Creatine metabolism in skeletal muscle. I. Creatine movement across muscle membranes.

In studies in vitro, creatine-114 C entered the extensor digitorum longus of young rats by a saturable process which had an apparent Vmax of 0.6 mmole per liter of intracellular water per hour and an apparent Km of 5 X 10 4 M. Creatine entry by nonsaturable processes was negligible at physiologic external creatine concentrations. Anaerobiosis, 1 X 103 M 2,4-dinitrophenol, and cooling each reduced the intracellular accumulation of creatine-'4 C. The apparent Q10 for entry was 2.7. Loss of creatine from the muscle accelerated rapidly during incubation at 370 and exceeded the rate of creatine entry, but no connection between entry and loss was apparent. The large creatine loss in vitro was considered to be an artifact because it accelerated so rapidly during incubation and because it is inconsistent with observations from earlier experiments in vivo which indicate that much of the creatine in skeletal muscle is trapped there. A special mechanism for entry, the saturable process, and intracellular trapping of creatine provide a plausible explanation for the high creatine content of skeletal muscle.