InterPro domain: IPR006097

Glutamate, leucine, phenylalanine and valine dehydrogenases are structurally and functionally related. They contain a Gly-rich region containing a conserved Lys residue, which has been implicated in the catalytic activity, in each case a reversible oxidative deamination reaction.

Glutamate dehydrogenases ( 1.4.1.2 , 1.4.1.3 , and 1.4.1.4 ) (GluDH) are enzymes that catalyse the NAD- and/or NADP-dependent reversible deamination of L-glutamate into alpha-ketoglutarate [ 1 , 2 ]. GluDH isozymes are generally involved with either ammonia assimilation or glutamate catabolism. Two separate enzymes are present in yeasts: the NADP-dependent enzyme, which catalyses the amination of alpha-ketoglutarate to L-glutamate; and the NAD-dependent enzyme, which catalyses the reverse reaction [ 3 ] - this form links the L-amino acids with the Krebs cycle, which provides a major pathway for metabolic interconversion of alpha-amino acids and alpha- keto acids [ 4 ]. In rice, glutamate dehydrogenase 3 is mitochondrial.

Leucine dehydrogenase ( 1.4.1.9 ) (LeuDH) is a NAD-dependent enzyme that catalyses the reversible deamination of leucine and several other aliphatic amino acids to their keto analogues [ 5 ]. Each subunit of this octameric enzyme from Bacillus sphaericus contains 364 amino acids and folds into two domains, separated by a deep cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft, which is thought to close during the hydride transfer step of the catalytic cycle.

Phenylalanine dehydrogenase ( 1.4.1.20 ) (PheDH) is na NAD-dependent enzyme that catalyses the reversible deamidation of L-phenylalanine into phenyl-pyruvate [ 6 ].

Valine dehydrogenase ( 1.4.1.8 ) (ValDH) is an NADP-dependent enzyme that catalyses the reversible deamidation of L-valine into 3-methyl-2-oxobutanoate [ 7 ].

This entry represents the dimerisation region of these enzymes.

1. Structural relationship between the hexameric and tetrameric family of glutamate dehydrogenases. Eur. J. Biochem. 209, 851-9
2. Evolution of glutamate dehydrogenase genes: evidence for two paralogous protein families and unusual branching patterns of the archaebacteria in the universal tree of life. J. Mol. Evol. 36, 335-46
3. Nucleotide sequence of yeast GDH1 encoding nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase. J. Biol. Chem. 260, 8502-8
4. Isolation and characterization of cDNA clones encoding human liver glutamate dehydrogenase: evidence for a small gene family. Proc. Natl. Acad. Sci. U.S.A. 85, 3494-8
5. Gene cloning and sequence determination of leucine dehydrogenase from Bacillus stearothermophilus and structural comparison with other NAD(P)+-dependent dehydrogenases. Biochemistry 27, 9056-62
6. Thermostable phenylalanine dehydrogenase of Thermoactinomyces intermedius: cloning, expression, and sequencing of its gene. J. Biochem. 109, 371-6
7. Sequence, transcriptional, and functional analyses of the valine (branched-chain amino acid) dehydrogenase gene of Streptomyces coelicolor. J. Bacteriol. 175, 4176-85