Influence of cytochrome b5 on the stoichiometry of the different oxidative reactions catalyzed by liver microsomal cytochrome P-450.
Stoichiometries of oxygen and NADPH consumption and product and hydrogen peroxide formation are examined for three forms of cytochrome P-450, LM2, RLM2, and RLM5, using several different substrates. As reported earlier, during the metabolism of some substrates [Gorsky, Koop, and Coon: J. Biol. Chem. 259, 6812-6817 (1984)], excess NADPH and oxygen are consumed suggesting that a 4-electron reduction of oxygen to water occurs. Similar effects are seen with testosterone as substrate for the constitutive forms of P-450, RLM2 and RLM5. However, when aminopyrine or p-nitroanisole serve as substrate, none of the forms of P-450 consumed excess NADPH or oxygen. Thus, consumption of excess NADPH and oxygen appears to be the result of the substrate used. Cytochrome b5 stimulates turnover of LM2 and RLM5 but not RLM2. With LM2, it causes a metabolic switching to occur between the monooxygenase and the NADPH-oxidase reaction. Although RLM5 is also stimulated by cytochrome b5, no metabolic switching occurs. Cytochrome b5 did not affect the proportion of excess NADPH or oxygen consumed.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D003573:Cytochrome b Group / Q000494:pharmacology*; D015786:Cytochromes b5; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats
D003573:Cytochrome b Group; D009249:NADP; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System