Journal
EXPERIMENTAL BIOLOGY AND MEDICINE
Volume 228, Issue 11, Pages 1291-1302Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/153537020322801108
Keywords
tetrahydrobiopterin; nitric oxide synthase; endothelial dysfunction; reaction mechanism
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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 H-4-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.
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