Yang C S, Smith T, Ishizaki H, Hong J Y
Department of Chemical Biology & Pharmacognosy, College of Pharmacy, Rutgers University, Piscataway, NJ.
IARC Sci Publ. 1991(105):265-74.
Many nitrosamines are metabolized by cytochromes P450, one of which (P450IIE1) has received much attention because of its role in the metabolic activation of N-nitrosodimethylamine. This enzyme exists in man, rat, mouse, hamster and other animal species. It is inducible by fasting, diabetes and exposure to ethanol, acetone, isoniazid, benzene and other chemicals. P450IIE1 is responsible for the low Km form of N-nitrosodimethylamine demethylase and is the major enzyme catalysing the metabolic activation of this carcinogen. In addition, P450IIE1 is the most active P450 species known in the metabolism of N-nitrosoethylmethylamine and N-nitrosopyrrolidine. In the metabolism of N-nitrosobutylmethylamine, P450IIE1 preferentially oxidizes the methyl group over the butyl group, whereas P450IIB1 efficiently oxidizes both the methyl and butyl groups. P450IIB1 also catalyses the alpha-oxygenation of both the pentyl and methyl groups of N-nitrosopentylmethylamine, forming pentaldehyde and formaldehyde at a rate ratio of 2:1, as well as oxygenation at other carbons of the pentyl group. Many nitrosamines are effectively activated in nonhepatic target tissues. The metabolism of 4-(N-nitroso-methylamino)-1-(3-pyridyl)-1-butanone in lung and nasal microsomes is discussed.
许多亚硝胺由细胞色素P450代谢，其中一种（P450IIE1）因其在N-亚硝基二甲胺代谢活化中的作用而备受关注。这种酶存在于人类、大鼠、小鼠、仓鼠和其他动物物种中。它可被禁食、糖尿病以及接触乙醇、丙酮、异烟肼、苯和其他化学物质诱导。P450IIE1是N-亚硝基二甲胺脱甲基酶的低Km形式的负责酶，并且是催化这种致癌物代谢活化的主要酶。此外，P450IIE1是已知在N-亚硝基乙甲胺和N-亚硝基吡咯烷代谢中最具活性的P450种类。在N-亚硝基丁甲胺的代谢中，P450IIE1优先氧化甲基而非丁基，而P450IIB1能有效氧化甲基和丁基。P450IIB1还催化N-亚硝基戊甲胺的戊基和甲基的α-氧化，以2:1的速率比形成戊醛和甲醛，以及戊基其他碳位的氧化。许多亚硝胺在非肝靶组织中能有效活化。本文讨论了4-（N-亚硝基甲基氨基）-1-（3-吡啶基）-1-丁酮在肺和鼻微粒体中的代谢。
