Nitric oxide and oxygen metabolism.

Introduction Inhibition of mitochondrial respiration has been associated with the cytotoxicity of NO right from the beginning of NO research [1,2]. Recent findings have confirmed the importance of mitochondrial inhibition, but put the previous research into a new context. Here we review our findings that: (a) NO reversibly inhibits O2 consumption by isolated cytochrome oxidase, mitochondria, nerve terminals and cells; (b) NO causes glutamate release from brain nerve terminals probably by inhibiting cytochrome oxidase; (c) cultured astrocytes expressing the inducible form of NO synthase (iNOS) reversibly inhibit their own respiration via the inhibition of cytochrome oxidase; (d) mitochondria cause NO breakdown; (e) NO reversibly inhibits catalase; ( f ) NO and H202 react with superoxide dismutase (SOD) to produce peroxynitrite; (g) the reaction between NO and oxyhaemoglobin is much slower in intact blood than in blood after the membranes have been lysed.