PODEROSO Juan Jose
capítulos de libros
Regulation of oxygen metabolism by nitric oxide
BOVERIS A, PODEROSO JJ
Nitric Oxide: Biology and Pathobiology
Año: 2000; p. 355 - 368
A classic physiological paradigm was the stability of molecular oxygen (o2) uptake up to very low hypoxic o2 tensions. The notion was supported by the very low km for o2, of mitochondrial cytochrome oxidase. Recently, nitric oxide was shown to reversibly 1nhiblt cytochrome oxidase after binding to,the enzyme with even greater afflnlty than o2, hence, o2 uptake became dependent on the o2:no ratio. To define a regulatory mechanlsm, it was further required that a fast dissociation of no-cytochrome complex following remotion of no could occur. Accordingly, we observed that no elicits a stoichlometrical prepduction of superoxide anion in mitochondria by reactlng with membrane-bound ubiquinol; con-sequently, no largely decays and inhlbltion of cytochrome oxidase is released through the oxidatlve route of formatlon of peroxynitrite, the product of the reaction of no and superoxide radical. The overall mechanism is llkely a metabolic pathway common to many physiological purposes emerging from the existence of dlfferent nitic oxide synthase lsoforms.