Polymorphism of cytochrome P-450 in humans.
Polymorphism of cytochrome P-450 in humans.
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DOI：
10.1016/0165-6147(89)90207-1
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发表时间：
1989-03
影响因子：
13.8
通讯作者：
F. Guengerich
中科院分区：
文献类型：
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作者：
F. Guengerich
许多不同的细胞色素P-450蛋白质存在于人类肝脏和其他组织中。这些酶氧化药物和致癌物质以及内源性化学物质，如类固醇和类花生酸。正如Peter Guengerich解释的那样，由于遗传和环境的影响，个体细胞色素P-450酶的活性在个体之间存在差异;在某些情况下，其机制是已知的。细胞色素P-450（Cytochrome P-450，P-450）酶催化药物、致癌物和其他外源性物质的氧化，也催化体内内源性化合物的氧化。对实验动物和人类的研究表明，多达20个或更多不同的P-450基因可能在体内同时表达（表I;参考文献14）。有几条证据表明，这些活性在人体内差异很大，个体间差异的后果具有药理学意义。那些以比正常慢的速率代谢药物的人（弱代谢者，或“PM”受试者）将积累母体药物，并且由于增加的药理学反应，任何副作用都将增强;导致毒性产物的次级途径也可能是有利的5s 6。
A number of different cytochrome P-450 proteins are found in human liver and other tissues. These enzymes oxidize drugs and carcinogens as well as endogenous chemicals such as steroids and eicosanoids. As Peter Guengerich explains, activities of individual cytochrome P-450 enzymes vary among individuals as a result of both genetic and environmental influences; in some cases, the mechanisms are known. Such variation can have major influences in determining drug toxicity, inborn errors of steroid metabolism, and possibly cancer risk.Cytochrome P-450 (P-450) enzymes catalyse the oxidation of drugs, carcinogens and other xenobiotics in addition to compounds endogenous to the body. Studies with experimental animals and with humans suggest that as many as 20 or more different P-450 genes may be expressed in the body at one time (Table I; Refs 14). Several lines of evidence suggest that the activities vary widely in humans and that the consequences of interindividual variation are of pharmacological importance. Those who metabolize drugs at slower rates than normal (poor metabolizers, or ‘PM’subjects) will accumulate the parent drug and any sideeffects will be enhanced because of increased pharmacological response; secondary pathways leading to toxic products may also be favored5s6.