Neurochemical Research

, Volume 44, Issue 1, pp 117–132 | Cite as

Glutamate Dehydrogenase, a Complex Enzyme at a Crucial Metabolic Branch Point

  • Hong Q. Smith
  • Changhong Li
  • Charles A. Stanley
  • Thomas James SmithEmail author
Original Paper


In-vitro, glutamate dehydrogenase (GDH) catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate (α-KG). GDH is found in all organisms, but in animals is allosterically regulated by a wide array of metabolites. For many years, it was not at all clear why animals required such complex control. Further, in both standard textbooks and some research publications, there has been some controversy as to the directionality of the reaction. Here we review recent work demonstrating that GDH operates mainly in the catabolic direction in-vivo and that the finely tuned network of allosteric regulators allows GDH to meet the varied needs in a wide range of tissues in animals. Finally, we review the progress in using pharmacological agents to activate or inhibit GDH that could impact a wide range of pathologies from insulin disorders to tumor growth.


Glutamate dehydrogenase Allostery Insulin 



This work was supported by National Institutes of Health Grants 1RO1DK098517-01A1 and R01-DK098517-03S1 (C.L.), R37-DK056268 (C.A.S), and R01-DK072171 (T.J.S.).


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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Texas Medical Branch at GalvestonGalvestonUSA
  2. 2.Division of EndocrinologyThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA

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