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  • Title: Mode of action of the lipid-lowering agents, clofibrate and BM 15075, on cholesterol biosynthesis in rat liver.
    Author: Berndt J, Gaumert R, Still J.
    Journal: Atherosclerosis; 1978 Jun; 30(2):147-52. PubMed ID: 678316.
    Abstract:
    When rats were fed a diet containing 0.3% clofibrate or a derivative of this drug, BM 15075, serum cholesterol was lowered within 3-7 days by 26-38%. Both drugs diminished the activity of hydroxymethylglutaryl CoA reductase, the regulatory enzyme of hepatic cholesterol biosynthesis, in rat liver microsomes by about 60% under the same conditions. The decrease in the activity of the enzyme obviously is due to changes in the amount of enzyme protein. Under in vitro conditions microsomal hydroxymethylglutaryl CoA reductase was inhibited competitively by (1.35 mM) clofibric acid (sodium salt) and by BM 15075 (1 mM) with respect to its substrate. These results give evidence that these drugs can affect both, the rate of synthesis and the substrate affinity of hydroxymethylglutaryl CoA reductase.
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