Metabolic flux analysis
Metabolic flux analysis (MFA) is an experimental fluxomics technique used to examine production and consumption rates of metabolites in a biological system. At an intracellular level, it allows for the quantification of metabolites, thereby elucidating the central metabolism of the cell.[1] Employing stoichiometric models of metabolism and mass spectrometry methods with isotopic mass resolution, the transfer of moieties containing isotopic tracers from one metabolite into another can be elucidated, and information about the metabolic network thus derived. Metabolic flux analysis (MFA) has many applications such as determining the limits on the ability of a biological system in producing a biochemical such as ethanol[2] and predicting the response to gene additions or knockouts.[3][4]
Metabolic flux analysis may use 13C to determine pathway fluxes, NMR techniques and mass spectrometry.[5][1][6][7]
Thermodynamics-Based Metabolic Flux Analysis[4]
Thermodynamics-Based Metabolic Flux Analysis (TMFA) is a specialized type of metabolic flux analysis which utilizes linear thermodynamic constraints in addition to mass balance constraints to generate thermodynamically feasible fluxes and metabolite activity profiles. TMFA takes into consideration only pathways and fluxes that are feasible by using the Gibbs free energy change of the reactions and activities of the metabolites that are part of the model.[4]
See also
See Isotopic labeling for a brief treatment of stable isotope labeling.
References
- 13C metabolic flux analysis. Metab. Eng. 2001, 3(3), 195-206, Wiechert W
- Papoutsakis, Eleftherios Terry; Meyer, Charles L. (1985-01-01). "Equations and calculations of product yields and preferred pathways for butanediol and mixed-acid fermentations". Biotechnology and Bioengineering. 27 (1): 50–66. doi:10.1002/bit.260270108. ISSN 1097-0290. PMID 18553576. S2CID 41031084.
- Burgard, Anthony P.; Maranas, Costas D. (2001-09-05). "Probing the performance limits of the Escherichia coli metabolic network subject to gene additions or deletions". Biotechnology and Bioengineering. 74 (5): 364–375. doi:10.1002/bit.1127. ISSN 1097-0290. PMID 11427938. S2CID 15522589.
- Hatzimanikatis, Vassily; Broadbelt, Linda J.; Henry, Christopher S. (2007-03-01). "Thermodynamics-Based Metabolic Flux Analysis". Biophysical Journal. 92 (5): 1792–1805. Bibcode:2007BpJ....92.1792H. doi:10.1529/biophysj.106.093138. ISSN 0006-3495. PMC 1796839. PMID 17172310.
- 13C-based metabolic flux analysis, Nature Protocols 4, 878-892 (2009), Nicola Zamboni1, Sarah-Maria Fendt, Martin Rühl & Uwe Sauer
- Metabolic flux analysis of Escherichia coli K12 grown on 13C-labeled acetate and glucose using GC-MS and powerful flux calculation method. J Biotechnol. (2003) 101(2):101-17. Zhao J, Shimizu K.
- 13C metabolic flux analysis in complex systems. Curr Opin Biotechnol. 22(1):103-8 (2011) Zamboni N.