Folate-mediated one-carbon metabolism. Academic Article uri icon


  • Tetrahydrofolate (THF) polyglutamates are a family of cofactors that carry and chemically activate one-carbon units for biosynthesis. THF-mediated one-carbon metabolism is a metabolic network of interdependent biosynthetic pathways that is compartmentalized in the cytoplasm, mitochondria, and nucleus. One-carbon metabolism in the cytoplasm is required for the synthesis of purines and thymidylate and the remethylation of homocysteine to methionine. One-carbon metabolism in the mitochondria is required for the synthesis of formylated methionyl-tRNA; the catabolism of choline, purines, and histidine; and the interconversion of serine and glycine. Mitochondria are also the primary source of one-carbon units for cytoplasmic metabolism. Increasing evidence indicates that folate-dependent de novo thymidylate biosynthesis occurs in the nucleus of certain cell types. Disruption of folate-mediated one-carbon metabolism is associated with many pathologies and developmental anomalies, yet the biochemical mechanisms and causal metabolic pathways responsible for the initiation and/or progression of folate-associated pathologies have yet to be established. This chapter focuses on our current understanding of mammalian folate-mediated one-carbon metabolism, its cellular compartmentation, and knowledge gaps that limit our understanding of one-carbon metabolism and its regulation.

published proceedings

  • Vitam Horm

altmetric score

  • 0.25

author list (cited authors)

  • Fox, J. T., & Stover, P. J.

citation count

  • 286

complete list of authors

  • Fox, Jennifer T||Stover, Patrick J

publication date

  • January 2008