The influence of the side chain on sterol side-chain cleavage in rat adrenal glands

Abstract

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 Ca 2+, rat adrenocortical mitochondria converted the analogue with two less methylene groups (C 25) than cholesterol into pregnenolone at a faster rate than cholesterol. The analogues with one or three less methylene groups ( 26 or C 24) 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 C 24 and C 25 analogues were converted into pregnenolone much more efficiently than was cholesterol or the C 26 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.