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人类环境中异物的代谢。

Metabolism of xenobiotics of human environments.

出版信息

Prog Mol Biol Transl Sci. 2012;112:31-88. doi: 10.1016/B978-0-12-415813-9.00003-9.

Abstract

Xenobiotics have been defined as chemicals to which an organism is exposed that are extrinsic to the normal metabolism of that organism. Without metabolism, many xenobiotics would reach toxic concentrations. Most metabolic activity inside the cell requires energy, cofactors, and enzymes in order to occur. Xenobiotic-metabolizing enzymes can be divided into phase I, phase II, and transporter enzymes. Lipophilic xenobiotics are often first metabolized by phase I enzymes, which function to make xenobiotics more polar and provide sites for conjugation reactions. Phase II enzymes are conjugating enzymes and can directly interact with xenobiotics but more commonly interact with metabolites produced by phase I enzymes. Through both passive and active transport, these more polar metabolites are eliminated. Most xenobiotics are cleared through multiple enzymes and pathways. The relationship between chemical concentrations, enzyme affinity and quantity, and cofactor availability often determine which metabolic reactions dominate in a given individual.

摘要

外源性化学物质被定义为生物体暴露于其中的化学物质,这些化学物质与生物体的正常新陈代谢无关。没有新陈代谢,许多外源性化学物质会达到毒性浓度。大多数细胞内的代谢活动都需要能量、辅助因子和酶才能发生。外源性化学物质代谢酶可以分为 I 相、II 相和转运酶。亲脂性外源性化学物质通常首先被 I 相酶代谢,其作用是使外源性化学物质更具极性,并提供与结合反应的位点。II 相酶是结合酶,可以直接与外源性化学物质相互作用,但更常见的是与 I 相酶产生的代谢物相互作用。通过被动和主动转运,这些极性更大的代谢物被消除。大多数外源性化学物质通过多种酶和途径清除。化学浓度、酶亲和力和数量以及辅助因子可用性之间的关系通常决定了在给定个体中哪种代谢反应占主导地位。

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