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22 Dehydrogenases

(Balber, 2011).

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subject will guide future studies.

Adil M. Allahverdiyev, Malahat Bagirova, Olga Nehir Oztel, Serkan Yaman, Emrah Sefik Abamor, Rabia Cakir Koc,

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**Author details** 

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On the other hand, studies showed that BM ALDHbr populations may be useful in several cell therapy applications (Gentry*, et al.*, 2007). It is suggested that ALDHbr population may play an important role in regenerative medicine owing to Ras, which are one of the ALDH products. Paracrine effects of products of ALDH activity may influence tissue repair by binding to transcription factors and regulating developmental programs (Balber, 2011).

Therefore, regenerative potential of ALDHbr SCs were investigated in various disease models such as ischemic tissue damage hind limb model, brain damage and pancreatitis

Studies on ALDHbr cells provide restoration of tissue perfusion and stimulation of formation of new blood vessels in ischemic tissue damage (Keller, 2009). These promising findings showed that ALDHbr cells may gain importance in different areas; however, there are still many things to investigate about potential properties of ALDHbr cells for use in regenerative medicine. Thus, ALDH have many roles such as a marker of many disease and cell lines for detection of them also can using for therapy and have potential for use in regenerative

However, there are few studies about ALDH as a marker of SCs and potential usage in regenerative medicine. Therefore, we suggested that studies should focus on this and this review aims to consider the roles of ALDH in SCs and their potential use in regenerative medicine. We believe that constructing a review including current studies related to this

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**Chapter 2** 

© 2012 Friday et al., 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.

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,

**Role of Glutamate Dehydrogenase in Cancer** 

Ellen Friday, Robert Oliver III, Francesco Turturro and Tomas Welbourne

Glutamate Dehydrogenase (GDH) catalyzes the oxidative conversion of glutamate to alpha ketoglutarate and ammonium supplying the TCA cycle with intermediates in support of anaplerosis (**Figure 1 Rxn1**). Conversely GDH catalyzes the reductive amination of alpha ketoglutarate and ammonium producing glutamate when the TCA cycle pool is filled. The net GDH flux resulting from these bidirectional fluxes can be obtained from the conversion of either 15N labeled glutamate and analyzing 15N ammonium or from 15N labeled NH4+ and monitoring 15N labeled glutamate. Besides deamination and 15N NH4+ production*,* 15N labeled glutamate can be converted to 15N labeled amino acids, most prominently alanine, via transamination reactions (**Figure 1, Rxn2**). In contrast to glutamate deamination which yields net keto acid production for anaplerosis [1], transamination does not yield net keto acid production (consuming a keto acid e.g. pyruvate in the process of generating alpha ketoglutarate). Under physiological conditions plasma glutamate concentration, 10-20uM, is limiting for GDH flux supplying TCA intermediates while plasma glutamine concentration, 600uM, is not [2]. The conversion of 15N amide labeled glutamine to 15N ammonium (**Figure1, Rxn1**) approximates the net glutaminase flux generating glutamate and ammonium, both potential substrates for GDH. Indeed GDH can also incorporate the amide derived 15N ammonium and alpha ketoglutarate into glutamate (**Figure 1, Rxn3**, reductive amination) which can subsequently transaminate with pyruvate generating 15N alanine [3]. Noteworthy this glutaminolytic anabolic pathway providing glutamate has been proposed as the primary metabolic transformation in tumor cells [4]. **Figure 1, Rxn 3** also illustrates how ammonium production from the 15N amide of glutamine may underestimate the true glutaminase flux; to the extent that this occurs, it contributes to differences in estimated net glutaminase fluxes between the chemically measured glutamine disappearance and 15N amide ammonium appearance. Glutamine labeled with 15N in the amino position provides

**Growth and Homeostasis** 

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/48606

**1. Introduction** 

