Glycogenesis from lactate in rabbit skeletal muscle fiber types.
The path of glycogen synthesis from three-carbon precursors was studied via single-pass perfusions in three distinct rabbit skeletal muscle preparations, i.e., glycolytic (greater than 99% type IIb), oxidative (greater than 97% type I), and mixed (type I, IIa, and IIb). The extent of interaction between the Krebs cycle and glycogenesis was assessed utilizing [1-14C]- or [2-14C]lactate at basal (1.1 +/- 0.1 mM) and elevated (8.1 +/- 0.3 mM) lactate concentrations (protocols 1 and 2). Under conditions in which the net balance of glucose and lactate, [14C]lactate removal, and venous lactate-specific activity were similar, the yields of 14CO2 and [14C]glycogen were not significantly influenced by position of the label. Additional perfusions were performed with lactate (8.0 +/- 0.1 mM) and acetate (1.0 +/- 0.1 mM) as sole substrates and either [U-14C]lactate or [2-14C]acetate as the tracer. Under conditions of net glycogen synthesis, the incorporation of [14C]lactate into glycogen [in disintegrations/min (dpm).g-1.2 h-1] was 40,940 +/- 3,320, 1,540 +/- 320, and 32,600 +/- 4,100 in the glycolytic, oxidative, and mixed preparations, respectively. However, no incorporation of [2-14C]acetate into glycogen was observed in any preparation, despite a significant yield of 14CO2. Mercaptopicolinic acid, a potent inhibitor of phosphoenolpyruvate carboxykinase (PEPCK), demonstrated no significant effect on net substrate balance, tracer uptake, net glycogen synthesis, incorporation of [14C]lactate and [3H]-glucose into glycogen, or 14CO2 yield. Current results suggest an extramitochondrial route for net glycogen synthesis from three-carbon precursors, exclusive of PEPCK, that is consistent across all mammalian skeletal muscle fiber types.
Pagliassotti
M J
MJ
Department of Exercise Science, University of Southern California, Los Angeles 90089.
Donovan
C M
CM
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D006003:Glycogen / Q000096:biosynthesis*; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010477:Perfusion; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors; D010848:Picolinic Acids / Q000494:pharmacology; D011817:Rabbits
D000085:Acetates; D007773:Lactates; D010848:Picolinic Acids; D019344:Lactic Acid; C008363:3-mercaptopicolinic acid; D006003:Glycogen; D010729:Phosphoenolpyruvate Carboxykinase (GTP)