Inactivation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in vitro. An adenine nucleotide-dependent reaction catalyzed by a factor in human fibroblasts.
Microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase prepared from either rat liver or human fibroblasts was shown to be inactivated in vitro by a factor in extracts of cultured human fibroblasts in a reaction requiring ATP or ADP and Mg2+ or Mn2+. The inactivation factor was found in the soluble fraction of fibroblasts extracts and was shown to be heat-labile, nondialyzable, and precipitable with ammonium sulfate. The inactivation reaction was prevented by the addition of either an ATP-regenerating system or an ADP-regenerating system, suggesting that the presence of both adenine nucleotides may be required. A series of kinetic experiments suggested that the fibroblast inactivation factor catalyzes the conversion of the microsomal enzyme from an active to an inactive form. The finding that solubilized preparations of 3-hydroxy-3-methylglutaryl coenzyme A reductase from both rat liver and human fibroblasts were resistant to inactivation raises the possibility that some unidentified microsomal component also may participate in the inactivation reaction.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004355:Drug Stability; D004492:Edetic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000201:enzymology*; D005615:Freezing; D005977:Glutarates; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology; D011506:Proteins / Q000502:physiology; D051381:Rats; D012867:Skin; D013997:Time Factors
D005977:Glutarates; D011506:Proteins; D008345:Manganese; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D004492:Edetic Acid; D000429:Alcohol Oxidoreductases; D008274:Magnesium