Kinetic analysis of glycogen synthase and PDC in cirrhotic rat liver and skeletal muscle.

Glycogen synthase (GS) and pyruvate dehydrogenase complex (PDC) were kinetically analyzed in the liver and skeletal muscle of fasted and refed rats with thioacetamide-induced cirrhosis of the liver. In control rats, refeeding induced a 54% decrease in the A0.5 for glucose 6-phosphate (G-6-P) of hepatic GS (P < 0.001), reflecting allosteric activation of the enzyme. In skeletal muscle the A0.5 for G-6-P did not change after refeeding, whereas the activity ratio increased by 56% (P < 0.01), indicating a greater percentage of the active G-6-P-independent form of the enzyme. In cirrhotic rats, neither the A0.5 for G-6-P of liver GS nor the activity ratio of muscle GS was influenced by refeeding. Consequently, glycogen replenishment was significantly impaired both in the liver (2.56 +/- 0.2 vs. 5.11 +/- 0.4 g/100 g; P < 0.001) and skeletal muscle (0.45 +/- 0.01 vs. 0.52 +/- 0.02 g/100 g; P < 0.01). Refeeding increased the percentage of the active form of hepatic PDC both in control (+88%; P < 0.01) and cirrhotic rats (+91%; P < 0.001). In the latter, however, the rates of total and active PDC were significantly lower than in controls [-44% and -40% in fasted (P < 0.005) and refed (P < 0.005) rats, respectively]. Muscle PDC kinetics (both maximal velocity and Michaelis constant) and the percent active form were identical in cirrhotic and control rats, regardless of the nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)