The effect of homocysteine, methionine, serine and glycine on DNA synthesis by human normoblastic and megaloblastic bone marrow cells.

Taguchii, Hirokuni; Chanarin, I.

doi:10.3177/jnsv.24.83

Cited by 12 publications

(9 citation statements)

References 17 publications

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“…Similarly in man (8), methionine was found to reduce the urinary excretion of FIGLU in cobalamin deficiency. Surprisingly, however, methionine failed to correct the deranged DNA synthesis by bone marrow cultures in cobalamin deficiency in both humans and animals (9)(10)(11)(12)(13).…”

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confidence: 99%

“…The effect of low 0.27 pmol (40 pg) and high 6.7 kmol (1 mg) amounts of methionine were therefore tested in bone marrow cultures from patients with cobalamin deficiency, folate deficiency and in control subjects. In these patients DNA synthesis by bone marrow cells is deranged as measured by the deoxyuridine (dU) suppression test (9, 10,12,[17][18][19][20]. Although the precise biochemical basis of the dU suppression test is not completely understood (21)(22)(23) this test remains a sensitive method to define biochemical megaloblastosis (23)(24)(25).…”

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confidence: 99%

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Regulation of Cobalamin and Folate Metabolism by Methionine in Human Bone Marrow Cultures

Sourial

Brown

1983

Scandinavian Journal of Haematology

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In cobalamin deficiency folate metabolism is disturbed. In the liver this deranged metabolism can be overcome by methionine, however, methionine failed to overcome this abnormality in bone marrow cultures from cobalamin deficient patients. In cobalamin deficient E. coli mutant bacteria, methionine under different conditions could either inhibit or potentiate the growth of the organism. This study was therefore initiated to test the effect of methionine, under different conditions, on bone marrow cultures. The defective DNA synthesis in megaloblastic bone marrow due to cobalamin deficiency could be corrected by the in vitro addition of low 0.27 μmol (40 μg) but not high 6.7 μmol (1 mg) amounts of methionine. This was measured by the ability of deoxyuridine to suppress the 3H‐thymidine incorporation into DNA. The effect of methionine in facilitating de novo DNA synthesis is probably due to the catalytic action of SAM which activates cobalamin dependent methyltransferase enzyme thus potentiating the effect of cobalamin. In contrast high concentrations of methionine may inhibit this enzyme.

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confidence: 99%

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confidence: 99%

Regulation of Cobalamin and Folate Metabolism by Methionine in Human Bone Marrow Cultures

Sourial

Brown

1983

Scandinavian Journal of Haematology

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“…In contrast to the corrective effect of small doses of methionine, large doses seem to further impair the defective DNA synthesis produced by N20 anaesthesia. Large doses may decrease dU incorporation into DNA synthesis (20) and inhibit the methionine synthetase enzyme (21). Nitrous oxide and methionine may have a synergistic effect on depletion of functional folates, and may therefore be of value in the treatment of cancer patients ( 5 ) .…”

Section: Discussionmentioning

confidence: 99%

Role of S‐adenosylmethionine in DNA synthesis and haemopoiesis

Sourial

Amess

Amos

1985

Scandinavian Journal of Haematology

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In man, exposure to nitrous oxide (N20) can produce neurological damage and megaloblastic change in the bone marrow due to inactivation of vitamin BI2. Methionine metabolism is interrelated with that of vitamin B,2 and folate; the effect of methionine on the impaired DNA synthesis produced by N 2 0 was therefore studied in 17 patients undergoing surgery. 14 were anaesthetised with 50% N 2 0 in oxygen for 3-24 h. The remaining 3 had been exposed to N 2 0 for less than 3 h. All patients developed megaloblastic bone marrow change except 2 of the latter patients whose bone marrows remained normoblastic.The bone marrow was studied biochemically using the deoxyuridine (dU) suppression test. The in vitro addition of small doses of methionine was as effective as vitamin B,, itself in correcting the defective DNA synthesis produced by N20. It is suggested that N 2 0 impairs methionine biosynthesis, rnethionine, in the form of S-adenosylmethionine (SAM), being required for DNA synthesis and the prevention of the development of megaloblastic anaemia in man, CLINICAL BEARINGThe rate of development and severity of megaiobiastic anaemia in cobalamin deficiency or in that produced by nitrous oxide anaesthesia may be related to the dietary intake and body reserves of methionine. Low doses of methionine may potentiate the in vivo effect of cobalamln. It may prove useful to include both methionine and foiate in parented feeding of patients in intensive care who are slow to recover from the effects of nitrous oxide anaesthesia.

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“…In fact, moderate increases in methionine intake for 10 weeks have been reported to result in atherogenesis per se in ApoE-deficient mice, independent of elevated plasma homocysteine. In this same animal model, the combination of excess methionine intake and low folate, B 6 and B 12 diets exacerbated the effect of methionine. It was therefore suggested that, although homocysteine might contribute to the effect of methionine, high plasma homocysteine was not independently atherogenic in the animal model studied [17] .…”

Section: Introductionmentioning

confidence: 97%

“…Classical studies have described depressions in growth and food intake, as well as lesions of the liver, spleen, kidney, pancreas and small intestine when excessive doses are given to experimental animals [3] . At the cellular level, methionine has been shown to lower the de novo synthesis of thymidylate and thymine-DNA in bone marrow cells [4][5][6] . It has also been reported that high concentrations of L -methionine inhibit the de novo synthesis of thymidilic acid in Raji cells, a Burkitt lymphoma cell line [7] .…”

Section: Introductionmentioning

confidence: 99%

Mild Methionine Excess Does Not Affect Thymidylate Synthesis or Inflammation Markers Expression in Human Aortic Endothelial Cells

et al. 2009

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Background: Recent studies in animal models have shown that high methionine intakes induce atherosclerotic changes that may be exacerbated when deficiencies of vitamins B₆, B₁₂ and folate are present. However, the mechanism underlying this possible atherogenic effect remains unknown. The aim of the present study was to evaluate the effects of methionine on the folate-dependent thymidylate-DNA synthesis, as a possible mechanism of atherogenicity, as well as the effect of high methionine/low folate on several key inflammation markers, such as vascular cell adhesion molecule-1 (VCAM-1), receptor for advanced glycation end products (RAGE) and matrix metalloproteinase-9 (MMP-9) in human aortic endothelial cells. Methods: Deoxyuridine suppression test was performed in order to evaluate thymidylate synthesis. To examine the expression of inflammation markers, cells were exposed to high methionine/low folate media for 9 days. Results: The assayed methionine levels (0.1, 0.5 and 5 mM) did not affect the de novo thymidylate-DNA synthesis. Consistent with this result, methionine (1 and 2.5 mM), alone or in combination with folate deficiency, increased homocysteine levels but did not induce the expression of the inflammation markers evaluated. Conclusion: Under the study conditions, methionine was not able to exert the atherogenic mechanism proposed and did not have the hypothesized inflammatory consequences in human aortic endothelial cells.

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The effect of homocysteine, methionine, serine and glycine on DNA synthesis by human normoblastic and megaloblastic bone marrow cells.

Cited by 12 publications

References 17 publications

Regulation of Cobalamin and Folate Metabolism by Methionine in Human Bone Marrow Cultures

Regulation of Cobalamin and Folate Metabolism by Methionine in Human Bone Marrow Cultures

Role of S‐adenosylmethionine in DNA synthesis and haemopoiesis

Mild Methionine Excess Does Not Affect Thymidylate Synthesis or Inflammation Markers Expression in Human Aortic Endothelial Cells

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