Cytochrome b5 modulates multiple reactions in steroidogenesis by diverse mechanisms

J Steroid Biochem Mol Biol. 2015 Jul:151:66-73. doi: 10.1016/j.jsbmb.2014.11.024. Epub 2014 Nov 23.

Abstract

Cytochrome b5 (cyt-b5) is a relatively small haemoprotein which plays an important role in the regulation of mammalian steroidogenesis. This unique protein has the ability to modulate the activity of key steroidogenic enzymes via a number of diverse reaction mechanisms. Cyt-b5 can augment the 17,20-lyase activity of CYP17A1 by promoting the interaction of CYP17A1 and POR; enhance the 16-ene-synthase activity of CYP17A1 by acting as an electron donor; and enhance the activity of 3βHSD by increasing the affinity of 3βHSD for its cofactor NAD(+). We review the modulation of CYP17A1 and 3βHSD activity by cyt-b5 and discuss the reaction mechanisms associated with each activity. The physiological importance of cyt-b5 in regulating mammalian steroidogenesis is presented and the impact of inactivating cyt-b5 mutations are reviewed. This article is part of a Special Issue entitled 'Steroid/Sterol signaling'.

Keywords: 16-ene-synthase; 3β-hydroxysteroid dehydrogenase; 3βHSD; CYP17A1; Cytochrome P450 17-hydroxylase/17,20-lyase; Cytochrome b(5).

Publication types

  • Review

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / metabolism
  • Adrenal Hyperplasia, Congenital / enzymology
  • Adrenal Hyperplasia, Congenital / genetics
  • Animals
  • Cytochromes b5 / genetics
  • Cytochromes b5 / metabolism*
  • Humans
  • Mutation
  • NAD / metabolism
  • Steroid 17-alpha-Hydroxylase / metabolism*
  • Steroids / biosynthesis

Substances

  • Steroids
  • NAD
  • Cytochromes b5
  • 3-Hydroxysteroid Dehydrogenases
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase