Using fluorescence optical and electron spin resonance spectroscopy, m
e have investigated the production of superoxide by bovine endothelial
nitric oxide synthase (NOS), In contrast to neuronal NOS, the heme mo
iety is identified as the exclusive source of superoxide production by
endothelial NOS. Thus, calmodulin-mediated enzyme regulation affects
production of nitric oxide and superoxide simultaneously and inseparab
ly. Tbt balance between the nitric oxide/superoxide reaction pathways
may be shifted by addition of exogenous heme-specific agents, such as
tetrahydrobiopterin. Our results have direct relevance for the pathoph
ysiology of atherosclerosis. (C) 1998 Federation of European Biochemic
al Societies.