Figure 601

Metabolic pathways of corticosteroid biosynthesis.

proceeds from 17a-hydroxyprogesterone and 1-deoxy-cortisol to yield cortisol. Thus, steroid intermediates are converted to steroid end products by sequential 17-, 21-, and 11-hydroxylation reactions. 11-p-Hydroxylation is essential for glucocorticoid and mineralocorticoid activity of a steroid. The steroid hydroxylase system has the characteristics of a mixed-function oxidase, since two substrates, steroid and NADPH, are oxidized. All hydroxylases seem to be associated with a specific cytochrome P450.

The 17- and 21-hydroxylase enzymes are associated with microsomes, whereas the 11-p-hydroxylase has a mitochondrial origin. Since the last-named enzyme is not detectable in other steroid-producing tissues, the term 11-oxygenated steroids is considered synonymous with adrenal steroids. Aldosterone synthesis involves an essential 18-hydroxylation step catalyzed by P450c18 with corticosterone as the precursor; this reaction also takes place within the mitochondria.

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