Interactions of hepatic cytochromes P-450 with steroid hormones. Regioselectivity and stereospecificity of steroid metabolism and hormonal regulation of rat P-450 enzyme expression.
Interactions of hepatic cytochromes P-450 with steroid hormones. Regioselectivity and stereospecificity of steroid metabolism and hormonal regulation of rat P-450 enzyme expression.
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DOI：
10.1016/0006-2952(88)90756-3
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发表时间：
1988
影响因子：
5.8
通讯作者：
D. Waxman
中科院分区：
文献类型：
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作者：
D. Waxman
内质网结合的F-450细胞色素在真核细胞中亲脂性物质的氧化代谢中起着重要作用。在哺乳动物系统中，微粒体P450在肝组织中特别突出，在那里它们催化其结构多样的亲脂性底物的NADP~-依赖性单加氧，以产生极性（例如羟基化）衍生物。许多内源性类固醇和脂肪酸被这些细胞色素羟基化，大量外来化合物也是如此，包括药物和环境化学品[1 -4]。在类固醇激素的情况下，羟基化可导致失活和消除，或者可导致产生具有改变的激素性质的衍生物。在药物和其他化学品的情况下，羟基化通常会导致失活，但在某些情况下会导致形成反应性衍生物，这些衍生物是母体化合物的化学治疗，诱变或致癌特性的原因（方案I）[5，6]。P-450在肝脏中催化类固醇和外源性物质的生物转化有多种途径，这些途径受许多环境和激素因素的调节。肝细胞色素P-450氧化的亲脂性化合物范围广泛，部分反映了P-450血红素蛋白存在多种形式（同工酶）。至少有二十个不同的P-450
Endoplasmi~ reticula-bound F-450 cytochromes play a central role in the oxidative metabolism of lipophili~~ ompo~ ds in eukaryotic celis. In mammalian systems, the microsomal P450s are particularly prominent in hepatic tissue, where they catalyze an NADP~-dependent monooxygenation of their structurally diverse lipophilic substrates to yield polar (eg hydroxylated) derivatives. Many endogenous steroids and fatty acids are hydroxylated by these cytochromes, as are a large number of foreign compounds, including drugs and environmental chemicals [l-4]. In the case of steroid hormones, hydroxylation can lead to deactivation and elimination, or alternatively, may result in production of derivatives that have altered hormonal properties. In the case of drugs and other chemicals, hydroxylation often results in deactivation, but in some instances leads to formation of reactive derivatives that are responsible for the chemotherapeutic, mutagenic or carcinogenic properties of the parent compound (Scheme I)[5, 6]. There are multiple pathways for P-450-catalyzed steroid and xenobiotic biotransformation in the liver, and these pathways are modulated and regulated by a large number of en~ ronmental and hormonal factors, The broad range of lipophilic compounds oxygenated by hepatic cytochrome P-450 in part reflects the presence of multiple forms (isozymes) of the P-450 hemeprotein. At least twenty distinct P-450