Wright William C, Chenge Jude, Chen Taosheng
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Liver Res. 2019 Dec;3(3-4):132-142. doi: 10.1016/j.livres.2019.08.001. Epub 2019 Aug 29.
Cytochrome P450 enzymes function to catalyze a wide range of reactions, many of which are critically important for drug response. Members of the human cytochrome P450 3A (CYP3A) family are particularly important in drug clearance, and they collectively metabolize more than half of all currently prescribed medications. The ability of these enzymes to bind a large and structurally diverse set of compounds increases the chances of their modulating or facilitating drug metabolism in unfavorable ways. Emerging evidence suggests that individual enzymes in the CYP3A family play discrete and important roles in catalysis and disease progression. Here we review the similarities and differences among CYP3A enzymes with regard to substrate recognition, metabolism, modulation by small molecules, and biological consequence, highlighting some of those with clinical significance. We also present structural perspectives to further characterize the basis of these comparisons.
细胞色素P450酶的功能是催化各种各样的反应，其中许多反应对药物反应至关重要。人类细胞色素P450 3A（CYP3A）家族成员在药物清除方面尤为重要，它们共同代谢目前所有处方药的一半以上。这些酶结合大量结构多样的化合物的能力增加了它们以不利方式调节或促进药物代谢的可能性。新出现的证据表明，CYP3A家族中的个别酶在催化和疾病进展中发挥着独特而重要的作用。在这里，我们综述了CYP3A酶在底物识别、代谢、小分子调节和生物学后果方面的异同，突出了其中一些具有临床意义的方面。我们还从结构角度进一步阐述这些比较的基础。
