Journal of Bioenergetics and Biomembranes

, Volume 39, Issue 3, pp 223–229

Hypoxia, glucose metabolism and the Warburg’s effect

Authors

    • Unitat Bioquímica i Biologia Molecular, Departament de Ciències FisiològiquesCampus de Ciències de la Salut, IDIBELL – Universitat de Barcelona
    • Unitat Bioquímica i Biologia MolecularUniversitat de Barcelona
  • Jaime Caro
    • Cardeza FoundationThomas Jefferson University
    • Department of MedicineThomas Jefferson University
Mini Review

DOI: 10.1007/s10863-007-9080-3

Cite this article as:
Bartrons, R. & Caro, J. J Bioenerg Biomembr (2007) 39: 223. doi:10.1007/s10863-007-9080-3

Abstract

As described by Warburg more than 50 years ago, tumour cells maintain a high glycolytic rate even in conditions of adequate oxygen supply. However, most of tumours are subjected to hypoxic conditions due to the abnormal vasculature that supply them with oxygen and nutrients. Thus, glycolysis is essential for tumour survival and spread. A key step in controlling glycolytic rate is the conversion of fructose-6-P to fructose-1,6-P2 by 6-phosphofructo-1-kinase (PFK-1). The activity of PFK-1 is allosterically controlled by fructose-2,6-P2, the product of the enzymatic activity of a dual kinase/phosphatase family of enzymes (PFKFB1-4) that are increased in a significant number of tumour types. In turn, these enzymes are induced by hypoxia through the activation of the HIF-1 complex (hypoxia-inducible complex-1), a transcriptional activator that controls the expression of most of hypoxia-regulated genes. HIF-1 complex is overexpressed in a variety of tumours and its expression appears to correlate with poor prognosis and responses to chemo or radiotherapy. Thus, targeting PFKFB enzymes, either directly or through inhibition of HIF-1, appears as a promising approach for the treatment of certain tumours.

Keywords

HypoxiaGlucose metabolismWarburg’s effect

Copyright information

© Springer Science+Business Media, LLC 2007