Cytochrome P450 11B2, mitochondrial

Definition:

A cytochrome P450 monooxygenase that catalyzes the biosynthesis of adrenal mineralocorticoid aldosterone. Catalyzes three sequential oxidative reactions of 11-deoxycorticosterone/21-hydroxyprogesterone, namely 11-beta hydroxylation followed with two successive oxidations at C18 to yield 18-hydroxy and then 18-aldehyde derivatives, resulting in the formation of aldosterone. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin).

References:

[1]. Natallia Strushkevich, et al. Structural insights into aldosterone synthase substrate specificity and targeted inhibition. Mol Endocrinol. 2013 Feb;27(2):315-24. [Content Brief]

[2]. Stephanie Bechtel, et al. The effect of amino-acid substitutions I112P, D147E and K152N in CYP11B2 on the catalytic activities of the enzyme. Eur J Biochem. 2002 Feb;269(4):1118-27. [Content Brief]

[3]. L Pascoe, et al. Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4996-5000. [Content Brief]

[4]. S Portrat-Doyen, et al. Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene. J Clin Endocrinol Metab. 1998 Nov;83(11):4156-61. [Content Brief]

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