Differential dependence on NADPH concentrations of two microsomal corticosteroid 21-hydroxylation reactions

The dependency on NADPH concentrations of the bovine adrenal cortex microsomal 21-hydroxylation of progesterone and of 17-hydroxyprogesterone was investigated. The average Km for NADPH in the 21-hydroxylation of progesterone is 10.4 muM while that for the 21-hydroxylation of 17-hydroxyprogesterone is 0.6 muM. The optimal NADPH concentrations for these two hydroxylations are, in average, one order of magnitude apart. The different affinities of the two 21-hydroxylating activities with respect to NADPH may indicate the presence of independent 21-hydroxylation reactions for these two steroid substrates. This evidence is consistent with the observed genetic data in human congenital adrenal hyperplasia.