BIOCHEMISTRY - L. Stryer - 1984

VOLUME 2

PART III. BIOSYNTHESIS OF MACROMOLECULE PRECURSORS

CHAPTER 20. BIOSYNTHESIS OF MEMBRANE LIPIDS AND STEROID HORMONES

20.22. Pregnenolone Is Formed from Cholesterol by Side-Chain Cleavage

Steroid Hormones contain no more than 21 carbon atoms, whereas Cholesterol contains 27. The First stage in the synthesis of steroid hormones is the removal of the six-carbon fragment from the cholesterol side chain, yielding pregnenolone. The side chain of cholesterol is hydroxylated at carbon atoms C-20 and C-22, after which the bond between these atoms is cleaved. The final reaction is catalyzed by desmolase. All three reactions proceed with the participation of NADPH and O₂.

Adrenocorticotropic hormone (ACTH, or corticotropin) is a polypeptide synthesized in the anterior Pituitary Gland. ACTH stimulates The conversion of cholesterol into pregnenolone, the precursor of all steroid hormones.

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20.23. Synthesis of Progesterone and Corticoids

Progesterone is synthesized from pregnenolone in two steps. The 3-hydroxy group of pregnenolone is oxidized to a 3-oxo group, and the ∆⁵ double bond is isomerized to a ∆⁴ double bond. Cortisol, the principal glucocorticoid, is synthesized from progesterone by the hydroxylation of carbon atoms C-17, C-21, and C-11; C-17 must be hydroxylated before C-21, whereas C-11 hydroxylation can occur at any stage. The Enzymes catalyzing these reactions are highly specific, as demonstrated by certain Inherited Disorders of steroid METABOLISM. The initial step in the synthesis of aldosterone, the major mineralocorticoid, is the hydroxylation of progesterone at C-21. The resulting deoxycorticosterone is then hydroxylated at C-11. Subsequently, the C-18 angular methyl group is oxidized to an aldehyde group, yielding aldosterone.

20.24. Synthesis of Androgens and Estrogens

The synthesis of androgens (Fig. 20.21) begins with the hydroxylation of progesterone at C-17. Next, the side chain comprising C-20 and C-21 is cleaved off, yielding the androgen androstenedione. Another androgen, testosterone, is formed by the reduction of the 17-oxo group of androstenedione. Androgens contain 19 carbon atoms. Estrogens are synthesized from androgens by the removal of the C-19 angular methyl group and The formation of an aromatic ring A. These reactions proceed with the participation of NADPH and O₂. The estrogen estrone is derived from androstenedione, whereas another estrogen, estradiol, is formed from testosterone.

Fig. 20.20. Synthesis of progesterone and corticosteroids

Fig. 20.21. Synthesis of androgens and estrogens