Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

The role of tetrahydrobiopterin in superoxide generation from eNOS: enzymology and physiological implications. Free Radic Res 2003 Feb;37(2):121-7

Date

03/26/2003

Pubmed ID

12653200

DOI

10.1080/1071576021000040655

Abstract

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.

Author List

Vásquez-Vivar J, Kalyanaraman B, Martásek P

Authors

Balaraman Kalyanaraman PhD Chair, Professor in the Biophysics department at Medical College of Wisconsin
Jeannette M. Vasquez-Vivar PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antioxidants
Biopterin
Catalysis
Electron Spin Resonance Spectroscopy
Humans
Models, Biological
Models, Chemical
Nitric Oxide Synthase
Nitric Oxide Synthase Type III
Protein Binding
Protein Structure, Tertiary
Spin Trapping
Superoxides
jenkins-FCD Prod-398 336d56a365602aa89dcc112f077233607d6a5abc