DISSOCIATION OF BETA-HYDROXY-BETA-METHYLGLUTARYL-COA REDUCTASE-ACTIVITY FROM OVERALL RATE OF CHOLESTEROL-SYNTHESIS IN LIVER FOLLOWING INTRAVENOUS ADMINISTRATION OF LIPID

  • 1 January 1976
    • journal article
    • research article
    • Vol. 251  (12) , 3831-3833
Abstract
After i.v. administration of triglyceride carried in either intestinal lipoproteins or in an artificial fat emulsion to the intact rat, the enzymatic activities of in vitro liver microsomal .beta.-hydroxy-.beta.-methylglutaryl-CoA reductase activity became markedly elevated. This elevation of enzyme activity was not associated with a corresponding change in the overall rate of cholesterol synthesis in the rat liver slice as measured by the incorporation of either [3H]water or [1-14C]octanoate into nonsaponifiable lipids or into digitonin-precipitable sterols. The degree of dissociation of hydroxymethylglutaryl-CoA reductase activity from the overall rate of cholesterol synthesis correlated with the amount of lipid administered to the animal, the level of circulating lipids and the level of ketone synthesis manifest in the liver cell suggesting that this phenomenon might be the consequence of a detergent effect of elevated cellular levels of fatty acids. In any event, under these experimental circumstances hydroxymethylglutaryl-CoA reductase activity no longer reflects the rate at which the liver cell is synthesizing cholesterol.