RESUMEN
This mini-review will reflect the perspective of its author on two fields of research, which have merged as the result of the insights of investigators whose work has influenced both areas immeasurably. It cannot be overlooked, however, that the research activities of many during a period of over five decades have produced the chemical and biological bases for the exciting discoveries now encompassing the cytochromes P450 and their redox partners, and the three isoforms of nitric oxide synthase as they function in their respective biological milieux. Following the remarkable discovery that, indeed, molecular oxygen can be adducted to organic molecules by enzymatic systems and that such processes require a supply of reducing equivalents, it is the purpose of this review to provide a chart, with some of its detours, of the road that followed in the pursuit of interesting biological phenomena involving these two major oxygenation systems. It is not intended to be a balanced review and apologies must be offered in advance to those whose contributions may be overlooked or simply were not directly germane to the development of the author's journey.
Asunto(s)
NADPH-Ferrihemoproteína Reductasa/química , NADPH-Ferrihemoproteína Reductasa/historia , Óxido Nítrico Sintasa/química , Óxido Nítrico Sintasa/historia , Animales , Historia del Siglo XX , Historia del Siglo XXI , HumanosRESUMEN
NADPH-cytochrome P450 reductase (CPR) and the nitric oxide synthase (NOS) reductase domains are members of the FAD-FMN family of proteins. The FAD accepts two reducing equivalents from NADPH (dehydrogenase flavin) and FMN acts as a one-electron carrier (flavodoxin-type flavin) for the transfer from NADPH to the heme protein, in which the FMNH*/FMNH2 couple donates electrons to cytochrome P450 at constant oxidation-reduction potential. Although the interflavin electron transfer between FAD and FMN is not strictly regulated in CPR, electron transfer is activated in neuronal NOS reductase domain upon binding calmodulin (CaM), in which the CaM-bound activated form can function by a similar mechanism to that of CPR. The oxygenated form and spin state of substrate-bound cytochrome P450 in perfused rat liver are also discussed in terms of stepwise one-electron transfer from CPR. This review provides a historical perspective of the microsomal mixed-function oxidases including CPR and P450. In addition, a new model for the redox-linked conformational changes during the catalytic cycle for both CPR and NOS reductase domain is also discussed.