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

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Abstract

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.

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Acknowledgements

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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  1. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, USA

    Hong Q. Smith & Thomas James Smith

  2. Division of Endocrinology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Changhong Li & Charles A. Stanley

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  1. Hong Q. Smith
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Correspondence to Thomas James Smith.

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Smith, H.Q., Li, C., Stanley, C.A. et al. Glutamate Dehydrogenase, a Complex Enzyme at a Crucial Metabolic Branch Point. Neurochem Res 44, 117–132 (2019). https://doi.org/10.1007/s11064-017-2428-0

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