Uptake and phosphorylation of (14C) creatine by mouse cardiac muscle in vivo

Tracer doses of [1-14C]creatine were given intravenously to mice and the total activity of cardiac muscle compared with skeletal muscle and diaphragm were determine periodically thereafter for up to 5 days. An inverse relationship was found between the rate of uptake, i.e., turnover of creatine in vivo and total muscular creatine, cardiac muscle exhibiting the most active turnover of all muscles. Similarily, the in vivo labeling of intracellular creatine phosphate of cardiac muscle proceeded at a rate much faster than in skeletal muscle. Hypoxia (10 percent O2--90 percent N2) during the equilibration of the pulse label inhibited both the uptake of creatine and its intracellular phosphorylation. We suggest that the rapid metabolism of creatine is related to the predominance of mitochondrial oxidation in cardiac muscle, creatine serving as a carrier of high energy phosphate groups from mitochondria to myofibrillar ATP and reflecting a directed intracellular energy flux.