Cytochrome b5 modulates multiple reactions in steroidogenesis by diverse mechanisms

Cytochrome b(5) (cyt-b(5)) 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-b(5) 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 3 beta HSD by increasing the affinity of 3 beta HSD for its cofactor NAD(+). We review the modulation of CYP17A1 and 3 beta HSD activity by cyt-b(5) and discuss the reaction mechanisms associated with each activity. The physiological importance of cyt-b(5) in regulating mammalian steroidogenesis is presented and the impact of inactivating cyt-b(5) mutations are reviewed. This article is part of a Special Issue entitled 'Steroid/Sterol signaling'. (C) 2014 Elsevier Ltd. All rights reserved.