Sino-German Joint Research Institute Nanchang University, 235 East Nanjing Road, Nanchang, 330047, Jiangxi, PR China.
University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Mail Stop C238, 12850 E. Montview Blvd., Aurora, CO, 80045, USA.
Arch Biochem Biophys. 2019 Sep 30;673:108078. doi: 10.1016/j.abb.2019.108078. Epub 2019 Aug 22.
The human cytochrome P450 CYP3A7, once thought to be an enzyme exclusive to fetal livers, has more recently been identified in neonates and developing infants as old as 24 months post-gestational age. CYP3A7 has been demonstrated to metabolize two endogenous compounds that are known to be important in the growth and development of the fetus and neonate, namely dehydroepiandrosterone sulfate (DHEA-S) and all-trans retinoic acid (atRA). In addition, it is also known to metabolize a variety of drugs and xenobiotics, albeit generally to a lesser extent relative to CYP3A4/5. CYP3A7 is an important component in the development and protection of the fetal liver and additionally plays a role in certain disease states, such as cancer and adrenal hyperplasia. Ultimately, a full understanding of the expression, regulation, and metabolic properties of CYP3A7 is needed to provide neonates with appropriate individualized pharmacotherapy. This article summarizes the current state of knowledge of CYP3A7, including its discovery, distribution, alleles, RNA splicing, expression and regulation, metabolic properties, substrates, and inhibitors.
人类细胞色素 P450 CYP3A7 曾被认为是一种仅存在于胎儿肝脏中的酶，最近在新生儿和发育至出生后 24 个月的婴儿中也被发现。CYP3A7 已被证明可以代谢两种内源性化合物，这两种化合物在胎儿和新生儿的生长发育中非常重要，分别是脱氢表雄酮硫酸酯（DHEA-S）和全反式视黄酸（atRA）。此外，它还已知可以代谢多种药物和外源性物质，尽管相对于 CYP3A4/5 通常程度较小。CYP3A7 是胎儿肝脏发育和保护的重要组成部分，此外在某些疾病状态下也发挥作用，如癌症和肾上腺增生。最终，需要充分了解 CYP3A7 的表达、调节和代谢特性，以对新生儿进行适当的个体化药物治疗。本文总结了 CYP3A7 的现有知识状态，包括其发现、分布、等位基因、RNA 剪接、表达和调节、代谢特性、底物和抑制剂。
