ACTIVATION OF HEPATIC ACETYL-COA CARBOXYLASE BY GLUTAMATE AND MG2-2A(IS MEDIATED BY PROTEIN PHOSPHATASE)

The activation of hepatic acetyl-CoA carboxylase by Na+-cotransported amino acids such as glutamine has been attributed mainly to the stimul ation of its dephosphorylation by accumulating dicarboxylic acids, e.g . glutamate. We report here on a hepatic species of protein phosphatas e-2a that activates acetyl-CoA carboxylase in the presence of physiolo gical concentrations of glutamate or Mg2+ and, under these conditions, accounts for virtually all the hepatic acetyl-CoA carboxylase phospha tase activity. Glutamate also stimulated the dephosphorylation of a sy nthetic pentadecapeptide encompassing the Ser-79 phosphorylation site of rat acetyl-CoA carboxylase, but did not affect the dephosphorylatio n of other substrates such as phosphorylase. Conversely, protamine, wh ich stimulated the dephosphorylation of phosphorylase, inhibited the a ctivation of acetyl-CoA carboxylase. A comparison with various species of muscle protein phosphatase-2A showed that the stimulatory effects of glutamate and Mg2+ on the acetyl-CoA carboxylase phosphatase activi ty are largely mediated by the regulatory A subunit. Glutamate and Mg2 + emerge from our study as novel regulators of protein phosphatase-2A when acting on acetyl-CoA carboxylase.