Modulation of aldosterone and cortisol synthesis on the molecular level.
CYP11B1 and the closely related CYP11B2 are involved in the production of adrenal steroid hormones. Although in human their primary structure is 93% identical they are involved in the biosynthesis of functionally diverse products, such as glucocorticoids and mineralocorticoids, respectively. In contrast, bovine CYP11B1 combines both activities in one single enzyme. The CYP11B family belongs to class I cytochromes P450 that have been described in bacteria and mitochondria and receive their electrons from a low molecular weight iron sulphur protein which is reduced by a NADPH-dependent FAD-containing reductase. In this review, we summarise the current knowledge on the modulation of aldosterone and cortisol synthesis by transcriptional regulation, on the molecular level as consequence of mutations found in patients suffering from steroid hormone-related diseases as well as introduced by site-directed mutagenesis and as consequence of protein-protein interaction with both CYP11A1 and the natural redox partner adrenodoxin.
Lisurek
Michael
M
Universität des Saarlandes, FR 8.8 Biochemie, Postfach 151150, 66041 Saarbrücken, Germany.
Bernhardt
Rita
R
D000325:Adrenodoxin / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D010084:Oxidation-Reduction; D011487:Protein Conformation; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics / Q000378:metabolism
D005938:Glucocorticoids; D000325:Adrenodoxin; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D006854:Hydrocortisone