Matsunaga T, Iwawaki Y, Watanabe K, Yamamoto I, Kageyama T, Yoshimura H
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa.
J Biochem. 1996 Apr;119(4):617-25. doi: 10.1093/oxfordjournals.jbchem.a021287.
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.
9-蒽醛（9-AA）在猴肝中氧化生成9-蒽甲酸的活性主要位于微粒体。该反应需要NADPH作为必需的辅因子，并且受到SKF 525-A、甲吡酮、双硫仑和CO的显著抑制，这些都是微粒体醛氧化酶（MALDO）的有效抑制剂。分别从未经处理的雄性和雌性日本猴的肝微粒体中纯化出两种介导9-AA氧化生物转化的细胞色素P450同工酶，命名为P450JM-A和P450JM-C。在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳上，这些同工酶各自显示出一条分子量为51,000的条带。P450JM-A和P450JM-C的NH2末端氨基酸序列分别与属于CYP2A和CYP2B亚家族的几种P450的序列高度同源。抗P450JM-C抗体显著抑制猴肝中的9-AA MALDO活性，但抗P450JM-A抗体则无此作用。针对CYP2C11的抗体也抑制了该活性，CYP2C11是雄性大鼠肝中负责9-AA MALDO的主要同工酶。这些结果表明，P450JM-C和与CYP2C11免疫相关的同工酶主要具有针对9-AA的MALDO活性。
