Macromolecular crowding explains overflow metabolism in cells

Alexei Vazquez, Zoltán N. Oltvai

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Overflow metabolism is a metabolic phenotype of cells characterized by mixed oxidative phosphorylation (OxPhos) and fermentative glycolysis in the presence of oxygen. Recently, it was proposed that a combination of a protein allocation constraint and a higher proteome fraction cost of energy generation by OxPhos relative to fermentation form the basis of overflow metabolism in the bacterium, Escherichia coli. However, we argue that the existence of a maximum or optimal macromolecular density is another essential requirement. Here we re-evaluate our previous theory of overflow metabolism based on molecular crowding following the proteomic fractions formulation. We show that molecular crowding is a key factor in explaining the switch from OxPhos to overflow metabolism.

Original languageEnglish (US)
Article number31007
JournalScientific reports
StatePublished - Aug 3 2016
Externally publishedYes


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