Evolved resistance to partial GAPDH inhibition results in loss of the Warburg effect and in a different state of glycolysis
| Autor: | Zufeng Guo, Jun O. Liu, Jason W. Locasale, Maria V. Liberti, Katherine R. Singleton, Kris C. Wood, Ziwei Dai, Vijyendra Ramesh, Annamarie E. Allen |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Dehydrogenase Oxidative phosphorylation Carbohydrate metabolism Biochemistry 03 medical and health sciences chemistry.chemical_compound Humans Glycolysis Enzyme Inhibitors Molecular Biology Glyceraldehyde 3-phosphate dehydrogenase 030102 biochemistry & molecular biology biology Fatty acid metabolism Chemistry Fatty Acids Cell Biology Warburg effect Oxygen Glucose Metabolism 030104 developmental biology Anaerobic glycolysis MCF-7 Cells biology.protein Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) Sesquiterpenes |
| Zdroj: | J Biol Chem |
| ISSN: | 0021-9258 |
| Popis: | Aerobic glycolysis or the Warburg effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although the WE is ubiquitous, its biological role remains controversial, and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, here we evolved resistance to koningic acid (KA), a natural product that specifically inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme, during the WE. We found that KA-resistant cells lose the WE but continue to conduct glycolysis and surprisingly remain dependent on glucose as a carbon source and also on central carbon metabolism. Consequently, this altered state of glycolysis led to differential metabolic activity and requirements, including emergent activities in and dependences on fatty acid metabolism. These findings reveal that aerobic glycolysis is a process functionally distinct from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions. |
| Databáze: | OpenAIRE |
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