Effect of oxygen concentration on NO and O2- production in mitochondria.

ALVAREZ, S.; VALDEZ, L.B.; LORES ARNAIZ, S.; ZAOBORNYJ, T. ; BOVERIS, A.

San Diego, California

Congreso; 7th Annual Meeting of the Oxygen Society; 2000

The Oxygen Society

Nitric oxide (NO) is a free radical produced during the oxidation of L-arginine to L-citrulline, in the presence of NADPH and O2. In mitochondria, this reaction is catalized by mtNOS. Moreover, mitochondria are an important source of superoxide anion (O2-), formed by ubisemiquinone autoxidation. The aim of this work was to study the effect of oxygen concentration on NO and O2- metabolism in mitochondria from rat liver, brain and kidney; and to calculate the steady state concentration of this species and peroxynitrite (ONOO-). The production and steady state concentrations of NO and O2- increased with O2. The O2- production rate was higher than NO production at all O2 concentrations and organs tested. At 20 uM O2 and in liver mitochondria the NO and O2- production (in nmol/min.mg prot.) were 0.13 +/- 0.01 and 1.0 +/- 0.1, respectively. The calculated ONOO- production rate was 0.17 uM s-1. The steady state concentrations for NO, O2- and ONOO- at 20 uM O2 and in liver mitochondria were 26 pM, 0.35 pM and 3 pM, respectively. In hyperoxia, both NO and O2-concentrations increase and a higher ONOO- steady state concentration seems to lead to mitochondrial dysfunction.