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Review
. 2019 Feb 4;216(2):253-266.
doi: 10.1084/jem.20181965. Epub 2018 Dec 26.

Toward a better understanding of folate metabolism in health and disease

Yuxiang Zheng  1 , Lewis C Cantley  2
Affiliations
Review

Toward a better understanding of folate metabolism in health and disease

Yuxiang Zheng et al. J Exp Med. .

Abstract

Folate metabolism is crucial for many biochemical processes, including purine and thymidine monophosphate (dTMP) biosynthesis, mitochondrial protein translation, and methionine regeneration. These biochemical processes in turn support critical cellular functions such as cell proliferation, mitochondrial respiration, and epigenetic regulation. Not surprisingly, abnormal folate metabolism has been causally linked with a myriad of diseases. In this review, we provide a historical perspective, delve into folate chemistry that is often overlooked, and point out various missing links and underdeveloped areas in folate metabolism for future exploration.

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Figures

Figure 1.
Figure 1.
Folate chemistry. (A) Chemical structure of THF. (B) Redox reactions for the pteridine ring of folates. (C) The 1C unit is derived from donors such as serine, exists in three different oxidation states, and is used for various biochemical processes.
Figure 2.
Figure 2.
Folate decomposition and damage repair. (A) Chemical pathway of THF decomposition. (B) Cellular enzymatic systems for folate damage repair.
Figure 3.
Figure 3.
Folate transport and metabolic compartmentation. (A) Knowledge gaps in cellular folate metabolism. (B) Parallel cytosolic and mitochondrial folate pathways.
Figure 4.
Figure 4.
The folate cycle is linked to the methionine cycle via MTHFR and vitamin B12–using MTR.
See this image and copyright information in PMC

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References

    1. Anderson D.D., Quintero C.M., and Stover P.J.. 2011. Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc. Natl. Acad. Sci. USA. 108:15163–15168. 10.1073/pnas.1103623108 - DOI - PMC - PubMed
    1. Armengod M.E., Moukadiri I., Prado S., Ruiz-Partida R., Benítez-Páez A., Villarroya M., Lomas R., Garzón M.J., Martínez-Zamora A., Meseguer S., and Navarro-González C.. 2012. Enzymology of tRNA modification in the bacterial MnmEG pathway. Biochimie. 94:1510–1520. 10.1016/j.biochi.2012.02.019 - DOI - PubMed
    1. Bafunno V., Giancaspero T.A., Brizio C., Bufano D., Passarella S., Boles E., and Barile M.. 2004. Riboflavin uptake and FAD synthesis in Saccharomyces cerevisiae mitochondria: involvement of the Flx1p carrier in FAD export. J. Biol. Chem. 279:95–102. 10.1074/jbc.M308230200 - DOI - PubMed
    1. Baggott J.E. 2000. Hydrolysis of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate at pH 2.5 to 4.5. Biochemistry. 39:14647–14653. 10.1021/bi001362m - DOI - PubMed
    1. Baggott J.E., Johanning G.L., Branham K.E., Prince C.W., Morgan S.L., Eto I., and Vaughn W.H.. 1995. Cofactor role for 10-formyldihydrofolic acid. Biochem. J. 308:1031–1036. 10.1042/bj3081031 - DOI - PMC - PubMed

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