Tetrahydrobiopterin and nitric oxide: mechanistic and pharmacological aspects.
In previous minireviews in this journal, we discussed work on induction of tetrahydrobiopterin biosynthesis by cytokines and its significance for nitric oxide (NO) production of intact cells as well as functions of H4-biopterin identified at this time for NO synthases (Proc Soc Exp Biol Med 203: 1-12, 1993; Proc Soc Exp Biol Med 219: 171-182, 1998). Meanwhile, the recognition of the importance of tetrahydrobiopterin for NO formation has led to new insights into complex biological processes and revealed possible novel pharmacological strategies to intervene in certain pathological conditions. Recent work could also establish that tetrahydrobiopterin, in addition to its allosteric effects, is redox-active in the NO synthase reaction. In this review, we summarize the current view of how tetrahydrobiopterin functions in the generation of NO and focus on pharmacological aspects of tetrahydrobiopterin availability with emphasis on endothelial function.
Werner
Ernst R
ER
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, A-6020 Innsbruck, Austria. ernst.r.werner@uibk.ac.at
Gorren
Antonius C F
AC
Heller
Regine
R
Werner-Felmayer
Gabriele
G
Mayer
Bernd
B
D000494:Allosteric Regulation; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology*; D002384:Catalysis; D003920:Diabetes Mellitus / Q000378:metabolism; D004579:Electron Transport; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
D004791:Enzyme Inhibitors; D001708:Biopterins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C003402:sapropterin; D001205:Ascorbic Acid