Mathematical models for explaining the Warburg effect: a review focussed on ATP and biomass production. (27th November 2015)

• Record Type: Journal Article
• Authors: Schuster, Stefan; Boley, Daniel; Möller, Philip; Stark, Heiko; Kaleta, Christoph
• Is Part Of: Biochemical Society transactions. Volume 43:Number 6(2015)
• Page Start: 1187
• Page End: 1194
• Publication Date: 2015-11-27
• Subjects: cancer metabolism -- metabolic modelling -- rate vs. yield -- respirofermentation -- Warburg effect; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20150153
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : For producing ATP, tumour cells rely on glycolysis leading to lactate to about the same extent as on respiration. Thus, the ATP synthesis flux from glycolysis is considerably higher than in the corresponding healthy cells. This is known as the Warburg effect (named after German biochemist Otto H. Warburg) and also applies to striated muscle cells, activated lymphocytes, microglia, endothelial cells and several other cell types. For similar phenomena in several yeasts and many bacteria, the terms Crabtree effect and overflow metabolism respectively, are used. The Warburg effect is paradoxical at first sight because the molar ATP yield of glycolysis is much lower than that of respiration. Although a straightforward explanation is that glycolysis allows a higher ATP production rate, the question arises why cells do not re-allocate protein to the high-yield pathway of respiration. Mathematical modelling can help explain this phenomenon. Here, we review several models at various scales proposed in the literature for explaining the Warburg effect. These models support the hypothesis that glycolysis allows for a higher proliferation rate due to increased ATP production and precursor supply rates.