Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step

• DOI: 10.7554/elife.03342
• Publication Date: 2014-07-09T15:23:27Z
• Authors: Alexander A Shestov; Xiaojing Liu; Zheng Ser; Ahmad A Cluntun; Yin P Hung; Lei Huang; Dongsung Kim; Anne Le; Gary Yellen; John G Albeck; Jason W Locasale
• Keywords: Anaerobic glycolysis; Glyceraldehyde 3-phosphate dehydrogenase; Warburg Effect; Metabolic control analysis; Metabolic pathway

Aerobic glycolysis or the Warburg Effect (WE) is characterized by increased metabolism of glucose to lactate. It remains unknown what quantitative changes activity are necessary and sufficient for this phenotype. We developed a computational model an integrated analysis using metabolic control (MCA), metabolomics data, statistical simulations. identified confirmed novel mode regulation specific aerobic where flux through GAPDH, enzyme separating lower upper glycolysis, rate-limiting step in pathway levels fructose (1,6) bisphosphate (FBP), predictive rate points glycolysis. Strikingly, negative was found several steps thought be Together, these findings enumerate biochemical determinants WE suggest strategies identifying contexts which agents that target might most effective.