Inactivation of rat liver HMG-CoA reductase phosphatases by nucleotides.
Incubation of four purified rat liver HMG-CoA reductase phosphatases, with ATP, ADP and AMP caused a concentration-dependent inactivation of enzyme activities. The nucleotides of guanine, cytosine and uracil produced similar effects to those by the nucleotides of adenine for the same number of phosphates present in the molecules. The greater the number of phosphate groups in nucleotides, the higher was the inhibition in reductase phosphatases observed. Preincubation of phosphatases with ATP and subsequent dilution did not diminish the inactivation effect, showing that nucleotides inhibit the enzyme prior to their binding to the substrate. A relationship was observed between those concentrations of nucleotides which produce 50% inactivation and the logarithm stability constant of Mg or Mn salts of nucleotides. ATP-inactivated enzymes were reactivated by Mn++ and to a lesser proportion by Mg++, the conclusion being that HMG-CoA reductase phosphatases have the characteristics of metalloenzymes.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D009711:Nucleotides / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D051381:Rats
D009711:Nucleotides; D008345:Manganese; D000255:Adenosine Triphosphate; C024938:HMG-CoA reductase phosphatase; D010749:Phosphoprotein Phosphatases; D008274:Magnesium