36:2705-11. 2005....
- Evaluation of basic performance and applicability of a newly developed in vivo nitric oxide sensorSeiichi Mochizuki
Department of Medical Engineering, Kawasaki Medical School, Okayama, Japan
Physiol Meas 23:261-8. 2002..5 mg NTG caused a measurable increase in plasma NO level (2.0 +/- 2.2 nmol l(-1), mean +/- SD, n = 3). In conclusion, the new NO sensor demonstrated a satisfying performance for both in vitro and in vivo applications...
- Important role of tetrahydrobiopterin in no complex formation and interdomain electron transfer in neuronal nitric-oxide synthaseT Noguchi
Institute for Chemical Reaction Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, 980-8577, Japan
Biochem Biophys Res Commun 282:1092-7. 2001..Thus, our data indicate the importance of the pterin binding to the active site structure during the reduction of the NO-heme complex by NADPH during catalytic turnover...
- In vivo expression of recombinant vascular endothelial growth factor in rabbit carotid artery increases production of superoxide anionOsamu Suda
Department of Anesthesiology, Molecular Pharmacology, and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA
Arterioscler Thromb Vasc Biol 25:506-11. 2005..Superoxide anion appears to be an important mediator of vascular effects of VEGF in vivo...
- [Tetrahydrobiopterin therapy for hyperphenylalaninemia due to phenylalanine hydroxylase deficiency. When and how?]A Baldellou Vazquez
Unidad de Enfermedades Metabolicas, Hospital Infantil Miguel Servet, Zaragoza, Spain
An Pediatr (Barc) 64:146-52. 2006..Consequently, a simple tool to identify which patients are likely candidates for this treatment and how they will progress in the long-term is required...
- Effect of vitamin C on the availability of tetrahydrobiopterin in human endothelial cellsT A Baker
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
J Cardiovasc Pharmacol 37:333-8. 2001..This effect appears to be independent of the ability of vitamin C to scavenge superoxide anions...
- Endothelial GTPCH in eNOS uncoupling and atherosclerosisTohru Fukai
Arterioscler Thromb Vasc Biol 27:1493-5. 2007
- Catalytic reduction of a tetrahydrobiopterin radical within nitric-oxide synthaseChin Chuan Wei
Department of Pathobiology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
J Biol Chem 283:11734-42. 2008..We utilized a freeze-quench instrument, the biopterin analog 5-methyl-H(4)B, and a method that could separately quantify the flavin and pterin radicals that formed in ..
- [Tetrahydrobiopterin and endothelial dysfunction]Jie-Sheng Zheng
Sheng Li Ke Xue Jin Zhan 35:155-8. 2004
- Endothelial dysfunction in heart failure: mechanisms and therapeutic approachesJohann Bauersachs
Medizinische Klinik der Julius Maximilians Universität, Wurzburg, Germany
Curr Vasc Pharmacol 2:115-24. 2004..This article reviews the current knowledge of the pathophysiological events contributing to endothelial dysfunction in CHF as well as several treatment options to reverse those changes...
- Current strategies and perspectives for correcting endothelial dysfunction in atherosclerosisL E Spieker
Cardiovascular Center Cardiology, University Hospital, , Switzerland
J Cardiovasc Pharmacol 38:S35-41. 2001..However, the efficacy of pharmacotherapy aimed at an improvement in endothelial function depends on the individual risk factor profile of the patient...
- Stimulation of tetrahydrobiopterin synthesis by cyclosporin A in mouse brain microvascular endothelial cellsMasakazu Ishii
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Int J Biochem Cell Biol 34:1134-41. 2002..These findings suggest that increase in BH4 content induced by CsA is coupled with NO production by inducible type of NO synthase...
- Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial functionMathew Eric Hyndman
Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1
Am J Physiol Heart Circ Physiol 282:H2167-72. 2002..superoxide) production and improve endothelial function. 5-Methyltetrahydrofolate may represent an important strategy for intervention aimed at improving tetrahydrobiopterin bioavailability...
- Transcribing the cross-talk of cytokine-induced tetrahydrobiopterin synthesis in endothelial cellsTimothy E Peterson
Circ Res 96:141-3. 2005
- DRUG RESISTANCE AND PTERIDINE METABOLISM IN LEISHMANIAStephen 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...
- DRUG RESISTANCE AND PTERIDINE METABOLISM IN LEISHMANIAStephen 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...
- DRUG RESISTANCE AND GENE AMPLIFICATION IN LEISHMANIAStephen 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 ..
- DRUG RESISTANCE AND GENE AMPLIFICATION IN LEISHMANIAStephen 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 ..
- Hsp90, NOS3 and CardioprotectionYang 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%...
- Hsp90, NOS3 and CardioprotectionYang 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%...
- BIOPTERIN, CATECHOLAMINES, & NO IN REGULATING APOPTOSISRobert 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. ..
- EPR Studies of Biological PCET ElementsR Britt; Fiscal Year: 2007..A biopterin radical is transiently formed in the conversion of arginine to NHA, and a similar radical intermediate likely ..
- 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...
- CIRCULATORY SHOCK, NITRIC OXIDE AND TETRAHYDROBIOPTERINSteven 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.
- Redox properties of heme-oxygenase in NO synthasesMekki 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...
- Oxidative Stress and Pteridine Metabolism in DiabetesCynthia 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 ..
- Air Pollution Exposure/Atherosclerosis:Vascular MechanismSanjay 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...
- Structure-Function and Reacation Mechanism of eNOSAh 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...
- Superoxide Generation from eNOS: The Role of PterinsJEANNETTE 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. ..
- Superoxide Generation from eNOS: The Role of PterinsJeannette 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. ..
- Superoxide Generation from eNOS: The Role of PterinsJeannette 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. ..
- Superoxide Generation from eNOS: The Role of PterinsJeannette Vasquez Vivar; Fiscal Year: 2006..abstract_text> ..
- Superoxide Generation from eNOS: The Role of PterinsJeannette Vasquez Vivar; Fiscal Year: 2003..abstract_text> ..
- Tetrahydrobiopterin in Hypoxia-Ischemia Induced Fetal Brain DysfunctionJeannette 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. ..
- iNOS Posttranslational Regulation in Cardiac RejectionGALEN PIEPER; Fiscal Year: 2009..A better understanding of this molecular process may lead to better strategies to prevent injury cardiac cells in these patients. ..
- MOLECULAR TARGETS OF NITRIC OXIDE IN CARDIAC TRANSPLANTSGALEN PIEPER; Fiscal Year: 2004..These studies will provide a novel mechanism to explain the pathogenesis of dyskinesis and graft failure during cardiac transplant rejection. ..
- IGF-1, Oxidative Stress and Cardiovascular AgingJun 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...