Defective CYP11B2 does not oxidise 18HCORST

Stable Identifier
Reaction [transition]
Homo sapiens
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Cytochrome P450 11B2, mitochondrial (CYP11B2 aka aldosterone hydroxylase) is an enzyme necessary for aldosterone biosynthesis via corticosterone (CORST) and 18-hydroxycorticosterone (18HCORST). Defects in CYP11B2 result in disorders of aldosterone synthesis. Corticosterone methyloxidase 1 and 2 deficiencies (CMO-1; MIM:203400 and CMO-2 deficiency; MIM:61060) are autosomal recessive disorders of aldosterone biosynthesis. In CMO-1 deficiency, aldosterone is undetectable in plasma, while its immediate precursor, 18HCORST, is low or normal. Mutations causing CMO-1 deficiency include L461P, E255* and a 6bp duplication resulting in Arg and Leu insertion at codon 142 (Nomoto et al. 1997, Peter et al. 1997, Kayes-Wandover et al. 2001 respectively). In CMO-2 deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18HCORST. Patients with CMO-2 deficiency have elevated plasma 18-hydroxycorticosterone/aldosterone ratios. Missense mutations causing CMO-2 deficiency include T185I, T498A, T185I, R181W and V386A (Peter et al. 1998, Dunlop et al. 2003, Pascoe et al. 1992).
Literature References
PubMed ID Title Journal Year
1594605 Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency

Rösler, A, Pascoe, L, White, PC, Curnow, KM, Slutsker, L

Proc. Natl. Acad. Sci. U.S.A. 1992
11238478 Type 1 aldosterone synthase deficiency presenting in a middle-aged man

Kayes-Wandover, KM, White, PC, Schindler, RE, Taylor, HC

J. Clin. Endocrinol. Metab. 2001
9360501 Hereditary defect in biosynthesis of aldosterone: aldosterone synthase deficiency 1964-1997

Drop, SL, Visser, HK, Peter, M, Fawaz, L, Sippell, WG

J. Clin. Endocrinol. Metab. 1997
12788848 A compound heterozygote case of type II aldosterone synthase deficiency

Crock, PA, Montalto, J, Curnow, KM, Dunlop, FM, Funder, JW

J. Clin. Endocrinol. Metab. 2003
9625333 Mutation THR-185 ILE is associated with corticosterone methyl oxidase deficiency type II

Sólyom, J, Bünger, K, Peter, M, Sippell, WG

Eur. J. Pediatr. 1998
9177280 CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450C18)

Shizuta, Y, Hashimoto, K, Nagano, I, Ishimura, Y, Massa, G, Doi, Y, Yamashiro, T, Mitani, F, Miyahara, K, Ogoshi, S, Fukata, J, Nomoto, S, Imura, H, Onishi, S, Toda, K

Biochem. Biophys. Res. Commun. 1997
Catalyst Activity

steroid hydroxylase activity of CYP11B2 mutants [mitochondrial inner membrane]

Normal reaction
Functional status

Loss of function of CYP11B2 mutants [mitochondrial inner membrane]

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