Gaussin V, Hue L, Stalmans W, Bollen M
Hormone and Metabolic Research Unit, University of Louvain Medical School, Brussels, Belgium.
Biochem J. 1996 May 15;316 ( Pt 1)(Pt 1):217-24. doi: 10.1042/bj3160217.
The activation of hepatic acetyl-CoA carboxylase by Na(+)-cotransported amino acids such as glutamine has been attributed mainly to the stimulation of its dephosphorylation by accumulating dicarboxylic acids, e.g. glutamate. We report here on a hepatic species of protein phosphatase-2A that activates acetyl-CoA carboxylase in the presence of physiological concentrations of glutamate or Mg2+ and, under these conditions, accounts for virtually all the hepatic acetyl-CoA carboxylase phosphatase activity. Glutamate also stimulated the dephosphorylation of a synthetic pentadecapeptide encompassing the Ser-79 phosphorylation site of rat acetyl-CoA carboxylase, but did not affect the dephosphorylation of other substrates such as phosphorylase. Conversely, protamine, which stimulated the dephosphorylation of phosphorylase, inhibited the activation 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 activity 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.
谷氨酰胺等通过钠共转运的氨基酸对肝脏乙酰辅酶A羧化酶的激活作用，主要归因于积累的二羧酸（如谷氨酸）对其去磷酸化的刺激。我们在此报告一种肝脏中的蛋白磷酸酶2A，它在生理浓度的谷氨酸或镁离子存在下激活乙酰辅酶A羧化酶，并且在这些条件下，几乎占了肝脏中所有乙酰辅酶A羧化酶磷酸酶活性。谷氨酸还刺激了包含大鼠乙酰辅酶A羧化酶丝氨酸79磷酸化位点的合成十五肽的去磷酸化，但不影响其他底物（如磷酸化酶）的去磷酸化。相反，刺激磷酸化酶去磷酸化的鱼精蛋白抑制了乙酰辅酶A羧化酶的激活。与各种肌肉蛋白磷酸酶2A的比较表明，谷氨酸和镁离子对乙酰辅酶A羧化酶磷酸酶活性的刺激作用主要由调节性A亚基介导。在作用于乙酰辅酶A羧化酶时，谷氨酸和镁离子作为蛋白磷酸酶2A的新型调节剂出现在我们的研究中。
