Identification of a Novel Activator of Mammalian Glutamate Dehydrogenase

Hong Q. Smith, Thomas J. Smith

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of l-glutamate and in animals is highly regulated. GDH in hyperinsulinism/hyperammonemia syndrome patients lacks GTP inhibition, resulting in hypersecretion of insulin upon protein consumption. This suggests insulin secretion could be stimulated with GDH activators. A high-throughput screen yielded one potent activator, N1-[4-(2-aminopyrimidin-4-yl)phenyl]-3-(trifluoromethyl)benzene-1-sulfonamide (75-E10). 75-E10 is ∼1000-fold more efficacious than the synthetic activator, BCH, and is at least as effective as ADP. 75-E10 compound is highly effective at alleviating GTP inhibition and may be binding to the ADP site. Unlike ADP, 75-E10 is activated over a broad range of conditions.

Original languageEnglish (US)
Pages (from-to)6568-6576
Number of pages9
Issue number47
StatePublished - Nov 29 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


Dive into the research topics of 'Identification of a Novel Activator of Mammalian Glutamate Dehydrogenase'. Together they form a unique fingerprint.

Cite this