1. Serine hydroxymethyltransferase
2. Thymidylate synthase
3. Dihydrofolate reductase
4a. 5,10-methylenetetrahydrofolate dehydrogenase NADP+
4b. 5,10-methenyltetrahydrofolate cyclohydrolase
4c. Formate-tetrahydrofolate ligase
5. Phosphoribosylaminoimidazolecarboxamide formyltransferase
6. Methylenetetrahydrofolate reductase
7. Methionine synthase
N.B. 4a-c are three components of MTHFD1
Where does Vitamin U fit into all this? It should be emphasized that there has not been any scientific research testing whether Vitamin U supplementation can prevent NTDs. The studies have simply not been done. However, there is some genetic evidence that suggests that Vitamin U may play a role in correct neural tube formation.
- Vitamin U supplies methyl groups to mammals via its reaction with homocysteine to form methionine catalyzed by the enzyme BHMT2. This is very similar to that of betaine, though whether Vitamin U plays this role in embryonic tissue has not been investigated.
- Vitamin U is abundant in vegetables, the benefits of which have been long known in preventing neural tube defects. While the presence of folate is most likely the primary factor, it is possible that some of the benefits conferred by eating vegetables are due to the provision of methyl groups from Vitamin U.
- A preconception diet rich in methionine reduces the prevalence of neural tube defects. Vitamin U is essentially methionine with an extra methyl group. One molecule of Vitamin U actually supplies two molecules of methionine, one being the newly-methylated homocysteine, the other being the demethylated Vitamin U.
- Studies have shown that methylation in the embryo is supplied by methyl groups from both the folate cycle and betaine. If we assume that methionine synthase and BHMT1 contribute to embryonic methylation, then Vitamin U is also likely to make a contribution. It is logical that the benefits of green vegetables in preventing neurological abnormalities is due to the combined effects of folate, betaine and Vitamin U, with the emphasis on folate.
- Folate is absolutely necessary at some level to provide the embryo nucleotides during the first weeks following conception. It cannot be replaced by other molecules.
- Folate requirements may be lowered as long as adequate levels of methyl groups are provided by methionine and betaine from the methionine cycle.
- Though its role in fetal development has not been investigated, it is likely that Vitamin U has a similar role to that of methionine and betaine, and would be of greater importance for people whose diet is low in protein and fat such as vegans.
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- Zhang et al 2015 https://pubmed.ncbi.nlm.nih.gov/25466894/
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