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* Institute for Medical Chemistry and Biochemistry, University of Innsbruck, A-6020 Innsbruck, Austria;
Institute for Pharmacology and Toxicology, University of Graz, A-8010 Graz, Austria;
Institute for Molecular Cell Biology, University of Jena, D-07740 Jena, Germany
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.
Key Words: tetrahydrobiopterin • nitric oxide synthase • endothelial dysfunction • reaction mechanism
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