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From a review titled Cerebral Folate Deficiency Syndrome: Early Diagnosis, Intervention and Treatment Strategies, from Table 1:

V. Conditions affecting folate metabolism in the brain

  1. Hereditary conditions
    Depletion of methyl-donor pool glycine, serine, and histidine

I don't understand the meaning of the line in bold. How could glycine, serine and histidine be related to "depletion of the methyl donor pool"? Are they donors of methyl groups? I googled, and it does not seem so.

A snapshot of the table, with my highlighting:

enter image description here

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    Yes, serine is a methyl group donor, most importantly to the author for THF. Panel A of this figure from Wikipedia shows how. Glycine also, through glycine N-methyltransferase. Not sure of histidine off the top of my head.
    – Ian Campbell
    Sep 15, 2022 at 17:10
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    You might have better luck searching in Google Scholar, which limits the hits significantly. Sep 15, 2022 at 17:11
  • Thank you! I'll try googling it up on Scholar! Sep 15, 2022 at 17:14

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THF (Tetrahydrofolate) is the active form of folic acid. THF serves as an acceptor and donor of one carbon units and acts as a coenzyme in such reactions. One carbon metabolism helps in the synthesis of various important compounds like purines, pyrimidine which are used in DNA synthesis and various amino acids. One carbon units are attached to it's 5 and 10 position.

I don't understand the meaning of the line in bold. How could glycine, serine and histidine be related to "depletion of the methyl donor pool"? Are they donors of methyl groups? I googled, and it does not seem so.

Well, they don't actually donate methyl groups but are indirectly related. They donate different one carbon units.

  • Glycine and tryptophan donate formate group which combines with THF to form N10-formyl THF. During conversion of serine to glycine, THF gets converted to methylene-THF.
  • Histidine after a series of reactions get converted to FIGLU (Formiminoglutamate). THF acts on FIGLU to form N5-formimino THF and glutamate.

These forms of THF are interconvertible. From methylene-THF, methyl-THF is formed which is the abundant form in circulation and acts as a methyl donor.

Reference:

Ducker, G. S., & Rabinowitz, J. D. (2017). One-Carbon Metabolism in Health and Disease. Cell metabolism, 25(1), 27–42. https://doi.org/10.1016/j.cmet.2016.08.009

PMCID: PMC5353360, NIHMSID: NIHMS852041, PMID: 27641100

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