John M. Noronha

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.

Elevated urinary levels of 6‐hydroxymethylpterin during malignancy and liver regeneration: A simple, noninvasive test for cancer detection

A simple and rapid method for determining urinary 6‐hydroxymethylpterin levels is described. It involves adsorption of the pterin compound from deproteinized urine samples on activated charcoal under acidic conditions and its subsequent elution under alkaline conditions in a concentration suitable for its spectrophotofluorometric quantitation. The major blue fluorescent compound being measured was identified as 6‐hydroxymethylpterin by thin layer chromatography on combined Silica gel‐G and cellulose. While 30 healthy human subjects excreted 6‐hydroxymethylpterin at a mean level of 0.121 μg/ml of urine, 120 patients with various types of cancer excreted very significantly higher levels ranging from 0.3 to 2.0 μg/ml. The mean excretion level for 19 patients with various nonmalignant diseases was 0.134 μG/ml which was not significantly different from that for the healthy control subjects. In two experimental model systems described, following partial hepatectomy and the induction of Yoshida ascites tumors in rats, the peak periods of liver regeneration and maximal tumor growth were accompanied, respectively, by four and 40‐fold increases in urinary 6‐hydroxymethylpterin excretion. Ingestion of multivitamin tablets containing 5 mg of folic acid (but not rich dietary sources of folates) resulted in temporary elevation of urinary 6‐hydroxymethylpterin levels. The method described for determining urinary 6‐hydroxymethylpterin provides a simple, noninvasive means of detecting prevailing malignancies.

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.

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.