MOLECULAR-BIOLOGY OF RAT STEROID 11-BETA-HYDROXYLASE [P450(11-BETA)] AND ALDOSTERONE SYNTHASE [P450(11-BETA, ALDO)]

The molecular features of rat steroid 11-beta-hydroxylase [P450(11-beta)] and aldosterone synthase [P450(11-beta, aldo)] are discussed. P450(11-beta) is biosynthesized as a precursor form composed of 499 amino acids, having a 24-amino acid extension peptide. Two species of P450(11-beta, aldo) were identified; a precursor form of P450(11-beta, aldo)-1 is 510 amino acids long and has a 34-amino acid extension peptide, while that of P450(11-beta, aldo)-2 is 500 amino acids long and has a 24-amino acid extension peptide. The 286th amino acid of P450(11-beta, aldo)-1 is Glu, while that of P450(11-beta, aldo)-2 is Lys. The cDNA-expression studies showed that P450(11-beta, aldo)-1 had the aldosterone producing activity whereas P450(11-beta, aldo)-2 had no activity, suggesting that Glu286 of P450(11-beta, aldo) plays an important role in the catalysis. The amino acid sequence of a region in P450(11-beta) from Leu337 through Pro352 is highly conserved among the steroidogenic P450s. Functional expression studies on the cDNAs for two P450(11-beta)s showed that P450(11-beta) catalyzes the 11-beta-, 18- and 19-hydroxylations of 11-deoxycorticosterone, but not the aldosterone synthesis. P450(11-beta, aldo), on the other hand, catalyzes the conversion of 11-deoxycorticosterone to corticosterone, 18-hydroxycorticosterone and aldosterone. The two P450(11-beta)s were also shown to catalyze the conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol and cortisone.