17,20-Desmolase

Several en2yme defects will cause a deficiency of testosterone production during fetal development. These include 20a-hydroxylase (cholesterol 20,22-desmolase) deficiency, which prevents conversion of cholesterol to pregnenolone and results in congenital lipoid adrenal hyperplasia, so named because the adrenals are large and filled with lipoid... 

Figure 2 Biosynthesis of steroid hormones. Abbreviations of names of enzymes 20, 22-Des, 20,22-desmolase 17,20-Des, 17,20-desmolase 3 3-HSD, 3 3-hydroxysteroid-dehydrogenase 17 3-HSD, 17 3-hydroxysteroid-dehydrogenase 18-HSD, 18-hydroxyste-roid-dehydrogenase 17a-OH, 17a-hydroxylase 21-OH, 21-hydroxylase ll 3-OH, 11 3-hydroxylase 18-OH, 18-hydroxylase.

Steroid hormones are crucial signal molecules in mammals. (The details of their physiological effects are described in Chapter 34.) Their biosynthesis begins with the desmolase reaction, which converts cholesterol to preg-... 

Aminoglutethimide (Cytadren) is a competitive inhibitor of desmolase, the enzyme that catalyzes the conversion of cholesterol to pregnenolone it also inhibits 11-hydroxylase activity. This drug also reduces estrogen production by inhibiting the aromatase enzyme complex in peripheral (skin, muscle, fat) and steroid target tissues. 

Fig. 3. Gonadal steroid biosynthetic pathway and the catalytic enzymes 1) cytochrome P-450scc 2) -hydroxysteroid dehydrogenase 3) 17a-hydroxylase (P-450scc17) 4) 17,20-desmolase or 17,20-lyase 5) 17(3-hydroxysteroid dehydrogenase 6) 5a-reductase and 7) P-450 aromatase.

The initial reaction in steroid hormone biosynthesis is catalyzed by desmolase (side-chain cleavage complex), which is found in the mitochondria of steroid-producing tissues (e.g., adrenals, gonads). The reaction is shown in figure 20.22. The product, pregnenolone, is subsequently transferred to the endoplasmic reticulum, where an oxidation of... 

Figure 16.4 Biosynthesis of various classes of steroid hormones. Reaction (A) is catalyzed by a cholesterol desmolase, which oxidizes the cholesterol side chain. Reactions (D) are catalyzed by 21-hydroxylases, which are defective in congenital adrenal hyperplasia. (Reproduced by permission from Schwarz V. A Clinical Companion to Biochemical Studies. Reading Freeman, 1978, p. 94.)...

CHOLESTEROL DESMOLASE (CYP11A) I.. 17a-HYDR0XYLASE (CYP17) 17,20-LYASE... 

G-12) Cholesterol desmolase. A partial block at this control step reduces the levels of all the steroid hormones. 

Steroid hormones contain 21 or fewer carbon atoms, whereas cholesterol contains 27. Thus, the first stage in the synthesis of steroid hormones is the removal of a six-carbon unit from the side chain of cholesterol to form pregnenolone. The side chain of cholesterol is hydroxylated at C-20 and then at C-22, and the bond between these carbon atoms is subsequently cleaved by desmolase. Three molecules of NADPH and three molecules of O2 are consumed in this remarkable six-electron oxidation. 

Cholesterol side-chain cleavage (SCC, desmolase) 17(X-Hydroxylase/17,20 lyase 2THydroxyIasc p-Hydroxylase... 

Enzymes can be divided into two main groups, the hydrolases and desmolases. The desmolases regulate the various oxidation-reduction processes. The desmo-lase which is present in blood and interacts with hydrogen peroxide is called catalase it decomposes H2O2 into water and oxygen ... 

The conversion of indole to tryptophan has been much more extensively studied. This is brought about by direct reaction of indole and serine under the influence of the enzyme tryptophan desmolase (better named tryptophan synthetase) (302, 853, 854) which requires p5U-idoxal phosphate as a coenzyme (890). The enzyme has been obtained in the cell-free state (890) and partially purified (965) and its genetics in Neurospora studied in detail (966). Zinc appears to play some part in tryptophan desmolase formation or function (628). 

Gonadotropin and gonadotropin-receptor abnormalities signal defects Enzyme deficiencies cho/esfero/c/esmo/ase, 17a-hydroxylase, 17, 20-desmolase Galactosemia... 

Key to reactions (enzymes) 0, via mevalonate, isopentenyl phosphate, squalene 1, hydroxylase, desmolase (20,22) S, A -3j8-hydroxysteroid dehydrogenase, 5(4)-isomerase S, 21-hydroxylase 4, 17a-hydroxylase 6, ll 3-hydroxylase 6, desmolase (17,20) 7, 17 -hydroxysteroid dehydrogenase 8, 19-hydroxylase 9, aromatization. 

Cholesterol desmolase No information on steroids in urine (cholesterol accumulates in adrenal glands) Low Low... 

This can be due to defects in several enzyme systems required for the formation of cortisol (Fig. 8), but in all cases the inadequate level of cortisol in the blood causes corticotropin to be secreted by the pituitary in increasing amount this in turn causes hyperplasia of the adrenal glands with overproduction of those steroids not affected by the enzyme block. The most common deficiency is in 21-hydroxylase, but deficiencies have also been reported in infants and children of 3j8-HSD, lljff-hydroxy-lase, and cholesterol desmolase, and in older infants of 17a-hydroxylase (N4). 

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