One-carbon metabolism in cancer cells: a critical review based on a core model of central metabolism

Biochem Soc Trans. 2021 Feb 26;49(1):1-15. doi: 10.1042/BST20190008.

Abstract

One-carbon metabolism (1C-metabolism), also called folate metabolism because the carbon group is attached to folate-derived tetrahydrofolate, is crucial in metabolism. It is at the heart of several essential syntheses, particularly those of purine and thymidylate. After a short reminder of the organization of 1C-metabolism, I list its salient features as reported in the literature. Then, using flux balance analysis, a core model of central metabolism and the flux constraints for an 'average cancer cell metabolism', I explore the fundamentals underlying 1C-metabolism and its relationships with the rest of metabolism. Some unreported properties of 1C-metabolism emerge, such as its potential roles in mitochondrial NADH exchange with cytosolic NADPH, participation in NADH recycling, and optimization of cell proliferation.

Keywords: average cancer cell; cancer cells’ metabolism; flux balance analysis; metabolic model; one-carbon metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biochemical Phenomena
  • Carbon / metabolism*
  • Energy Metabolism / physiology
  • Humans
  • Mitochondria / metabolism
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology

Substances

  • Carbon