Isocaproic aldehyde

In the body, natural steroid hormones are synthesized from cholesterol. The rate-determining step is the oxidation of the cholesterol side chain, which forms pregnenolone and isocaproic aldehyde. 

Cholesterol is the biochemical precursor for both, the adrenocorticosteroid hormones cortexone and cortisol, and the sex hormones testosterone and oestradiol. Cholesterol is first hydroxylated at C-20 and C-22. The next tangible intermediate is pregnen-3)S-ol-20-one (Latin praegnatio pregnancy). After oxidation and a retro-acyloin reaction, the rest of the molecule is formally cleaved off as isocaproic aldehyde (4-methylpentanal). 

The P450 llAl reaction proceeds in a three-step sequence, with generation of 22R)-20a, 22-dihy-droxycholesterol as an intermediate (Fig. 9.22) [1935]. Oxidative cleavage of the diol to pregnenolone and 4-methylpentanal (isocaproic aldehyde) completes the overall reaction. The mechanism of the last step is not completely clear, but some proposals have been presented [1936-1938]. 

It has been proposed that the monohydroxylate is further hydroxylated to yield a dihydroxylate. A des-molase capable of attacking either 20- or 22-hydroxy derivatives yields, by splitting the side chain, pregnenolone and isocaproic aldehyde, which is converted to isocaproic acid. It may be significant that the carbon-to-carbon split that is catalyzed by desmolase is sensitive to ACTH, LSH, HCG, and angiotonin II (which... 

Side-chain Cleavage.—Doubt has been cast on the claim that in cholesterol (93) either C(20)—C(22) or C(17)—C(20) may be cleaved. Using [1,2-3H2,26- " C]-cholesterol, active isocaproic acid was obtained, but 6-methylheptan-2-one (94) was largely inactive and contained both tritium and The first-formed compound is probably the aldehyde (95), which is further metabolized to both isocaproic acid and 4-methylpentan-l-ol. ... 

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