Coy D. Fitch

Creatine Metabolism in Vitamin E Deficiency.

Summary 1) Normal and Vit. E-deficient rabbits were killed at varying time intervals after injection of glycine-1-C14. Concentration and specific activities of kidney glycocyamine, liver creatine, skeletal muscle creatine and heart creatine were determined. Vit. E deficiency led to an elevated concentration of liver creatine, to reduced concentration of skeletal muscle creatine and did not influence the concentration of kidney glycocyamine or heart creatine. 2. The turnover rate of liver creatine and skeletal muscle creatine was increased in Vit. E-deficient rabbits. The turnover rate of heart creatine was considerably greater than the turnover rate of skeletal muscle creatine and was unaffected by Vit. E deficiency. The results show that in Vit. E deficient rabbits, rate of creatine synthesis is increased and turnover rate of skeletal muscle creatine is increased.

Effect of Diet and Sex on Kidney Transamidinase Activity in the Rat.

Summary The in vitro kidney transamidinase activity of female rats supplied with a purified diet and of chow-fed male rats was found to be approximately 50% of that of male rats supplied with the purified diet. This accounts for much of the variability that has previously been found in normal kidney transamidinase activity. The female rats did not have a greater creatinuria than the comparable male rats, but the chow-fed male rats exhibited moderate creatinuria. Extra dietary glycine did not increase the transamidinase activity of the female or chow-fed rats. Also, glycine had no effect on urinary excretion of creatine by creatine-fed rats. These observations indicate that there are factors other than creatine which limit the activity of kidney transamidinase.

Metabolism of l-alpha-tocopherol by the vitamin E-deficient rabbit.

Summary Nutritional muscular dystrophy in the rabbit can be cured by l-alpha-tocopheryl acetate administered either orally or intravenously. Based on duration of survival after a single 50 mg oral dose the average estimated daily requirement was 2.0 mg per kg of body weight for 3 rabbits that received d-alpha-tocopheryl acetate and 9.5 for 2 rabbits that received l-alpha-tocopheryl acetate. After intravenous treatment with the same dose of these compounds, using 2 rabbits in each group, the estimated requirements were 1.2 and 8.0 for the d- and l-epimers, respectively. Liver and serum concentrations of tocopherol decreased more rapidly after treatment with l-alpha-tocopheryl acetate than after treatment with the same amounts of d-alpha-tocopheryl acetate. These observations suggest that the biological inferiority of l-alpha-tocopherol is due, at least in part, to a faster rate of loss from the body.

Phosphate Metabolism in Nutritional Muscular Dystrophy and Hyperthyroidism.

Summary 1) Rabbits and rats were made Vit. E-deficient by feeding a purified diet. Control animals received the same diet supplemented with Vit. E. Hyperthyroidism was induced in rats by giving subcutaneous injections of sodium thyroxinate. Control and experimental animals from each group were injected with P32 in dilute HCl and specific activities of plasma inorganic phosphate, and skeletal muscle inorganic phosphate, creatine phosphate, and ATP phosphate determined. The S. A. of the plasma inorganic phosphate was unchanged by Vit. E deficiency and was decreased by hyperthyroidism. Skeletal muscle inorganic phosphate S. A. was increased by Vit. E deficiency and the difficulties in interpreting these data were discussed. The S. A. of phosphates of creatine phosphate and ATP phosphate were high in both Vit. E deficient rabbits and hyperthyroid rats. The significance of these findings was discussed in relation to turnover of creatine phosphate and ATP. 2) These experiments indicate that there is an elevated turnover of skeletal muscle intracellular inorganic phosphate and a normal or decreased turnover of skeletal muscle creatine phosphate and ATP in Vit. E deficiency. In contrast there appears to be no depression in turnover of creatine phosphate and ATP in hyperthyroid rats.

Influence of vit. E deficiency in rabbit on urinary excretion of free amino acids.

Summary Vit. E deficiency in the rabbit results in increased excretion of free amino acids in urine. This increase in amino acid excretion is apparent before any physical signs of dystrophy are observed.

Vitamin E Deficiency in the Monkey. VI. Metabolism of Greatine-1-G14.

Summary After creatine-1-C14 injection half-times of body creatine of 38, 40, and 51 days were found in 3 normal rhesus monkeys. Three vitamin E-deficient monkeys had shortened half-times of body creatine: 20, 21, and 23 days. This abnormality points to a defect in the ability of skeletal muscle to retain creatine as the explanation for the low concentration of creatine in muscle of vitamin E-deficient animals.