Neonatal cytochrome P450 CYP3A7: A comprehensive review of its role in development, disease, and xenobiotic metabolism

Arch Biochem Biophys. 2019 Sep 30:673:108078. doi: 10.1016/j.abb.2019.108078. Epub 2019 Aug 22.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Base Sequence
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism*
  • Cytochrome P-450 CYP3A Inhibitors / pharmacology
  • Disease*
  • Growth and Development*
  • Humans
  • Infant, Newborn
  • Xenobiotics / metabolism*

Substances

  • Cytochrome P-450 CYP3A Inhibitors
  • Xenobiotics
  • CYP3A7 protein, human
  • Cytochrome P-450 CYP3A