Kinetics of the inhibition of mitochondrial respiration by NO

The kinetics of the inhibition of mitochondrial respiration by NO was examined in isolated mitochondria (here obtained from rat brown adipose tissue). The K i of NO for the inhibition was ∼27 nM; the IC 50 of NO increased in proportion to the square of an increase in O 2 tension. The K m of O 2 for respiration was ∼16 μM; in the presence of NO, the dependence of respiration on O 2 tension had a Hill coefficient of ∼2. The unusual kinetics is probably related to the ability of cytochrome c oxidase to use 2 NO or 1 O 2 as electron acceptor. The interaction between NO and O 2 in the control of respiration could be described by the formula V O 2 (O 2, NO)= V O 2 max·([O 2] 2/((16 μM·(1+[NO]/27 nM)) 2+[O 2] 2)). Thus, the kinetics is such that respiration in the presence of physiological levels of NO is very sensitive to decreasing O 2 tension.