Cell cycle regulation of folate‐mediated one‐carbon metabolism. (11th June 2018)

• Record Type: Journal Article
• Authors: Lan, Xu; Field, Martha S.; Stover, Patrick J.
• Is Part Of: Wiley interdisciplinary reviews. Volume 10:Number 6(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-06-11
• Subjects: cell cycle -- folate -- one‐carbon metabolism; Systems biology -- Periodicals; Medicine -- Periodicals; 610
• DOI: 10.1002/wsbm.1426
• Languages: English
• ISSNs: 1939-5094

Abstract

Abstract : 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 Abstract : Individual enzymes within the FOCM network compete for limited folate cofactors. Cell cycle regulated‐expression, activity and cellular localization of enzymes and pathways in FOCM network enable cells to prioritize individual pathways within the network according to temporal needs. De novo purine and dTMP biosynthesis are regulated by cell cycle through both an increase in enzyme activity and formation of multienzyme complexes. Enzymes in dTMP biosynthesis pathway translocate in the nucleus and form complexes at sites of DNA replication.