Nucleic acids metabolism, in vitamin E deficiency

J. S. Dinning Nucleic Acid Metabolism in Vitamin E Deficiency. 511... 

Many years ago Adamstone (1934, 1936) suggested, after extensive histopathologic study of vitamin E-deficient chickens, that the vitamin must exert some controlling influence over cellular proliferation. Mason (1944) carried this suggestion further and hypothesized that vitamin E might somehow influence the synthesis of nuclear chromatin. After these suggestions, which were made almost 30 years ago, there were no experimental studies of nucleic acid metabolism in vitamin E deficiency until the experiments to be described in this review were undertaken. 

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 multi-nucleated cells in rat testes (Mason, 1933), and the appearance of many multinucleated erythroid precursors in vitamin E-deficient monkey bone marrow (Porter et 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 (Dinning and Day, 1957a). 

In vitamin Bg-deficient experimental animals, there are skin lesions (e.g., acrodynia in the rat) and fissures or ulceration at the corners of the mouth and over the tongue, as well as a number of endocrine abnormcdities defects in the metabolism of Uyptophan (Section 9.5.4), methionine (Section 9.5.5), and other amino acids hypochromic microcytic anemia (the first step of heme biosynthesis is pyridoxal phosphate dependent) changes in leukocyte count and activity a tendency to epileptiform convulsions and peripheral nervous system damage resulting in ataxia and sensory neuropathy. There is also impairment of immune responses, as a result of reduced activity of serine hydroxymethyltransferase and hence reduced avtdlability of one-carbon substituted folate for nucleic acid synthesis (Section 10.3.3). It has been suggested... 

The results of all these experiments with rabbits may be explained as being due to an increased synthesis of DNA in skeletal muscle of the vitamin E-deficient animals with no appreciable change in the nucleic acid metabolism of other tissues. This increased rate of DNA synthesis in skeletal muscle from vitamin E-deficient animals would require an accelerated rate of synthesis of acid-soluble nucleotides, which in turn could result in higher specific activities of nucleic acids isolated from other tissues... 

The influence of vitamin E deficiency on nucleic acid metabolism has been investigated in rats, rabbits, and monkeys. The concentrations of both RNA and DNA are elevated in skeletal muscle and bone marrow. From studies with a variety of radioactive nucleic acid precursors it is concluded that vitamin E deficiency leads to an increased rate of DNA synthesis in rabbit skeletal muscle and in monkey skeletal muscle and bone marrow. These changes in nucleic acid metabolism may be related to the... 

The chemistry, metabolism, and clinical importance of folic acid have been the subject of many excellent reviews (A7, Gil, H14, H20, Rl). Folic acid deficiency leads to a macrocytic anemia and leucopenia. These symptoms are due to inadequate synthesis of nucleic acid. The synthesis of purine bases and of thymine, required for nucleic acid synthesis, is impaired in folic acid deficiency. Detection of folic acid activity in biologic fluids and tissues is of the utmost importance it distinguishes between the various anemias, e.g., those due to vitamin Bi2 or folic acid deficiency. Because morphology of the abnormal red cell does not help in diagnosing vitamin deficiency, one must rely on assay methods for differential diagnosis. Treatment of pernicious anemia with folic acid has led to subacute combined degeneration of the spinal cord despite... 

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