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.
D000085:Acetates / Q000378:metabolism; D000090:Acetoacetates / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D005977:Glutarates / Q000494:pharmacology*; D006880:Hydroxy Acids / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008297:Male; D008798:Mevalonic Acid / Q000096:biosynthesis*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D000085:Acetates; D000090:Acetoacetates; D005977:Glutarates; D006880:Hydroxy Acids; D000429:Alcohol Oxidoreductases; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid