Molecular genetic studies on the biosynthesis of aldosterone in humans.
Corticosterone methyl oxidase Type I (CMO I) and II (CMO II) have been postulated to be the enzymes involved in the final two steps of aldosterone biosynthesis in humans. We have isolated human cDNAs for P450c11 and P450c18 as well as the corresponding genes, CYP11B1 and CYP11B2. Both protein products of these two genes as expressed in COS-7 cells exhibit steroid 11β-hydroxylase activity, but only P450c18, a product of CYP11B2, carried steroid 18-hydroxylase activity to form aldosterone. These results indicate that CYP11B2 encodes CMO, the actual catalytic function of which is retained by P450c18, a multifunctional enzyme. This conclusion is further supported by the finding that the P450c18 gene, CYP11B2, is mutated at several different loci in patients deficient in CMO I or II.
Department of Medical Chemistry, Kochi Medical School, Nankoku, Kochi 783, Japan.
Y
Y
Shizuta
T
T
Kawamoto
Y
Y
Mitsuuchi
K
K
Toda
K
K
Miyahara
Y
Y
Ichikawa
H
H
Imura
S
S
Ulick
D000302:Adrenal Cortex / Q000201:enzymology* / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D055162:Biocatalysis; D019556:COS Cells; D002522:Chlorocebus aethiops; D019405:Cytochrome P-450 CYP11B2 / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D050505:Mutant Proteins; D011994:Recombinant Proteins; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; C033112:corticosterone methyl oxidase I; C025352:corticosterone methyl oxidase II