James S. Dinning

Vitamin E deficiency in the monkey: VII. The role of vitamin E and the vitamin-like activity of coenzyme Q☆

Abstract Young Rhesus monkeys were fed a vitamin E-deficient purified diet containing, by weight, 11% fat and 18% isolated soybean protein. After 1–2 years they developed the characteristic deficiency syndrome of nutritional muscular dystrophy and anemia. The syndrome was not influenced by extra dietary methionine and cystine, by the presence or absence of choline, or by selenium. Complete remission of the muscular dystrophy and anemia was induced either by d -alpha-tocopherol or by its l -epimer, but the duration of the remission after treatment with the l -epimer was relatively short. Coenzyme Q 10 treatment evoked a reticulocytosis in the anemic, vitamin E-deficient monkey, and a complete hematologic remission followed treatment with a compound of lower molecular weight, hexahydrocoenzyme Q 4 . This response was interpreted to mean that vitamin E either is involved in the maintenance of coenzyme Q activity or can substitute for coenzyme Q.

Iron deficiency in monkeys fed diets containing soybean protein.

Summary After receiving purified diets containing isolated soybean protein for 2 to 7 months, young Rhesus monkeys (Macaca mulatta) became anemic. The erythrocytes were microcytic and hypochromic, serum iron concentrations were low and serum iron binding capacities were high. Iron therapy, either parenteral or oral, produced a prompt remission of anemia. Since these diets contain as much iron as other diets that are adequate in this respect, gastrointestinal absorption of Fe59 was evaluated in the presence of soybean protein and compared to Fe59 absorption in the presence of casein. Soybean protein caused a significant reduction in gastrointestinal absorption of Fe59.

Nucleic Acid Metabolism in Vitamin E Deficiency

Publisher Summary Certain aspects of the pathology of vitamin E deficiency suggest that nucleic acid metabolism may be deranged. In tissues severely affected by the deficiency one sees various nuclear changes. These include an increase in numbers of nuclei in rabbit skeletal muscle, appearance of giant multinucleated cells in rat testes (Mason, 1933), and the appearance of many multinucleated erythroid precursors in vitamin E-deficient monkey bone marrow (Porter el al., 1962). It is of course well known that these tissues are dramatically affected by vitamin E deficiency in the various species. In the rabbit one sees nutritional muscular dystrophy, in the male rat sterility, and in the monkey macrocytic anemia. Authors investigated the influence of vitamin E deficiency on tissue nucleic acid concentrations in these species and on the synthesis of nucleic acids as measured by the incorporation of various radioactive precursors.

Nucleic acid metabolism in mice with hereditary muscular dystrophy.

Abstract Swiss mice, S-129 mice with hereditary muscular dystrophy, and their normal litter mates were injected with formate-C 14 , and groups were killed 1, 3, 5, and 7 days after injection. Urine was collected for determination of quantity and radioactivity of allantoin. DNA and RNA concentration and specific activities were determined in liver, small intestine, and skeletal muscle. There were no differences among the three groups in allantoin excretion per unit body surface or in allantoin specific activity. Skeletal muscle from dystrophic mice contained approximately three times as much DNA and two times as much RNA per unit wet weight as did S-129 control mice or Swiss mice. The turnover time of skeletal muscle DNA or RNA was not shortened in dystrophic mice. The results indicate that nucleic acid turnover is not increased in skeletal muscle of mice with hereditary muscular dystrophy in contrast to the situation in animals with nutritional muscular dystrophy. This suggests that the hereditary muscular dystrophy in mice is not related to an inability to utilize vitamin E.

Relative effectiveness of B12 and dimethylbenzimidazole B12-coenzyme in thymine methyl biosynthesis.

SummaryVit. B12 was more effective in stimulating conversion of formate to thymine methyl by chick bone marrow cells than was 5,6 dimethylbenzimidazole B12-coenzyme.Summary Vit. B12 was more effective in stimulating conversion of formate to thymine methyl by chick bone marrow cells than was 5,6 dimethylbenzimidazole B12-coenzyme.

Creatine Metabolism in Hyperthyroidism.

Summary Hyperthyroidism was induced in rats by thyroxine injections and by feeding of desiccated thyroid. Normal and hyperthyroid rats were injected with glycine-1-C14 and incorporation of the isotope into glycocyamine and creatine was determined. In other experiments normal and hyperthyroid rats were injected with creatine-1-C14 and its incorporation into skeletal muscle and heart creatine was determined. Hyperthyroidism resulted in an increased creatinuria, and increased heart weight and a decreased heart creatine concentration. Hyperthyroidism led to increased incorporation of glycine into liver creatine and to decreased incorporation into skeletal muscle and heart creatine. It is concluded that the creatinuria of hyperthyroidism is the result of a block in incorporation of creatine into skeletal muscle and cardiac muscle.

Pteroylglutamic acid, ascorbic acid, and injectable liver extract on dietary glycine toxicity in the rat.

Summary Weanling albino rats were fed a standard purified diet, and a similar diet containing 10% glycine replacing an equal amount of sucrose. Groups of rats were given j the glycine-containing diet supplemented respectively with PGA, injectable liver extract, PGA plus liver extract, and ascorbic acid. The growth of rats receiving the high glycine diet was greatly reduced as compared to the control group. Supplementation of the high glycine diet with PGA and with PGA plus liver extract resulted in a marked improvement in growth rate; liver extract alone was less effective; and ascorbic acid did not significantly improve rate of growht of rats receiving the 10% glycine diet. Rats receiving the high glycine diet did not develop a marked leucopenia when compared with control rats; however, supplementation of this diet with PGA resulted in an increased white count while supplementation with liver extract and with liver extract pluw PGA resulted in an increased white count in male rats but was without effect in females. The mean corpuscular volume was found to be highest in rats receiving the high glycine diet plus ascorbic acid.

Effects of 5-Br-deoxyuridine and 5-F-deoxyuridine on nucleic acid metabolism by rabbit bone marrow cells.

Summary The effects of 5-Br-deoxyuridine and 5-F-deoxyuridine on thymidine-2-C14, formate-C14, and P32 incorporation into rabbit marrow DNA in vitro were studied. 5-Br-deoxyuridine competitively inhibits incorporation of thymidine-2-C14 into rabbit marrow DNA, and is apparently used in lieu of thymidine for DNA biosynthesis. The bone marrow is quite sensitive to the action of 5-Br-deoxyuridine. 5-F-deoxyuridine does not appreciably affect incorporation of thymidine-2-C14 or P32 into marrow DNA or formate-C14 into RNA but greatly inhibits utilization of labeled formate for DNA synthesis indicating an interference with thymidine formation.

A substance in liver which inhibits thymine biosynthesis by bone marrow.

A substance was extracted from rabbit liver which inhibited the incorporation of formate into bone-marrow thymine in vitro. In view of the important role of thymine biosynthesis in cell division, it is suggested that the inhibitor present in liver is a naturally occurring mitosis inhibitor.

Effect of Diet on Rat Liver Betaine Transmethylase

Summary 1. Rat liver betaine transmethylase varies strikingly with the amino acid composition of the diet. 2. The pattern of amino acids required for synthesis of this enzyme is considerably different from the pattern required for growth of the animal. 3. When rats are given methionine, betaine transmethylase does not appear to be necessary for growth.