Figure 1.

Adrenal steroid biosynthesis pathways and enzymatic defects causing CAH. The enzymes and proteins required for normal cortisol synthesis are shown: StAR, the steroid acute regulatory protein; CYP11A1, cholesterol side chain cleavage enzyme or P450scc; CYP17A1, steroid 17-hydroxylase/17,20-lyase or P450c17; 3βHSD2, 3β-hydroxysteroid dehydrogenase/isomerase type 2; POR, P450-oxidoreductase; and CYP21A2, steroid 21-hydroxylase or P450c21. Also shown are Fdx and FdxR, ferredoxin and ferredoxin reductase, respectively, which are the electron transfer proteins for the mitochondrial cytochrome P450 enzymes in the CYP11 family; SULT2A1, steroid sulfotransferase type 2A1 or DHEA sulfotransferase; and STS, steroid sulfatase. The 19-carbon androgen precursors DHEA and DHEAS are metabolized to active androgens and estrogens via other enzymes in the adrenal and peripheral tissues. Dotted line from 17OHP to AD indicates poor conversion by human CYP17A1, even in the presence of cytochrome b₅ (b₅), compared to conversion of 17OH-pregnenolone (17-hydroxypregnenolone) to DHEA.