Journal of Bioenergetics and Biomembranes

, Volume 39, Issue 3, pp 223–229 | Cite as

Hypoxia, glucose metabolism and the Warburg’s effect

Mini Review

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

Hypoxia Glucose metabolism Warburg’s effect 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Unitat Bioquímica i Biologia Molecular, Departament de Ciències FisiològiquesCampus de Ciències de la Salut, IDIBELL – Universitat de BarcelonaBarcelonaSpain
  2. 2.Unitat Bioquímica i Biologia MolecularUniversitat de BarcelonaBarcelonaSpain
  3. 3.Cardeza FoundationThomas Jefferson UniversityPhiladelphiaUSA
  4. 4.Department of MedicineThomas Jefferson UniversityPhiladelphiaUSA

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