期刊
FREE RADICAL RESEARCH
卷 37, 期 2, 页码 121-127出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/1071576021000040655
关键词
tetrahydrobiopterin; endothelium; electron paramagnetic resonance; spin trapping; superoxide
Tetrahydrobiopterin (BH4) is a ubiquitous pteridine metabolite that serves as a NOS cofactor. Recently, we showed that BH4 efficiently inhibits superoxide generation from the heme group at the oxygenase domain of eNOS. This role indicates that BH4 acts as a redox switch in the catalytic mechanism of the enzyme, which may have important consequences in the physiology of the endothelium. Here the mechanism by which BH4 inhibits superoxide release from eNOS and the uncoupling effects of oxidized BH4 metabolites are presented. The implications of the disparate actions of fully reduced and oxidized BH4 metabolites in the control of eNOS biochemistry are discussed in the light of clinical data indicating that BH4 levels are important in the regulation of superoxide levels and of endothelial reactivity.
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