Li A P, Kaminski D L, Rasmussen A
Surgical Research Institute, St. Louis University Health Sciences Center, MO 63167, USA.
Toxicology. 1995 Dec 15;104(1-3):1-8. doi: 10.1016/0300-483x(95)03155-9.
Cytochrome P450 isozyme 3A4 (CYP3A4) is a major isozyme in the human liver and is known to metabolize a larger variety of xenobiotics and endogenous biochemicals. The identities of CYP3A4 substrates are summarized here. A total of 32 chemicals belonging to different structural classes have been evaluated and found to be substrates for CYP3A4. The metabolic pathways for these substrates include N-oxidation, C-oxidation, N-dealkylation, O-dealkylation, nitro-reduction, dehydration, and C-hydroxylation. While the major experimental system used to elucidate the role of CYP3A4 in the metabolic transformation of these substrates is the human liver microsome system, cultured human hepatocytes and yeast/cultured cells genetically engineered to express CYP3A4 are also employed by the different investigators. The common approaches to identify the role of CYP3A4 are also summarized, which include correlation of metabolic activity of the substrates studied with those for known CYP3A4-catalyzed substrates, correlation of activity with CYP3A4 content, inhibition of activity with CYP3A4 specific antibodies, inhibition of activity with known CYP3A4 substrates and inhibitors, induction of activity with CYP3A4 inducers and demonstration of activity with purified CYP3A4 enzyme.
细胞色素P450同工酶3A4（CYP3A4）是人类肝脏中的一种主要同工酶，已知它能代谢多种外源性物质和内源性生化物质。本文总结了CYP3A4的底物。共有32种属于不同结构类别的化学物质经过评估，被发现是CYP3A4的底物。这些底物的代谢途径包括N-氧化、C-氧化、N-脱烷基化、O-脱烷基化、硝基还原、脱水和C-羟基化。虽然用于阐明CYP3A4在这些底物代谢转化中作用的主要实验系统是人类肝微粒体系统，但不同研究者也采用了培养的人类肝细胞以及经过基因工程改造以表达CYP3A4的酵母/培养细胞。本文还总结了确定CYP3A4作用的常用方法，包括将所研究底物的代谢活性与已知CYP3A4催化底物的代谢活性进行关联、将活性与CYP3A4含量进行关联、用CYP3A4特异性抗体抑制活性、用已知CYP3A4底物和抑制剂抑制活性、用CYP3A4诱导剂诱导活性以及用纯化的CYP3A4酶证明活性。
