Effect in vitro of 3-hydroxy-3-methylglutaric acid on the synthesis of mevalonate and its precursors.

Addition of 3-hydroxy-3-methylglutaric acid (free HMG) to supernatant-microsomal preparation decreased the synthesis of acetoacetate, HMG-CoA and mevalonolactone by 12%, 33% and 75%, respectively, from [2-14C] acetate. Free HMG also inhibited the activity of HMG-CoA reductase in the microsomes. It is concluded that HMG, apart from inhibiting the activity of HMG-CoA reductase (the rate limiting enzyme in cholesterogenesis) also interferes with the enzymatic steps involved in the conversion of acetate to HMG-CoA.