Desmolase, reaction catalyzed

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.)...

Tryptophan Degradation. Tryptophan desmolase catalyzes an essentially irreversible reaction. The formation of indole from tryptophan is catalyzed by a very similar but quite distinct enzyme, tryptophanase. ... 

Siibstitution. A modification of the jS-elimination reaction may be substitution of a new group. This has been proposed as the mechanism of action of tryptophan desmolase, in which indole is substituted for the OH of serine. This reaction was found to proceed to a measurable extent in model reactions, in spite of the competing 8-elimination reactions of both serine and tryptophan and other side reactions of indole compounds. Additional substitution reactions of biological significance are the formation of cystathionine from homocysteine and serine and the formation of (Sf-methylcysteine from methyl mercaptan and serine. These reactions are catalyzed by enzymes that require pyridoxal phosphate as a cofactor. 

The enzyme which catalyzes the formation of tryptophan from indole and serine has been named tryptophan desmolase. A cell-free preparation has been obtained from Neurospora mycelium which catalyzes this reaction. Pyridoxal phosphate has been found to be a necessary cofactor. The enzyme has been partially purified by Yanofsky. He found the optimum activity to be at pH 7.8, and confirmed the necessity of pyridoxal phosphate as a coenzyme. Effective inhibitors are Co++, Zn++, CN, hydroxylamine, and tryptophan. 

The final step in the formation of tryptophan is the condensation of indole with serine (Fig. 15, reaction 4). This reaction was demonstrated by Tatum and Bonner ( S4) in Neurospora. The enzyme catalyzing this reaction has been prepared by a number of investigators 2S5-2S7). It was first named tryptophan desmolase 288), and the name indole-serine ligase has also been suggested 286). At present tr3rptophan synthetase is favored. 

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