title: Cytochrome b5: novel roles in steroidogenesis.
abstract: Cytochrome b(5) (cyt-b(5)) is essential for the regulation of steroidogenesis and as such has been implicated in a number of clinical conditions. It is well documented that this small hemoprotein augments the 17,20-lyase activity of cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1). Studies have revealed that this augmentation is accomplished by cyt-b(5) enhancing the interaction between cytochrome P450 reductase (POR) and CYP17A1. In this paper we present evidence that cyt-b(5) induces a conformational change in CYP17A1, in addition to facilitating the interaction between CYP17A1 and POR. We also review the recently published finding that cyt-b(5) allosterically augments the activity of 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3βHSD), a non cytochrome P450 enzyme, by increasing the enzymes affinity for its cofactor, NAD(+). The physiological importance of this finding, in terms of understanding adrenal androstenedione production, is examined. Finally, evidence that cyt-b(5) is able to form homomeric complexes in living cells is presented and discussed.
authors.affiliation: Department of Biochemistry, University of Stellenbosch, Stellenbosch 7602, South Africa.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Storbeck
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Swart
authors.forename: Pierre
authors.initials: P
authors.lastname: Goosen
authors.forename: Pieter
authors.initials: P
authors.lastname: Swart
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000735:Androstenedione / Q000096:biosynthesis; D015786:Cytochromes b5 / Q000378:metabolism*; D006801:Humans; D009243:NAD / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis*
chemical_list: D013256:Steroids; D009243:NAD; D000735:Androstenedione; D015786:Cytochromes b5; D015096:3-Hydroxysteroid Dehydrogenases; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D009251:NADPH-Ferrihemoprotein Reductase