Defective CYP11B2 does not oxidise CORST

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).

细胞色素P450 11B2（CYP11B2，又称醛固酮羟化酶）是一种对醛固酮生物合成至关重要的酶，其通过皮质酮（CORST）和18-羟皮质酮（18HCORST）进行醛固酮的生物合成。CYP11B2缺陷会导致醛固酮合成障碍。皮质酮甲氧基化酶1和2缺乏症（CMO-1；MIM：203400和CMO-2缺乏症；MIM：61060）是醛固酮生物合成的常染色体隐性遗传疾病。在CMO-1缺乏症中，血浆中醛固酮无法检测到，而其直接前体18HCORST则呈低或正常水平。导致CMO-1缺乏症的突变包括L461P、E255*以及导致第142密码子Arg和Leu插入的6bp重复（Nomoto等，1997年，Peter等，1997年，Kayes-Wandover等，2001年分别报道）。在CMO-2缺乏症中，醛固酮可能呈低或正常水平，但以18HCORST分泌增加为代价。CMO-2缺乏症患者的血浆中18-羟皮质酮/醛固酮比率升高。导致CMO-2缺乏症的错义突变包括T185I、T498A、T185I、R181W和V386A（Peter等，1998年，Dunlop等，2003年，Pascoe等，1992年报道）。