药物在分离的肝细胞中引起的外源性血红素类似物的N-烷基化。所得卟啉的结构异构和手性。
N-alkylation of exogenous haem analogues caused by drugs in isolated hepatocytes. Structural isomerism and chirality of the resulting porphyrins.
作者信息
De Matteis F, Harvey C, Martin S R
出版信息
Biochem J. 1986 Aug 15;238(1):263-8. doi: 10.1042/bj2380263.
Abstract
Isolated rat hepatocytes incubated with two suicide substrates of cytochrome P-450, 2-allyl-2-isopropylacetamide and 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine(4-ethyl-DD C), convert exogenous mesohaem and deuterohaem into N-alkylated mesoporphyrins and deuteroporphyrins respectively. The N-alkylated mesoporphyrins can be separated by h.p.l.c. from the corresponding N-alkylated protoporphyrins originating from endogenous haem; in this way the contribution of both endogenous and exogenous pools of haem can be studied in the same experiment. N-Alkylated mesoporphyrin exhibits chiral properties, and its isomeric composition and/or amount are dependent on the particular cytochrome P-450 enzyme predominating in the cell. These findings provide additional and more direct evidence that exchangeable haem is taken up by cytochrome P-450 before being N-alkylated.
摘要
将分离出的大鼠肝细胞与细胞色素P-450的两种自杀底物（2-烯丙基-2-异丙基乙酰胺和3,5-二乙氧基羰基-4-乙基-1,4-二氢-2,6-二甲基吡啶（4-乙基-DDC））一起孵育，它们会分别将外源性中卟啉和氘代卟啉转化为N-烷基化中卟啉和氘代卟啉。N-烷基化中卟啉可以通过高效液相色谱法与源自内源性血红素的相应N-烷基化原卟啉分离；通过这种方式，可以在同一实验中研究内源性和外源性血红素池的贡献。N-烷基化中卟啉具有手性特性，其异构体组成和/或数量取决于细胞中占主导地位的特定细胞色素P-450酶。这些发现提供了额外且更直接的证据，表明可交换的血红素在被N-烷基化之前被细胞色素P-450摄取。
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本文引用的文献
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Experimental hepatic porphyria caused by feeding 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine. Comparison with sedormid porphyria.喂食3,5 - 二乙氧羰基 - 1,4 - 二氢 - 2,4,6 - 三甲基吡啶引起的实验性肝性卟啉症。与速可眠卟啉症的比较。
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