Pathway Thermodynamics Highlights Kinetic Obstacles in Central Metabolism
Figure 3
MDF analysis of fermentation pathways.
(A) Structure of EMP-glycolysis. (B) Structure of an EMP pathway variant in which substrate-level phosphorylation is bypassed. The reactions marked in red are those with positive shadow prices at pH 7.5. Non-cofactor metabolites shaded in green show positive shadow prices. (C) MDF as function of pH, as calculated for the EMP pathway (cyan) and for an EMP pathway variant in which substrate-level phosphorylation is bypassed (magenta). ‘SLP’ corresponds to substrate-level phosphorylation. The Flux-Force Efficacy axis, on the right, refers to the reactions that dissipate the smallest amount of Gibbs energy, and hence equal to the pathway MDF. The light grey line marks the values corresponding to pH 7.5, the pH used in (D). (D) The MDF and ATP yield per glucose of the different fermentation pathways. ‘ED’ corresponds to the Entner-Doudoroff pathway. ‘EDSP’ represents the semi-phosphorylative ED pathway, known to operate in several hyperthermophilic archaea lineages [84], [88], [89]. ‘EDNP’ represents the non-phosphorylative ED pathway, also known to operate in hyperthermophilic archaea [84], [88], [89]. ‘MGX’ corresponds to a variant of the EMP pathway in which dihydroxyacetone phosphate is converted into the toxic compound methylglyoxal when the concentration of inorganic phosphate becomes limiting [85], [86], [87]. ‘PKT’ represents a pathway, suggested long ago [103], that uses the pentose phosphate pathway in conjunction with the enzyme phosphoketolase that cleaves xylulose-phosphate to glyceraldehyde-phosphate and acetyl-phosphate [90], [91]. ‘EMP PFL’ corresponds to a variant of the EMP pathway that produces more ATP by using the enzyme pyruvate formate lyase and performing substrate-level phosphorylation on of acetyl-phosphate. The structures of all pathways are given in Figure S2.