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Role of Glutamate Dehydrogenase in Cancer Growth and Homeostasis 39

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**Chapter 3** 

© 2012 Bingham and Zachar, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**The Pyruvate Dehydrogenase Complex in** 

**Cancer: Implications for the Transformed** 

The problem of finding effective chemotherapies for advanced cancer remains largely unsolved. We review here the role of a specific class of central metabolic dehydrogenases whose regulatory properties are remodeled significantly in cancer cells. These remodeled properties may provide an attractive set of targets for the development of new chemotherapeutic drugs. The design features of the first agents to be developed attacking these new targets [1,2] may

illustrate ways to exploit this potentially valuable therapeutic opportunity.

dependent mitochondrial electron transport system for ATP production [6].

**ketoglutarate (KDGH) complexes in cell metabolism** 

**2. The central role of the pyruvate dehydrogenase (PDH) and alpha-**

The evolution of the high-energy, oxygen-dependent metabolism of eukaryotes [4,5] has produced mitochondrial metabolic pathways whose control is centrally focused on a series of dehydrogenases. Two of these pivotal dehydrogenases, the pyruvate dehydrogenase (PDH) and alpha-ketoglutarate or 2-oxoglutarate (KDGH) complex will be our central focus here. These dehydrogenases control the entry of carbon into the TCA cycle from two major sources, carbohydrate and gluconeogenic amino acids (pyruvate; PDH) and glutamine (KGDH), the most abundant serum amino acid and a central carbon source for normal and pathological tissues (Figure 1). The TCA cycle, in turn, is almost exclusively responsible for the capture of reducing potential from nutrients for the purpose of driving the oxygen-

In the solid, three dimensional structure of animal bodies the availability of nutrients and molecular oxygen is locally contingent and dynamically variable. Thus, continuous real-time

and reproduction in any medium, provided the original work is properly cited.

**State and Cancer Chemotherapy** 

Paul M. Bingham and Zuzana Zachar

http://dx.doi.org/10.5772/48582

**1. Introduction** 

Additional information is available at the end of the chapter
