Methionine but Not Folinic Acid or Vitamin B-12 Alters the Frequency of Neural Tube Defects in Axd Mutant Mice

Essien, Francine B.; Wannberg, Sharon

doi:10.1093/jn/123.1.27

Cited by 104 publications

(43 citation statements)

References 25 publications

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“…Differences in homocysteine levels among cases and control children may be difficult to detect since homocysteine levels are age dependent [Vilaseca et al, 1997]. Although homocysteine itself may be teratogenic [Rosenquist et al, 1996], other possibilities include deficient synthesis of methionine or S-adenosylmethionine [Essien and Wannberg, 1993], an important component in many methylation reactions.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects

et al. 1999

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Folic acid administration to women in the periconceptional period reduces the occurrence of neural tube defects (NTDs) in their offspring. A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), 677C-->T, is the first genetic risk factor for NTDs in man identified at the molecular level. The gene encoding another folate-dependent enzyme, methionine synthase (MTR), has recently been cloned and a common variant, 2756A-->G, has been identified. We assessed genotypes and folate status in 56 patients with spina bifida, 62 mothers of patients, 97 children without NTDs (controls), and 90 mothers of controls, to determine the impact of these factors on NTD risk. Twenty percent of cases and 18% of case mothers were homozygous for the MTHFR polymorphism, compared to 11% of controls and 11% of control mothers, indicating that the mutant genotype conferred an increased risk for NTDs. The risk was further increased if both mother and child had this genotype. The MTR polymorphism was associated with a decreased O.R. (O.R.); none of the cases and only 10% of controls were homozygous for this variant. Red blood cell (RBC) folate was lower in cases and in case mothers, compared to their respective controls. Having a RBC folate in the lowest quartile of the control distribution was associated with an O.R. of 2.56 (95% CI 1.28-5.13) for being a case and of 3.05 (95% CI 1.54-6.03) for being a case mother. The combination of homozygous mutant MTHFR genotype and RBC folate in the lowest quartile conferred an O.R. for being a NTD case of 13.43 (CI 2.49-72.33) and an O.R. for having a child with NTD of 3.28 (CI 0.84-12.85). We propose that the genetic-nutrient interaction--MTHFR polymorphism and low folate status--is associated with a greater risk for NTDs than either variable alone.

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Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects

et al. 1999

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“…Indeed, when rat embryos were exposed in culture to valproic acid the cytoskeletal proteins actin and ␣␤-tubulin failed to localize in the basal cytoplasm of the neural ectoderm cells similar to that observed here with methionine deficiency (unpublished observation). Regarding genes, to date only the Axd mouse mutant susceptible to neural tube defects has been reported to respond to methionine supplements with reductions in the occurrence of neural tube defects (39). Methionine supplements would also be expected to circumvent the incidence of neural tube defects caused by mutations in the 5,10-methylenetetrahydrofolate reductase enzyme.…”

Section: Discussionmentioning

confidence: 99%

Effects of methionine on the cytoplasmic distribution of actin and tubulin during neural tube closure in rat embryos

Moephuli

Klein

Baldwin

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Research has previously shown that, without methionine supplements, neural tube proteins of rat embryos cultured on bovine sera were hypomethylated and neural tubes failed to close. In the present study, to identify the proteins that became methylated during neurulation, rat embryos were first cultured on methionine-deficient bovine serum for 40 hr, then incubated with puromycin for 1 hr, and, finally, incubated with [methyl-14 C]methionine and puromycin for 5 hr. On the basis of molecular weights, isoelectric points, and Western immunoblots, the methyl-14 C-labeled proteins were identified as actin, ␣␤-tubulin, and neurofilament L. Indirect immunof luorescence studies indicated that without the addition of methionine to the culture, localization of actin and ␣␤-tubulin in the basal cytoplasm did not occur and these neuroepithelial cells lost their columnar morphology.

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“…Methionine: Precursor of glutathione (200) ; precursor of S-adenosyl methionine (653) ; neural tube defects (654) ; colon cancer (410) ; cognitive impairment in situation of folate deficiency (653) ; antioxidant activity (655) ; lipotrope (239) Cystine: Hair and nail development (656,657) ; muscle wasting (658) ; antioxidant and cell signalling through reactive cysteine residues in proteins (659) Total fibre (18,46,58,266,660,661) :…”

Section: Appendixmentioning

confidence: 99%

New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?

2010

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Epidemiological studies have clearly shown that whole-grain cereals can protect against obesity, diabetes, CVD and cancers. The specific effects of food structure (increased satiety, reduced transit time and glycaemic response), fibre (improved faecal bulking and satiety, viscosity and SCFA production, and/or reduced glycaemic response) and Mg (better glycaemic homeostasis through increased insulin secretion), together with the antioxidant and anti-carcinogenic properties of numerous bioactive compounds, especially those in the bran and germ (minerals, trace elements, vitamins, carotenoids, polyphenols and alkylresorcinols), are today well-recognised mechanisms in this protection. Recent findings, the exhaustive listing of bioactive compounds found in whole-grain wheat, their content in whole-grain, bran and germ fractions and their estimated bioavailability, have led to new hypotheses. The involvement of polyphenols in cell signalling and gene regulation, and of sulfur compounds, lignin and phytic acid should be considered in antioxidant protection. Whole-grain wheat is also a rich source of methyl donors and lipotropes (methionine, betaine, choline, inositol and folates) that may be involved in cardiovascular and/or hepatic protection, lipid metabolism and DNA methylation. Potential protective effects of bound phenolic acids within the colon, of the B-complex vitamins on the nervous system and mental health, of oligosaccharides as prebiotics, of compounds associated with skeleton health, and of other compounds such as a-linolenic acid, policosanol, melatonin, phytosterols and para-aminobenzoic acid also deserve to be studied in more depth. Finally, benefits of nutrigenomics to study complex physiological effects of the 'whole-grain package', and the most promising ways for improving the nutritional quality of cereal products are discussed. Whole-grain wheat: Bioactive compounds: Physiological mechanisms: Health IntroductionThere is growing evidence that whole-grain cereal products protect against the development of chronic diseases. The most important of these in terms of public health are obesity (1,2) , the metabolic syndrome (3,4) , type 2 diabetes (5,6) , CVD (7) and cancers (8 -12) . Whole-grain cereal consumption has also been shown to be protective against mortality, as was shown with inflammation-related death (i.e. noncardiovascular and non-cancer inflammatory diseases such as, for example, respiratory system diseases) (13) and with cancer and CVD (4,14,15) . These conclusions are supported by the effects of consuming refined cereal products (bread, pasta and rice), as these have been associated with an increased risk of digestive tract, pharynx, larynx and thyroid cancers in northern Italians (16) . However, an association between a lower risk of developing a chronic disease and a high whole-grain cereal consumption does not mean a direct causal relationship and provides no information about the physiological mechanisms involved.These metabolic diseases are related to our daily lifestyle, no...

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Methionine but Not Folinic Acid or Vitamin B-12 Alters the Frequency of Neural Tube Defects in Axd Mutant Mice

Cited by 104 publications

References 25 publications

Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects

Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects

Effects of methionine on the cytoplasmic distribution of actin and tubulin during neural tube closure in rat embryos

New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?

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