Synthesis of Creatine in X-irradiated Rats

Summary

Synthesis and excretion of creatine and creatinine in total-body x-irradiated (600 r) rats has been investigated. Irradiated rats exhibited a marked creatinuria (486·0 per cent), whereas creatinine excretion was only slightly increased (17·1 per cent) as compared with that of non-irradiated control animals. The increased creatine excretion after irradiation has been ascribed to accelerated synthesis in the liver and to greater release from the muscle. In vitro studies on the synthesis of creatine in liver homogenates revealed that the synthetic activity decreased immediately after irradiation, but at later intervals showed a marked rise. The immediate fall in the creatine synthesis was not due to decreased availability of ATP or glutathione. Administration of nicotinamide to animals, to inhibit the new creatine synthesis in the liver, indicated that though the creatine formation in the liver of x-irradiated rats was elevated, it could not account for more than a small fraction (19·8 per cent) of the creatinuria observed. Most of the urinary creatine originated from the muscle, probably because of the impaired reconversion of creatine to phosphocreatine. Since the muscle ATP-creatine transphosphorylase activity was not affected by irradiation, it is suggested that the mobilization of muscle creatine to cause creatinuria is probably due to the diminution of glycolysis in the muscle of irradiated animals.