Regulation of rat liver glycogen synthetase. Carboxylic acid activation of liver glycogen synthetase.

Rat liver glycogen synthetase is strongly stimulated by cellular carboxylic acids which are intermediates of glycolysis and the tricarboxylic acid cycle. Activation of glycogen synthetase by the carboxylic acids may coordinate hepatic glycogen deposition with the functional status of the tricarboxylic acid cycle. At physiological concentrations of the carboxylic acids, the I form is preferentially stimulated. Whereas citrate, isocitrate, succinate, etc., stimulate total glycogen synthetase activity about 25 to SO%, these compounds stimulate the I activity 6to 8-fold. Citrate was used as a model compound in studies of the mechanism of glycogen synthetase activation. Stimulation of the enzyme is the result of modification of the glucose-6-P binding site which accompanies a conformational change mediated by citrate.