Metabolism of hydroxy sterols by rat liver

Abstract

5 alpha-[16-3H]lanost-8-ene-3 beta,15 alpha-diol and 5 alpha-[16-3H]lanost-8-ene-3 beta,15 beta-diol were both extensively metabolised by rat liver enzymes in vitro. Quantitatively, the most important product in both cases was a more polar compound, tentatively identified as a 5 alpha-lanost-8-enetriol. In addition, 5 alpha-[16-3H]lanost-8-ene-3 beta,15 beta-diol gave rise to the corresponding 3 beta,15beta-diol diester, whilst with 5 alpha-[16-3H]lanost-8-ene-3 beta,15 alpha-diol only the 3 beta-hydroxyl group was esterified. The enzymes involved may normally be responsible for metabolising spontaneously produced non-enzymic oxidation products of dietary or cellular cholesterol. High concentrations of 5 alpha-[16-3H]lanost-8-ene-3 beta,15 beta-diol stimulated ester formation. With both substrates, carbon monoxide inhibited formation of the polar sterol metabolite but stimulated ester formation. Under all conditions, cholesterol was a relatively minor metabolic product of either of the 5 alpha-lanost-8-ene-3 beta,15-diols.