PMID- 27484619 OWN - NLM STAT- MEDLINE DCOM- 20180424 LR - 20240210 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Aug 3 TI - Macromolecular crowding explains overflow metabolism in cells. PG - 31007 LID - 10.1038/srep31007 [doi] LID - 31007 AB - 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. FAU - Vazquez, Alexei AU - Vazquez A AD - Beatson Institute for Cancer Research, Glasgow, UK. FAU - Oltvai, Zoltan N AU - Oltvai ZN AD - Departments of Pathology and Computational &Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. LA - eng GR - 21140/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article DEP - 20160803 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 SB - IM MH - *Biobehavioral Sciences MH - Escherichia coli/*metabolism MH - Glycolysis/*physiology MH - *Oxidative Phosphorylation PMC - PMC4971534 EDAT- 2016/08/04 06:00 MHDA- 2018/04/25 06:00 PMCR- 2016/08/03 CRDT- 2016/08/04 06:00 PHST- 2016/04/20 00:00 [received] PHST- 2016/07/11 00:00 [accepted] PHST- 2016/08/04 06:00 [entrez] PHST- 2016/08/04 06:00 [pubmed] PHST- 2018/04/25 06:00 [medline] PHST- 2016/08/03 00:00 [pmc-release] AID - srep31007 [pii] AID - 10.1038/srep31007 [doi] PST - epublish SO - Sci Rep. 2016 Aug 3;6:31007. doi: 10.1038/srep31007.