Regulation of vertebrate liver HMG-CoA reductase via reversible modulation of its catalytic activity.
We have investigated the comparative biochemistry of in vitro regulation of HMG-CoA reductase (EC 1.1.1.34) in microsomal preparations from the livers of nine vertebrates. In all instances, reductase activity was rapidly and profoundly decreased by addition of MgATP. Reductase activities were restored to near or above initial levels after removal of MgATP and incubation with a crude, low molecular weight phosphatase preparation from rat liver cytosol. Restoration of reductase activity was inhibited both by NaF and by pyrophosphate, known inhibitors of phosphoprotein phosphatase activity. Liver cytosol of species other than the rat exhibits reductase phosphatase activity. The converter enzymes that catalyze modulation of MG-CoA reductase activity (reductase kinase and reductase phosphatase) thus appear to be ubiquitous in vertebrate liver. Interconversion in vitro of active and inactive forms of reductase probably is general for vertebrate liver also. The majority of the reductase present in vertebrate liver may be present in a catalytically inactive or latent form in vivo. Under the experimental conditions used, the fraction present in the active form is, for a given species, quite constant. Species to species, from 20-45% of the reductase appears to be present in the active form.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001001:Anura; D002645:Chickens; D006224:Cricetinae; D011756:Diphosphates / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D005399:Fishes; D005849:Gerbillinae; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D010749:Phosphoprotein Phosphatases / Q000494:pharmacology; D011817:Rabbits; D011892:Rana catesbeiana; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology; D013552:Swine
D011756:Diphosphates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000255:Adenosine Triphosphate; D012969:Sodium Fluoride; D006903:Hydroxymethylglutaryl CoA Reductases; C024938:HMG-CoA reductase phosphatase; D010749:Phosphoprotein Phosphatases; D008274:Magnesium