Identification of a Novel Activator of Mammalian Glutamate Dehydrogenase

Hong Q. Smith, Thomas Smith

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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
JournalBiochemistry
Volume55
Issue number47
DOIs
StatePublished - Nov 29 2016

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Glutamate Dehydrogenase
Adenosine Diphosphate
Guanosine Triphosphate
Insulin
Deamination
Sulfonamides
Benzene
Glutamic Acid
Animals
Throughput
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of a Novel Activator of Mammalian Glutamate Dehydrogenase. / Smith, Hong Q.; Smith, Thomas.

In: Biochemistry, Vol. 55, No. 47, 29.11.2016, p. 6568-6576.

Research output: Contribution to journalArticle

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