Oxygen dependence of mitochondrial nitric oxide synthase activity

ALVAREZ S; VALDEZ LB; LORES ARNAIZ S; ZAOBORNYJ T; BOVERIS A

Biochem Biophys Res Commun

Academic Press, Inc. - Elsevier

Año: 2003 vol. 305 p. 771 - 775

The effect of O2 concentration on mitochondrial nitric oxide synthase (mtNOS) activity and on O2- production was determined in rat liver, brain and kidney submitochondrial membranes. The KmO2 for mtNOS were 40 mM, 73 mM and 37 mM O2 and the Vmax were 0.51, 0.49 and 0.42 nmol NO/min.mg protein for liver, brain and kidney mitochondria, respectively. The rates of O2- production, 0.5-12.8 nmol O2-/min.mg protein, depended on O2 concentration up to 1.1 mM O2. Intramitochondrial NO, O2- and ONOO- steady state concentrations were calculated for the physiological level of 20 mM O2; they were 20-39 nM NO, 0.17-0.33 pM O2-, and 0.6-2.2 nM ONOO- for the three organs. These levels establish O2/NO ratios of 513-1000 that correspond to physiological inhibitions of cytochrome oxidase by intramitochondrial NO of 16 to 25 %. The production of NO by mtNOS appears as a regulatory process that modulates mitochondrial oxygen uptake and cellular energy production.