Biosynthesis of Cholesterol, Steroids, and Isoprenoids:- Steroid Hormones Are Formed by Side-Chain Cleavage and Oxidation of Cholesterol
Humans derive all their steroid hormones from cholesterol (Fig. 21–46). Two classes of steroid hormones are synthesized in the cortex of the adrenal gland: mineralocorticoids, which control the reabsorption of inorganic ions (Na+, Cl+, and HCO-3) by the kidney, and glucocorticoids, which help regulate gluconeogenesis and reduce the inflammatory response. Sex hormones are produced in male and female gonads and the placenta. They include progesterone, which regulates the female reproductive cycle, and androgens (such as testosterone) and estrogens (such as estradiol), which influence the development of secondary sexual characteristics in males and females, respectively. Steroid hormones are effective at very low concentrations and are therefore synthesized in relatively small quantities. In comparison with the bile salts, their production consumes relatively little cholesterol. Synthesis of steroid hormones requires removal of some or all of the carbons in the “side chain” on C-17 of the D ring of cholesterol. Side-chain removal takes place in the mitochondria of steroidogenic tissues. Removal involves the hydroxylation of two adjacent car bons in the side chain (C-20 and C-22) followed by cleavage of the bond between them (Fig. 21–47). Formation of the various hormones also involves the intro duction of oxygen atoms. All the hydroxylation and oxygenation reactions in steroid biosynthesis are catalyzed by mixed-function oxidases (Box 21–1) that use NADPH, O2, and mitochondrial cytochrome P-450.
FIGURE 21–46 Some steroid hormones derived from cholesterol. The structures of some of these compounds are shown in Figure 10–19.
FIGURE 21–47 Side-chain cleavage in the synthesis of steroid hormones. Cytochrome P-450 acts as electron carrier in this mixed function oxidase system that oxidizes adjacent carbons. The process also requires the electron-transferring proteins adrenodoxin and adrenodoxin reductase. This system for cleaving side chains is found in mitochondria of the adrenal cortex, where active steroid pro duction occurs. Pregnenolone is the precursor of all other steroid hormones (see Fig. 21–46).
