Isoproterenol and insulin control the cellular localization of ATP citrate-lyase through its phosphorylation in adipocytes.
The enzyme ATP citrate-lyase of the fatty acid synthesis pathway is phosphorylated in vitro and in isolated cells. However, no effect of phosphorylation on the enzyme activity has been detected. It is demonstrated that the beta-adrenergic agonist isoproterenol or insulin both promote an immobilization of ATP citrate-lyase, detected in digitonin-permeabilized adipocytes. This effect was reproduced by the cyclic AMP analog cyclic 8-bromo-AMP. The beta-adrenergic antagonist propranolol blocked, but failed to reverse, the isoproterenol-directed effect. Propranolol also failed to reverse the isoproterenol-induced increased phosphorylation of ATP citrate-lyase specifically. In response to increasing concentrations of isoproterenol, an increased extent of phosphorylation of ATP citrate-lyase was paralleled by an increased immobilization of the enzyme. It is suggested that the state of phosphorylation of ATP citrate-lyase in adipocytes controls the localization in the cell.
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects* / Q000201:enzymology; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D004072:Digitonin / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D010766:Phosphorylation; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011433:Propranolol; D001275:ATP Citrate (pro-S)-Lyase; D004072:Digitonin; D007545:Isoproterenol