Folate-mediated one-carbon metabolism.
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.
Fox
Jennifer T
JT
Graduate Field of Biochemistry, Molecular and Cellular Biology, Cornell University, Ithaca, New York 14853, USA.
Stover
Patrick J
PJ
D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology*; D003593:Cytoplasm / Q000201:enzymology*; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D008322:Mammals / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology*; D019875:One-Carbon Group Transferases / Q000378:metabolism*
D005492:Folic Acid; D019875:One-Carbon Group Transferases