title: Mechanism of glucagon inhibition of liver acetyl-CoA carboxylase. Interrelationship of the effects of phosphorylation, polymer-protomer transition, and citrate on enzyme activity.
abstract: The short-term regulation of rat liver acetyl-CoA carboxylase by glucagon has been studied in hepatocytes from rats that had been fasted and refed a fat-free diet. Glucagon inhibition of the activity of this enzyme can be accounted for by a direct correlation between phosphorylation, polymer-protomer ratio, and activity. Glucagon rapidly inactivates acetyl-CoA carboxylase with an accompanying 4-fold increase in the phosphorylation of the enzyme and 3-fold increase in the protomer-polymer ratio of enzyme protein. Citrate, an allosteric activator of acetyl-CoA carboxylase required for enzyme activity, has no effect on these phenomena, indicating a mechanism that is independent of citrate concentration within the cell. The observation of these effects of glucagon on acetyl-CoA carboxylase activity is absolutely dependent upon the minimization of proteolytic degradation of the enzyme after cell lysis. Therefore, for the first time, an interrelationship has been demonstrated between phosphorylation, protomer-polymer ratio, and citrate for the inactivation of acetyl-CoA carboxylase by glucagon.
authors.forename: T L
authors.initials: TL
authors.lastname: Swenson
authors.forename: J W
authors.initials: JW
authors.lastname: Porter
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D002499:Centrifugation, Density Gradient; D002951:Citrates / Q000378:metabolism*; D019343:Citric Acid; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D005934:Glucagon / Q000494:pharmacology*; D008025:Ligases / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010766:Phosphorylation; D011108:Polymers / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D002951:Citrates; D011108:Polymers; D019343:Citric Acid; D005934:Glucagon; D008025:Ligases; D000103:Acetyl-CoA Carboxylase