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Cell cycle regulation of folate‐mediated one‐carbon metabolism

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Folate‐mediated one‐carbon metabolism (FOCM) comprises a network of interconnected folate‐dependent metabolic pathways responsible for serine and glycine interconversion, de novo purine synthesis, de novo thymidylate synthesis and homocysteine remethylation to methionine. These pathways are compartmentalized in the cytosol, nucleus and mitochondria. Individual enzymes within the FOCM network compete for folate cofactors because intracellular folate concentrations are limiting. Although there are feedback mechanisms that regulate the partitioning of folate cofactors among the folate‐dependent pathways, less recognized is the impact of cell cycle regulation on FOCM. This review summarizes the evidence for temporal regulation of expression, activity and cellular localization of enzymes and pathways in the FOCM network in mammalian cells through the cell cycle. This article is categorized under: Biological Mechanisms > Metabolism Physiology > Mammalian Physiology in Health and Disease

Compartmentation of folate‐mediated one‐carbon metabolism. One‐carbon units in FOCM are derived from serine and histidine catabolism in the cytosol, and from the catabolism of serine, glycine and choline‐derived methyl‐glycine species in the mitochondria. FOCM in the cytoplasm is required for de novo purine synthesis, for de novo thymidylate synthesis and for homocysteine remethylation to methionine. FOCM in the nucleus is required for de novo thymidylate synthesis at sites of DNA replication. The de novo thymidylate synthesis pathway is also present in the mitochondria

[Correction added on 25 June 2018, after first online publication: Figure 1 has been updated to include missing labels in some of the gray boxes.]

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