%0 Journal Article
%T Redox balance is key to explaining full vs. partial switching to low-yield metabolism
%A Milan JA van Hoek
%A Roeland MH Merks
%J BMC Systems Biology
%D 2012
%I BioMed Central
%R 10.1186/1752-0509-6-22
%X Using flux balance analysis with molecular crowding (FBAwMC), a recent extension to flux balance analysis (FBA) that assumes that the total flux through the metabolic network is limited, we investigate the differences between Saccharomyces cerevisiae and L. lactis that downregulate the high-yield pathway at increasing glucose concentrations, and E. coli, which keeps the high-yield pathway functioning at maximal rate. FBAwMC correctly predicts the metabolic switching mode in these three organisms, suggesting that metabolic network architecture is responsible for differences in metabolic switching mode. Based on our analysis, we expect gradual, "overflow-like" switching behavior in organisms that have an additional energy-yielding pathway that does not consume NADH (e.g., acetate production in E. coli). Flux decrease through the high-yield pathway is expected in organisms in which the high-yield and low-yield pathways compete for NADH. In support of this analysis, a simplified model of metabolic switching suggests that the extra energy generated during acetate production produces an additional optimal growth mode that smoothens the metabolic switch in E. coli.Maintaining redox balance is key to explaining why some microbes decrease the flux through the high-yield pathway, while other microbes use "overflow-like" low-yield metabolism.One of the key steps in energy metabolism is to transfer the energy carried by sugars, including glucose, to the biological "energy currency" adenosine triphosphate (ATP). The number of ATP molecules generated by metabolizing one molecule of glucose¡ªthe ATP yield¡ªis one of the most basic measures of an organism's energy efficiency. One would perhaps expect that evolution has selected organisms for the ability to extract energy from their food at optimal efficiency by maximizing ATP yield. Yet surprisingly, many organisms switch between a high-yield pathway, e.g., aerobic respiration that yields more than thirty moles of ATP per mole glucos
%K Metabolic switching
%K Genome-scale metabolic model
%K Flux Balance Analysis with Molecular Crowding
%K Overflow metabolism
%K Redox balance
%K Escherichia coli
%K Lactococcus lactis
%K Saccharomyces cerevisiae
%U http://www.biomedcentral.com/1752-0509/6/22