Glucose Metabolism Revisited

Science Signaling  21 Sep 2010:
Vol. 3, Issue 140, pp. ec289
DOI: 10.1126/scisignal.3140ec289

Cancer cells are revved up to reproduce rapidly and typically consume glucose rapidly by glycolysis. Why, then, do cancer cells express an isoform of a rate-limiting enzyme in glycolysis, pyruvate kinase M2, that has decreased activity? Vander Heiden et al. propose that consequent accumulation of phosphoenolpyruvate, with the help of an enzymatic activity that remains to be characterized, can lead to phosphate transfer to phosphoglycerate mutase, another glycolytic enzyme, providing the cell with a different way to make pyruvate. This may allow cancer cells to produce pyruvate without generating excess adenosine triphosphate, which can act through feedback to inhibit glycolysis.

M. G. Vander Heiden, J. W. Locasale, K. D. Swanson, H. Sharfi, G. J. Heffron, D. Amador-Noguez, H. R. Christofk, G. Wagner, J. D. Rabinowitz, J. M. Asara, L. C. Cantley, Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 329, 1492–1499 (2010). [Abstract] [Full Text]