A study of carbon dioxide fixation into glycogen by mammalian skeletal muscle.

After the administration of NaHC*03 to the intact animal, labeled carbon has been found in the glycogen of skeletal muscle (1, 2). The explanation of this result may be (a) that all the reactions in the pathway from carbon dioxide to glycogen take place in skeletal muscle itself, as has been found to occur in cardiac muscle (3). On the other hand, it is also possible (5) that the muscle cannot carry out one or more of the essential reactions involved in the introduction of CO2 carbon into glycogen, but that this tissue merely completes a sequence of reactions to which other tissues must contribute. For example, skeletal muscle may not carboxylate pyruvate to oxalacetate (4, 5), a reaction considered as probably necessary for bringing CO2 carbon into the pyruvate-glycogen precursor poo1.l If, for this or some other reason, CO2 fixation into glycogen does not occur completely within the muscle itself, a plausible interpretation of the finding of fixed CO2 in muscle glycogen in the intact animal is that COz is incorporated into liver glycogen and that blood sugar derived from such glycogen is secondarily deposited in skeletal muscle. The purpose of the present investigation was to attempt to evaluate the extent to which the general alternative (a) may have been operating. The possible occurrence of CO2 fixation into skeletal muscle glycogen was studied with the aid of heavy carbon (either as bicarbonate or CO,) in three types of preparations: the intact rat, the eviscerated rat, and the isolated perfused dog gastrocnemius. Both unstimulated and stimulated muscles were studied. In the former, a net increase in glycogen was produced by the administration of glucose and insulin.