title: Inactivation of rat liver HMG-CoA reductase phosphatases by polycarboxylic acids.
abstract: Incubation of the four purified HMG-CoA reductase phosphatases with the sodium salts of eleven polycarboxylic acids at concentrations of 40 mM, inactivated the enzymes to different degrees depending on the structure of the carboxylic acids. Maleate, malonate, oxalate, citrate, and hydroxymethylglutarate produced full inactivation at the concentration tested. When the four phosphatases were incubated with these acids, a concentration-dependent inactivation was observed. Fumarate, the trans isomer of maleate, produced little inactivation of the four phosphatases. Mevalonate did not inactivate at all. A relationship between those concentrations of acid that produced a 50% inactivation and the logarithm of the stability constant of Mg2+ or Mn2+ salts of polycarboxylic acids was observed. When reductase phosphatases were incubated with mixtures of polycarboxylic sodium salts and Mg2+ or Mn2+, an increase in the molar ratio divalent cation/carboxylic acid determined an increase in the four reductase phosphatase activities. The inactivating effect of citrate was on the phosphatases (high and low forms) and not on the substrates (HMG-CoA reductase, phosphorylase, and glycogen synthase). Reactivation of the citrate-inactivated phosphatases by Mn2+ and Mg2+ depended on the phosphorylated substrates, Mn2+ being the better activator. It is concluded that HMG-CoA reductase phosphatases are metalloenzymes.
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000494:pharmacology*; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004793:Enzyme Reactivators; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D051381:Rats
chemical_list: D002264:Carboxylic Acids; D003998:Dicarboxylic Acids; D004793:Enzyme Reactivators; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008345:Manganese; D008274:Magnesium