The influence of the side chain on sterol side-chain cleavage in rat adrenal glands.
The cholesterol side-chain cleavage enzyme system of rat adrenal cortex, the enzyme catalyzing a rate-limiting step of adrenal steroidogenesis, was shown to metabolize a series of cholesterol analogues to pregnenolone. In the presence of Ca2+, rat adrenocortical mitochondria converted the analogue with two less methylene groups (C25) than cholesterol into pregnenolone at a faster rate than cholesterol. The analogues with one or three less methylene groups (C26 or C24) were metabolized at a similar rate to cholesterol. Lengthening the non-polar side chain produced analogues that did not appear to be metabolized. Studies of the metabolism of these analogues in isolated rat adrenocortical carcinoma cells showed that the C24 and C25 analogues were converted into pregnenolone much more efficiently than was cholesterol or the C26 sterol. The experimental findings are explained in terms of the differing ability of each exogenously added sterol to gain access to the active site of the sterol side-chain cleavage enzyme by passage through the membranes of the adrenal cell.
D000311:Adrenal Glands / Q000201:enzymology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism*; D005260:Female; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D011284:Pregnenolone / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D011284:Pregnenolone; D010088:Oxidoreductases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D002118:Calcium