Effect of mercaptopicolinic acid and of transaminase inhibitors on glycogen synthesis by rat hepatocytes.

To explore the mechanism of the stimulation of glycogen synthesis by amino acids (1) we have studied the effects of transaminase inhibitors and of mercaptopicolinic acid, (MPA) an inhibitor of phosphoenol pyruvate carboxykinase. Mercaptopicolinic acid enhanced glycogen synthesis from fructose, dihydroxyacetone and xylitol. Stimulation of glycogen synthesis with hepatocytes from fasted rats by 0.5 mM mercaptopicolinic acid was 50–70% as effective as 10 mM glutamine. With hepatocytes from fed rats, the stimulation of glycogen synthesis by mercaptopicolinic acid was more pronounced, and stimulation by mercaptopicolinic acid and amino acids was additive. Glycogen synthesis as high as 1% in wet weight per hour was attained in hepatocytes with a high initial glycogen content. Over 80% of glycogen synthase was in the active (a) form. Amino oxyacetic acid greatly depressed or abolished the stimulatory effect of glutamine and asparagine and of mercatopicolinic acid, and induced extensive glycogen breakdown in hepatocytes of fed rats.