Meta-Biol

• Pathways

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).