title: Cytochrome b5 modulates multiple reactions in steroidogenesis by diverse mechanisms.
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'.
authors.affiliation: Department of Biochemistry, University of Stellenbosch, Stellenbosch 7600, South Africa.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Storbeck
authors.affiliation: Department of Biochemistry, University of Stellenbosch, Stellenbosch 7600, South Africa.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Swart
authors.affiliation: Department of Biochemistry, University of Stellenbosch, Stellenbosch 7600, South Africa.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Fox
authors.affiliation: Department of Biochemistry, University of Stellenbosch, Stellenbosch 7600, South Africa. Electronic address: pswart@sun.ac.za.
authors.forename: Pieter
authors.initials: P
authors.lastname: Swart
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology / Q000235:genetics; D000818:Animals; D015786:Cytochromes b5 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D009243:NAD / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis
chemical_list: D013256:Steroids; D009243:NAD; D015786:Cytochromes b5; D015096:3-Hydroxysteroid Dehydrogenases; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase
keywords: 16-ene-synthase; 3β-hydroxysteroid dehydrogenase; 3βHSD; CYP17A1; Cytochrome P450 17-hydroxylase/17,20-lyase; Cytochrome b(5)