Cytochrome P-450 inactivation: structure of the prosthetic heme adduct with propyne.
Cytochrome P-450 inactivation: structure of the prosthetic heme adduct with propyne.
复制标题
细胞色素 P-450 失活：人工血红素与丙炔加合物的结构。
DOI：
10.1021/bi00528a033
复制
发表时间：
1981
期刊：
影响因子：
2.9
通讯作者：
Kunze,KL
中科院分区：
文献类型：
--
作者：
OrtizdeMontellano,PR;Kunze,KL
Paul R. Ortiz de Montellano*·* 和 Kent L. Kunze 摘要：苯巴比妥预处理大鼠的肝微粒体细胞色素 P-450 在烟酰胺腺嘌呤二核苷酸依赖过程中被丙炔破坏，这也会导致体内异常绿卟啉的积累。绿卟啉已通过其电子吸收、质谱和核磁共振特性被鉴定为 N-(2-氧代-丙基)原卟啉 IX 的异构体，其中烷基化氮是吡咯环 A 的氮。肝微粒体细胞色素 P-450 中其他氮的烷基化在烯烃催化加工过程中被破坏（De Matteis，1971，1978；Levin 等） al.，1972；Ortiz de Montellano & Mico，1980）、乙炔（White & Miiller-Eberhard，1977；Ortiz de Montellano & Kunze，1980a）和外星人（Ortiz de Montellano & Kunze，1980b）。细胞色素 P-450 酶的自杀性 X 键代谢似乎是破坏过程的基础，尽管其自杀性质仅在 2-异丙基-4-戊烯酰胺的情况下得到明确记录（Ortiz de Montellano & Mico，1981）。单取代烯烃和乙炔对酶的破坏伴随着微粒体血红素含量大约等摩尔的减少（De Matteis，1971；Bradshaw 等人，1978；White，1978），并且同时出现异常肝绿卟啉（De Matteis，1978；White & Miiller-Eberhard，1977；Ortiz de蒙特利亚诺和昆泽，1980a；奥尔蒂斯·德蒙特利亚诺和米科，
Paul R. Ortiz de Montellano*·* and Kent L. Kunze abstract: Hepatic microsomal cytochrome P-450 from phenobarbital-pretreated rats is destroyed by propyne in a reduced nicotinamide adenine dinucleotide dependent process which also results in vivo in the accumulation of an abnormal green porphyrin. The green porphyrin has been identified by its electronic absorption, mass spectrometric, and nuclear magnetic resonance properties as the isomer of N-(2-oxo-propyl) protoporphyrin IX in which the alkylated nitrogen is that of pyrrole ring A. Alkylation of the other nitrogens inHepatic microsomal cytochrome P-450 is destroyed during catalytic processing of olefins (De Matteis, 1971, 1978; Levin et al., 1972; Ortiz de Montellano & Mico, 1980), acetylenes (White & Miiller-Eberhard, 1977; Ortiz de Montellano & Kunze, 1980a), and alienes (Ortiz de Montellano & Kunze, 1980b). Suicidal x-bond metabolism by the cytochrome P-450 enzyme appears to underlie the destructive process, although its suicidal nature has only been explicitly documented in the case of 2-isopropyl-4-pentenamide (Ortiz de Montellano & Mico, 1981). The destruction of the enzyme by monosubstituted olefins and acetylenes is paralleledby an approximately equimolar decrease in microsomal heme content (De Matteis, 1971; Bradshaw et al., 1978; White, 1978) and by the con-current appearance of abnormal hepatic green porphyrins (De Matteis, 1978; White & Miiller-Eberhard, 1977; Ortiz de Montellano & Kunze, 1980a; Ortiz de Montellano & Mico,