Inactivation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in vitro. An adenine nucleotide-dependent reaction catalyzed by a factor in human fibroblasts

Abstract

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.