Creatine and glycocyamine metabolism in rabbits in vitamin E deficiency.

As is well known, many animals, when deprived of vitamin E (cr-tocopherol), develop a paralysis of the voluntary muscles (1). The partly grown rabbit becomes completely helpless in 3 to 4 weeks. The progress of the disease is characterized by histological changes and alterations in chemical composition. Thus muscle creatine declines considerably (2), in rats even before any abnormality in structure is evident (3). There is a marked increase in urinary creatine (4), which may ultimately be 5ts much w 30-fold the usual excretion (5). Since muscle loses little more than half its normal creatine content, the rate of creatine synthesis must be increased. According to presently accepted views, the kidney is responsible for the initial synthesis of glycocyamine from glycine and arginine, and, in most species examined, the subsequent methylation of this compound is confined to the liver (6, 7). If the synthesis of creatine is accelerated, one might expect to find a higher content of creatine in the liver of dystrophic animals. In preliminary experiments (8), this was found to be true. If glycocyamine is necessarily also synthesized in larger amounts, its concentration in the kidney might be elevated, together with a rise in the blood. If the rate of methylation in the liver were equally increased, the level of glycocyamine might remain unchanged. The source of the component units of creatine, especially in the later stages of dystrophy, is probably muscle protein; in the early stages, while the animals are still gaining weight, the origin of the extra creatine is not immediately obvious. When the animals can no longer eat, the creatinuria of dystrophy is compounded with that of inanition. The excretion of creatinine in nutritional muscular dystrophy appears to be relatively unchanged (4). The view that urinary creatinine has its origin primarily in the creatine phosphate of muscle (9) cannot be reconciled with the observed diminution of creatine phosphate in dystrophic