Microsomal aldehyde oxygenase (MALDO): purification and characterization of a cytochrome P450 isozyme responsible for oxidation of 9-anthraldehyde to 9-anthracenecarboxylic acid in monkey liver.

Oxidative activity of 9-anthraldehyde (9-AA) to 9-anthracenecarboxylic acid in monkey liver was mainly located in microsomes. The reaction required NADPH as an essential cofactor and was significantly inhibited by SKF 525-A, metyrapone, disulfiram, and CO, potent inhibitors of microsomal aldehyde oxygenase (MALDO). Two cytochrome P450 isozymes, named P450JM-A and P450JM-C, which mediate the oxidative biotransformation of 9-AA were purified from hepatic microsomes of untreated male and female Japanese monkeys, respectively. These isozymes each showed a single band of molecular mass 51,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The NH2-terminal amino acid sequences of P450JM-A and P450JM-C are highly homologous with those of several P450s belonging to the CYP2A and CYP2B subfamilies, respectively. The anti-P450JM-C antibody significantly suppressed 9-AA MALDO activity in monkey liver, but anti-P450JM-A antibody did not. The antibody against CYP2C11, which is a major isozyme responsible for 9-AA MALDO in male rat liver, also inhibited the activity. These results indicate that P450JM-C and isozyme(s) immunologically related to CYP2C11 predominantly possess MALDO activity toward 9-AA.