title: Rapid modulation of rat hepatocyte HMG-CoA reductase activity by cyclic AMP or cyclic GMP.
abstract: Rat hepatocytes were used to demonstrate rapid, transient effects on the modulation state (defined as the fraction of the enzyme present in the catalytically active form) of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase, E.C. 1.1.1.34). Insulin elevated, while glucagon, cAMP or cGMP lowered HMG-CoA reductase modulation state within 10 to 15 min. These changes were accompanied by a parallel change in sterol synthesis. Total HMG-CoA reductase activity was not altered. Rapid modulation of HMG-CoA reductase activity therefore constitutes a viable in vivo control mechanism. By contrast to the hormones and second messengers, mevalonolactone lowered both HMG-CoA reductase modulation state and total reductase quantity.
authors.forename: R
authors.initials: R
authors.lastname: Henneberg
authors.forename: V W
authors.initials: VW
authors.lastname: Rodwell
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007328:Insulin; D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine; C015367:mevalonolactone; D005934:Glucagon; D000242:Cyclic AMP; D006903:Hydroxymethylglutaryl CoA Reductases; D006152:Cyclic GMP; D008798:Mevalonic Acid