The structure and allosteric regulation of glutamate dehydrogenase

Ming Li, Changhong Li, Aron Allen, Charles A. Stanley, Thomas J. Smith

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations


Glutamate dehydrogenase (GDH) has been extensively studied for more than 50 years. Of particular interest is the fact that, while considered by most to be a 'housekeeping' enzyme, the animal form of GDH is heavily regulated by a wide array of allosteric effectors and exhibits extensive inter-subunit communication. While the chemical mechanism for GDH has remained unchanged through epochs of evolution, it was not clear how or why animals needed to evolve such a finely tuned form of this enzyme. As reviewed here, recent studies have begun to elucidate these issues. Allosteric regulation first appears in the Ciliates and may have arisen to accommodate evolutionary changes in organelle function. The occurrence of allosteric regulation appears to be coincident with the formation of an 'antenna' like feature rising off the tops of the subunits that may be necessary to facilitate regulation. In animals, this regulation further evolved as GDH became integrated into a number of other regulatory pathways. In particular, mutations in GDH that abrogate GTP inhibition result in dangerously high serum levels of insulin and ammonium. Therefore, allosteric regulation of GDH plays an important role in insulin homeostasis. Finally, several compounds have been identified that block GDH-mediated insulin secretion that may be to not only find use in treating these insulin disorders but to kill tumors that require glutamine metabolism for cellular energy.

Original languageEnglish (US)
Pages (from-to)445-455
Number of pages11
JournalNeurochemistry International
Issue number4
StatePublished - Sep 2011
Externally publishedYes


  • Allostery
  • Glutamate dehydrogenase
  • Hyperinsulinism
  • Insulin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology


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