Modeling cellular compartmentation in one-carbon metabolism

Wiley Interdiscip Rev Syst Biol Med. May-Jun 2013;5(3):343-65. doi: 10.1002/wsbm.1209. Epub 2013 Feb 13.

Abstract

Folate-mediated one-carbon metabolism (FOCM) is associated with risk for numerous pathological states including birth defects, cancers, and chronic diseases. Although the enzymes that constitute the biological pathways have been well described and their interdependency through the shared use of folate cofactors appreciated, the biological mechanisms underlying disease etiologies remain elusive. The FOCM network is highly sensitive to nutritional status of several B-vitamins and numerous penetrant gene variants that alter network outputs, but current computational approaches do not fully capture the dynamics and stochastic noise of the system. Combining the stochastic approach with a rule-based representation will help model the intrinsic noise displayed by FOCM, address the limited flexibility of standard simulation methods for coarse-graining the FOCM-associated biochemical processes, and manage the combinatorial complexity emerging from reactions within FOCM that would otherwise be intractable.

Publication types

  • Review

MeSH terms

  • Carbon / metabolism*
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Folic Acid / metabolism*
  • Homocysteine / metabolism
  • Methionine / metabolism
  • Mitochondria / metabolism
  • Models, Biological*
  • Purine Nucleosides / biosynthesis
  • Thymidine Monophosphate / biosynthesis

Substances

  • Purine Nucleosides
  • Homocysteine
  • Thymidine Monophosphate
  • Carbon
  • Folic Acid
  • Methionine