Overflow metabolism refers to the seemingly wasteful strategy in which cells incompletely oxidize their growth substrate (e.g.

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

) instead of using the respiratory pathway, even in the presence of oxygen. As a result of employing this metabolic strategy, cells excrete (or "overflow") metabolites like lactate,

acetate An acetate is a salt (chemistry), salt formed by the combination of acetic acid with a base (e.g. Alkali metal, alkaline, Alkaline earth metal, earthy, Transition metal, metallic, nonmetallic or radical Radical (chemistry), base). "Acetate" als ...

and

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

. Incomplete oxidation of growth substrates yields less energy (e.g. ATP) than complete oxidation through

respiration Respiration may refer to: Biology * Cellular respiration, the process in which nutrients are converted into useful energy in a cell ** Anaerobic respiration, cellular respiration without oxygen ** Maintenance respiration, the amount of cellula ...

, and yet overflow metabolism—known as the Warburg effect in the context of cancer and the

Crabtree effect The Crabtree effect, named after the English biochemist Herbert Grace Crabtree, describes the phenomenon whereby the yeast, ''Saccharomyces cerevisiae'', produces ethanol (alcohol) in aerobic conditions at high external glucose concentrations rath ...

in the context of yeast—occurs ubiquitously among fast-growing cells, including bacteria, fungi and mammalian cells. Based on experimental studies of acetate overflow in

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

, recent research has offered a general explanation for the association of overflow metabolism with fast growth. According to this theory, the enzymes required for respiration are more costly than those required for partial oxidation of glucose. That is, if the cell were to produce enough of these enzymes to support fast growth with respiratory metabolism, it would consume much more energy, carbon and nitrogen (per unit time) than supporting fast growth with an incompletely oxidative metabolism (e.g. fermentation). Given that cells have limited energy resources and fixed physical volume for proteins, there is thought to be a

trade-off A trade-off (or tradeoff) is a situational decision that involves diminishing or losing one quality, quantity, or property of a set or design in return for gains in other aspects. In simple terms, a tradeoff is where one thing increases, and anot ...

between efficient energy capture through central metabolism (i.e. respiration) and fast growth achieved through high central-metabolic fluxes (e.g. through fermentation as in

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...

). As an alternative explanation, it was suggested that cells could be limited by the rate with which they can dissipate

Gibbs energy In thermodynamics, the Gibbs free energy (or Gibbs energy; symbol G) is a thermodynamic potential that can be used to calculate the maximum amount of work (physics), work that may be performed by a closed system, thermodynamically closed system a ...

to the environment. Using combined thermodynamic and stoichiometric metabolic models in flux balance analyses with (i) growth maximization as objective function and (ii) an identified limit in the cellular

dissipation rate, correct predictions of physiological parameters, intracellular metabolic fluxes and metabolite concentrations were achieved.

References

{{Metabolism Metabolism

See also

References