Kinetics of the inhibition of mitochondrial respiration by NO

Abstract

The kinetics of the inhibition of mitochondrial respiration by NO was examined in isolated mitochondria (here obtained from rat brown adipose tissue). The Ki of NO for the inhibition was approximately 27 nM; the IC50 of NO increased in proportion to the square of an increase in O2 tension. The Km of O2 for respiration was approximately 16 microM; in the presence of NO, the dependence of respiration on O2 tension had a Hill coefficient of approximately 2. The unusual kinetics is probably related to the ability of cytochrome c oxidase to use 2 NO or 1 O2 as electron acceptor. The interaction between NO and O2 in the control of respiration could be described by the formula VO2(O2, NO) = VO2max x ([O2]2/((16 microM x (1 + [NO]/27 nM))2 + [O2]2)). Thus, the kinetics is such that respiration in the presence of physiological levels of NO is very sensitive to decreasing O2 tension.