Gomathy Viswanathan

Folate-mediated incorporation of ring-2-carbon of histidine into nucleic acids: influence of thyroid hormone.

Folate-mediated incorporation of [ring-2-14C]histidine into DNA and its modulation under thyroid stress have been studied. Both hyperthyroidism and hypothyroidism decrease the folate-mediated incorporation of the one-carbon unit derived from histidine into DNA significantly, resulting in growth retardation. In concurrence with previous reports, in vivo oxidation of histidine is decreased in hyperthyroidism and increased in hypothyroidism. 5,10-Methylenetetrahydrofolate reductase levels are elevated in hyperthyroidism and decreased in hypothyroidism, whereas methionine synthase levels are decreased in hyperthyroidism and increased in hypothyroidism. It is discussed how in both hyperthyroidism and hypothyroidism folate cofactor-mediated reactions are adversely affected.

Variations in Folate Metabolism in Whole Body γ-Irradiated Mice

Abstract Folate metabolism has been studied in 7 Gy whole body y-irradiated mice. Considerable changes in the formyl and methyl tetrahydrofolate derivatives were observed in the liver at various stages after irradiation. Methyltetrahydrofolate polyglutamate cofactors were reduced to a considerable extent in the irradiated group. Significant levels of oxidized folates such as pteroyl mono-, di-, and tetra- glutamyl forms were found only in the irradiated liver indicative of oxidative changes. Methylenetetrahydrofolate reductase, the enzyme synthesizing methyltetrahydrofolates was impaired 35-40% in irradiated animals possibly leading to an impairment in methyltetrahydrofolate synthesis. Folylpolyglutamate hydrolase which hydrolyzes polyglutamylfolates to simpler forms, showed an immediate spurt in the activity but returned to normal values, 48-72 h after irradiation. An increased lysosomal membrane damage as assessed by higher free-amino acid pool was observed in irradiated mice.

Impaired Folic Acid Metabolism Leading to Increased Urinary Folate Loss in Streptozotocin-induced Diabetic Rats

Summary Streptozotocin-induced diabetes resulted in the alteration of an overall hepatic folate metabolism In rats leading to an increased urinary excretion of folates, mainly of methyl formas.

Antiatherogenic Effect of Folic Acid in Alcoholism

Folic acid has been reported to have a protective role against atherosclerosis in man and rats (1). The lipoprotein profiles of hypertensive and diabetic subjects have been reported earlier from our laboratory (2). Higher levels of total cholesterol (TC), total triglycerides (TG), very low density lipoprotein cholesterol (VLDLC), low density lipoprotein cholesterol (LDLC) and TC/HDLC (high density lipoprotein cholesterol) ratio of greater than 5 are known to be associated with increased risk of atherogenesis (3). A decreased lipoprotein lipase activity which hydrolyses the core triglycerides in chylomicrons and very low density lipoproteins, is also observed to be associated with coronary heart disease (3). We report here the plasma lipase and lipoprotein profiles in alcohol fed folate deficient (4) rats with and without folate supplementation.

Studies on a membrane-bound and solubilized ribonucleotide reductase preparation from Escherichia coli Tau−

Ribonucleotide reductase has been shown to be associated with the DNA-membrane complex in Escherichia coli TAU- cells. The membrane-bound enzyme has been released in a soluble form using a combined treatment of 1% sarcosyl (pH 8.0) and 1% sodium deoxycholate (pH 6.5). Allotropic differences in the modulatory effects of ATP, Mg2+, EDTA and dithiothreitol on the membrane-bound and solubilized enzyme activity are discussed.

Varying Folate Pattern in Different Strains of Mice Fed Coconut Oil and Sesame Seed Oil Diet

Summary The effect of coconut oil feeding with and without cholesterol on folate metabolism in the two strains of mice, C57BL/6 and AKR have been studied. Liver total folate levels are higher in AKR mice. Coconut oil feeding markedly decreased the ratio of nonmethyl/methyl folates in C57BL/6 strain but not in AKR. Cholesterol supplementation to the coconut oil diet increased the percentage of monoglutamyl folates at the expense of polyglutamyl folates in both strains. Only C57BL/6 strain showed growth retardation on coconut oil feeding. The differences in hepatic folate metabolism between the two strains could possibly have an important role in determining their differences in susceptibility to diet induced atherosclerosis.

Role of Folate in the Modulation of Lipids, Lipoproteins and Eicosanoids in Hypertension and Diabetes

Summary Besides elevated levels of lipids and lipoproteins, ievels of the physiological amino acid homocysteine as well as whole blood folates are now known to play a role in atherogenesis. The role of folates in atherosclerosis is rather peculiar in that it helps to catalyse the remethylation of homocysteine (a proatherogenic agent) to methionine thus preventing the accumulation of homocysteine in plasma and hence its antiatherogenic role. We estimated whole blood folate levels of 69 normotensive, 34 diabetic and 94 hypertensive individuals and have attempted to correlate these values with lipid and non-lipid parameters. Whole blood levels of simple, conjugated and total folates were significantly higher among the diabetics as well as the hypertensives when compared to the normotensives. In all the study groups, levels of conjugated folates correlated significantly to those of total folates even after adjustments for age and body mass index were introduced. Among the normotensive individuals the significance of the inverse correlation between simple folates and total cholesterol/high density lipoprotein cholesterol ratio was lost after adjusting for age and body mass index. Levels of total and conjugated folates were positively correlated to plasma levels of thromboxane B2 among the diabetics. In the same group the positive correlation between total folates and thromboxane B2 and that between total folates and the eicosanoid ratio remained significant even after adjustments for age and body mass index were introduced. None of the other metabolic variables correlated with whole blood levels of simple folates in any of the study groups.

Ribonucleotide reductase levels, deoxyribonucleotide pools and nucleic acid patterns during Dysdercus koenigii embryogenesis

Abstract Increases in DNA and RNA content were observed during the course of embryonic development of Dysdercus koenigii. DNA reaches maximum levels at 90 h and RNA at around 120 h of development. The activity of ribonucleotide reductase was first detected around 20 h of development after depletion of the low levels of deoxyribonucleotides present initially (20–70 pmol/egg). The pattern of its activity fits the rise of DNA levels. Incorporation of labelled cytidine into DNA and RNA reached a maximum in the 90-h-old embryos (roughly the same time as the peak rise in ribonucleotide reductase level and DNA content). The changes in individual deoxyribonucleotide levels observed during development of this insect embryo can be correlated to the periodic spurts in DNA increase.