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Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism.

Rui B, Yi Y, Shen T, Zheng M, Zhou W, Du H, Fan Y, Wang Y, Zhang Z, Xu S, Liu Z, Wen H, Xie X - PLoS ONE (2015)

Bottom Line: The clustering results were used to study the relationship between the flux of total NADPH regeneration and the flux in each NADPH producing enzyme.The results identified several reaction combinations supporting high NADPH regeneration, which are proven to be feasible in cells via thermodynamic analysis and coincident with a great deal of previous experimental report.These findings suggested cyclization pathways as a powerful way for NADPH regeneration capacity of bacterial central carbon metabolism.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science, Anhui Agricultural University, Hefei, China.

ABSTRACT
NADPH regeneration capacity is attracting growing research attention due to its important role in resisting oxidative stress. Besides, NADPH availability has been regarded as a limiting factor in production of industrially valuable compounds. The central carbon metabolism carries the carbon skeleton flux supporting the operation of NADPH-regenerating enzyme and offers flexibility in coping with NADPH demand for varied intracellular environment. To acquire an insightful understanding of its NADPH regeneration capacity, the elementary mode method was employed to compute all elementary flux modes (EFMs) of a network representative of central carbon metabolism. Based on the metabolic flux distributions of these modes, a cluster analysis of EFMs with high NADPH regeneration rate was conducted using the self-organizing map clustering algorithm. The clustering results were used to study the relationship between the flux of total NADPH regeneration and the flux in each NADPH producing enzyme. The results identified several reaction combinations supporting high NADPH regeneration, which are proven to be feasible in cells via thermodynamic analysis and coincident with a great deal of previous experimental report. Meanwhile, the reaction combinations showed some common characteristics: there were one or two decarboxylation oxidation reactions in the combinations that produced NADPH and the combination constitution included certain gluconeogenesis pathways. These findings suggested cyclization pathways as a powerful way for NADPH regeneration capacity of bacterial central carbon metabolism.

No MeSH data available.


Gibbs free energy of four flux modes.The horizontal coordinates are mode categories, and the longitudinal coordinates are the Gibbs free energy obtained by the Group Contribution Method. The top end of the red bar chart is the highest possible Gibbs free energy, and the bottom end is the lowest possible Gibbs free energy, while the black crosses represent Gibbs free energy obtained from the concentration of intracellular metabolites without oxidative stress.
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pone.0129837.g005: Gibbs free energy of four flux modes.The horizontal coordinates are mode categories, and the longitudinal coordinates are the Gibbs free energy obtained by the Group Contribution Method. The top end of the red bar chart is the highest possible Gibbs free energy, and the bottom end is the lowest possible Gibbs free energy, while the black crosses represent Gibbs free energy obtained from the concentration of intracellular metabolites without oxidative stress.

Mentions: Then, the normal ⊿rGm’, highest possible ⊿rGm’, and lowest possible ⊿rGm’ were computed, with the results shown in Fig 5. The black cross symbol in the bar middle represents normal ⊿rGm’, the top end of the bar chart is the highest possible ⊿rGm’, and the bottom end is the lowest possible ⊿rGm’. For the PP-EMP cycle, the values were -40.9, -10.3, and -71.5 kCal/mol, respectively. For the PP-ED-EMP cycle 1, the values were 2.34, 15.6, and -53.0 kCal/mol. For the PP-ED-EMP cycle 2, they were -22.1, 0.144, and -46.9kCal/mol. For the ME-PPC cycle, they were -2.32, 14.5, and -27.8kCal/mol. The physiological⊿rGm’s of ME-GLX and ME-TCA cycle are both less than zero. From the thermodynamic values, it can be seen that the PP-EMP cycle, PP-ED-EMP cycle 2 and ME related cycles are physiologically preferred and can happen under natural physiological condition. The lowest possible ⊿rGm’ of the PP-ED-EMP cycle 1 was significantly less than zero, while the activity of metabolites changed while super-oxidative stress occurred[35]. This could probably induce the operation of the PP-ED-EMP cycle 1.


Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism.

Rui B, Yi Y, Shen T, Zheng M, Zhou W, Du H, Fan Y, Wang Y, Zhang Z, Xu S, Liu Z, Wen H, Xie X - PLoS ONE (2015)

Gibbs free energy of four flux modes.The horizontal coordinates are mode categories, and the longitudinal coordinates are the Gibbs free energy obtained by the Group Contribution Method. The top end of the red bar chart is the highest possible Gibbs free energy, and the bottom end is the lowest possible Gibbs free energy, while the black crosses represent Gibbs free energy obtained from the concentration of intracellular metabolites without oxidative stress.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4472234&req=5

pone.0129837.g005: Gibbs free energy of four flux modes.The horizontal coordinates are mode categories, and the longitudinal coordinates are the Gibbs free energy obtained by the Group Contribution Method. The top end of the red bar chart is the highest possible Gibbs free energy, and the bottom end is the lowest possible Gibbs free energy, while the black crosses represent Gibbs free energy obtained from the concentration of intracellular metabolites without oxidative stress.
Mentions: Then, the normal ⊿rGm’, highest possible ⊿rGm’, and lowest possible ⊿rGm’ were computed, with the results shown in Fig 5. The black cross symbol in the bar middle represents normal ⊿rGm’, the top end of the bar chart is the highest possible ⊿rGm’, and the bottom end is the lowest possible ⊿rGm’. For the PP-EMP cycle, the values were -40.9, -10.3, and -71.5 kCal/mol, respectively. For the PP-ED-EMP cycle 1, the values were 2.34, 15.6, and -53.0 kCal/mol. For the PP-ED-EMP cycle 2, they were -22.1, 0.144, and -46.9kCal/mol. For the ME-PPC cycle, they were -2.32, 14.5, and -27.8kCal/mol. The physiological⊿rGm’s of ME-GLX and ME-TCA cycle are both less than zero. From the thermodynamic values, it can be seen that the PP-EMP cycle, PP-ED-EMP cycle 2 and ME related cycles are physiologically preferred and can happen under natural physiological condition. The lowest possible ⊿rGm’ of the PP-ED-EMP cycle 1 was significantly less than zero, while the activity of metabolites changed while super-oxidative stress occurred[35]. This could probably induce the operation of the PP-ED-EMP cycle 1.

Bottom Line: The clustering results were used to study the relationship between the flux of total NADPH regeneration and the flux in each NADPH producing enzyme.The results identified several reaction combinations supporting high NADPH regeneration, which are proven to be feasible in cells via thermodynamic analysis and coincident with a great deal of previous experimental report.These findings suggested cyclization pathways as a powerful way for NADPH regeneration capacity of bacterial central carbon metabolism.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science, Anhui Agricultural University, Hefei, China.

ABSTRACT
NADPH regeneration capacity is attracting growing research attention due to its important role in resisting oxidative stress. Besides, NADPH availability has been regarded as a limiting factor in production of industrially valuable compounds. The central carbon metabolism carries the carbon skeleton flux supporting the operation of NADPH-regenerating enzyme and offers flexibility in coping with NADPH demand for varied intracellular environment. To acquire an insightful understanding of its NADPH regeneration capacity, the elementary mode method was employed to compute all elementary flux modes (EFMs) of a network representative of central carbon metabolism. Based on the metabolic flux distributions of these modes, a cluster analysis of EFMs with high NADPH regeneration rate was conducted using the self-organizing map clustering algorithm. The clustering results were used to study the relationship between the flux of total NADPH regeneration and the flux in each NADPH producing enzyme. The results identified several reaction combinations supporting high NADPH regeneration, which are proven to be feasible in cells via thermodynamic analysis and coincident with a great deal of previous experimental report. Meanwhile, the reaction combinations showed some common characteristics: there were one or two decarboxylation oxidation reactions in the combinations that produced NADPH and the combination constitution included certain gluconeogenesis pathways. These findings suggested cyclization pathways as a powerful way for NADPH regeneration capacity of bacterial central carbon metabolism.

No MeSH data available.