Inactivation of hepatic acetyl-CoA carboxylase by catecholamine and its agonists through the alpha-adrenergic receptors.
The effects of adrenergic agonists on acetyl-CoA carboxylase and fatty acid synthesis were studied in isolated rat hepatocytes from mature rats (300 to 350 g). Norepinephrine and phenylephrine inactivate acetyl-CoA carboxylase activity and inhibit fatty acid synthesis. The effects of both norepinephrine and phenylephrine were blocked by the alpha-adrenergic receptor blockers, phentolamine and phenoxybenzamine, and unaffected by the beta-receptor blocker propranolol. This inactivation was not mimicked by the beta-agonist isoproterenol. The measurable increase in cyclic AMP levels caused by norepinephrine and phenylephrine was abolished by the alpha-antagonist phentolamine and diminished by the beta-antagonist propranolol. Calcium depletion potentiated the increase in cyclic AMP levels by phenylephrine but abolished the phenylephrine inactivation of the carboxylase. The inactivation of acetyl-CoA carboxylase by phenylephrine was correlated with an increase in the incorporation of [32P]phosphate into the enzyme. Thus, catecholamines and their agonists promote phosphorylation and inactivation of acetyl-CoA carboxylase through the alpha-adrenergic receptor, and the inactivation requires calcium.
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D007700:Kinetics; D008025:Ligases / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D010656:Phenylephrine; D011433:Propranolol; D000242:Cyclic AMP; D008025:Ligases; D000103:Acetyl-CoA Carboxylase; D002118:Calcium; D009638:Norepinephrine; D010646:Phentolamine