期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1988
卷号：85
期号：8
页码：2514-2517
DOI：10.1073/pnas.85.8.2514
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Two amine N-methyltransferases isolated from rabbit liver catalyze S-adenosylmethionine-dependent N-methylation of benzidine and 4-aminobiphenyl but not of 4-aminoazobenzene or 2-aminobiphenyl. The enzymatic reaction products were analyzed and found to be identical to synthetic N-methylbenzidine and N-methyl-4-aminobiphenyl. N-Methylation may be a critical step in the metabolic activation of primary arylamines because N-methylarylamines, unlike primary arylamines, are readily N-oxygenated by the NADPH- and oxygen-dependent microsomal flavin-containing monooxygenase. Kinetic studies carried out with the purified porcine liver monooxygenase demonstrate that, while activity with primary arylamines could not be detected, N-methyl derivatives of benzidine, 4-aminoazobenzene, and 4-aminobiphenyl are substrates. Products formed from N-methyl-4-aminobiphenyl had the properties of the hydroxylamine and/or nitrone in that the enzyme- and time-dependent incubation product(s) reduced Fe3+ to Fe2+, and formaldehyde was formed during the course of the reaction. These data suggest that N-methyl-4-aminobiphenyl is oxidized to N-hydroxy-N-methyl-4-aminobiphenyl, which can undergo further oxidation to a nitrone that hydrolyzes to formaldehyde and N-hydroxy-4-aminobiphenyl.
