Evidence for an Alternative Glycolytic Pathway in Rapidly Proliferating Cells

Author:

Vander Heiden Matthew G.123,Locasale Jason W.23,Swanson Kenneth D.2,Sharfi Hadar2,Heffron Greg J.4,Amador-Noguez Daniel5,Christofk Heather R.2,Wagner Gerhard4,Rabinowitz Joshua D.5,Asara John M.2,Cantley Lewis C.23

Affiliation:

1. Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

2. Beth Israel Deaconess Medical Center, Division of Signal Transduction and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

3. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

4. Department of Biological Chemistry and Molecular Pharmacology; Harvard Medical School, Boston, MA 02115, USA.

5. Lewis-Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.

Abstract

Glucose Metabolism Revisited 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, which has decreased activity? Vander Heiden et al. (p. 1492 ) 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 glycolyis.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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