Mechanism of activation of liver acetyl-CoA carboxylase by cell swelling.
(1993) European journal of biochemistry / FEBS — Vol. 217, n° 3, p. 1083-1089 (1993)
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- The activation of hepatic glycogen synthase by the amino-acid-induced cell swelling has been attributed to the stimulation of [glycogen-synthase]-phosphatase resulting from an increase in the intracellular content in glutamate and aspartate, and a decrease in intracellular Cl-, which is a compensatory response to cell swelling [Meijer, A. J., Baquet, A., Gustafson, L., van Woerkom, G. M. & Hue, L. (1992) J. Biol. Chem. 267, 5823-5828]. Here we studied whether the activation of acetyl-CoA carboxylase by cell swelling could be explained by the same mechanism. The activation of endogenous or purified acetyl-CoA carboxylase was measured in gel-filtered liver extracts or cytosols. No activation could be observed under basal conditions but a fivefold stimulation was obtained with concentrations of glutamate (20-25 mM) found in hepatocytes incubated with glutamine. A similar stimulation was also observed with other dicarboxylic acids such as malonate and succinate, or with metal ions like Mg2+, Ca2+ and Mn2+ (10 mM). The addition of 50-100 mM Cl- was found to inhibit the activation of acetyl-CoA carboxylase by some 20-30%. Mg2+ was also found to stimulate the activation of the endogenous glycogen synthase. The glutamate-stimulated and Mg(2+)-stimulated activation of glycogen synthase and acetyl-CoA carboxylase was unaffected by 10 microM inhibitor-2, a specific inhibitory protein of protein phosphatase-1, but could be nearly completely blocked by the phosphatase inhibitor microcystin-LR. Our data suggest that the amino-acid-induced activation of acetyl-CoA carboxylase and glycogen synthase in the liver occurs by a common ionic mechanism.
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Baquet, A., Gaussin, V., Bollen, M., Stalmans, W., & Hue, L. (1993). Mechanism of activation of liver acetyl-CoA carboxylase by cell swelling. European journal of biochemistry / FEBS, 217(3), 1083-1089. https://doi.org/10.1111/j.1432-1033.1993.tb18340.x (Original work published 1993)