Enzyme - Glutamate dehydrogenase

Alternative Name(s)
  • Glutamic dehydrogenase.

Catalytic Activity

H2O + L-glutamate + NAD(+) = 2-oxoglutarate + H(+) + NADH + NH4(+)


There are no Cofactors for this Enzyme

Reaction Mechanism

    Glutamate dehydrogenases catalyse the reversible oxidative deamination of L-glutamate, with NAD(P)H as cofactor. Glutamatc dehydrogcnases arc widely distributed throughout the cukaryotic, cubacterial and arc-haebaoterial kingdoms and these enzymes form a major link between protein and carbohydrate metabolism.

    The first step in the mechanism is the deprotonation of the alpha-amino group of the glutamate by Asp165, acting as general base, which occurs with subsequent hydride transfer to the Si face of the NAD+ and leads to the production of an iminoglutarate intermediate. The next step is the attack of a water molecule on the iminoglutarate intermediate is enhanced byLys125 acting as a general base via a hydrogen bond. During the generation of the carbinolamine intermediate and its subsequent collapse to the 2-oxoacid, Asp165 is crucial for the transfer of the proton to and from the substrate. Finally the loss of a proton from Lys125 and Asp165 ends the catalytic cycle.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    Lys P24295 126 1hrd 125
    Asp P24295 166 1hrd 165
    Step Components

    inferred reaction step, cofactor used, deamination, intermediate formation, hydride transfer, aromatic bimolecular nucleophilic addition, bimolecular nucleophilic addition, proton transfer, elimination (not covered by the Ingold mechanisms), overall reactant used, overall product formed

    Step 1.

    Asp165 acts as a general base to deprotonate the amine group of the substrate. This occurs with subsequent hydride transfer to the Si face of NAD+ and leads to the formation of an iminoglutamate intermediate.

    Step 2.

    Lys125 activates a water molecule for nucleophilic attack on the imine intermediate. Asp165 transfers a proton to the developing amine.

    Step 3.

    Asp165 abstracts a proton from the hydroxyl group of the carbinolamine intermediate. The intermediate collapses and ammonia is eliminated.

    Step 4.

    In an inferred step Asp165 and Lys125 are deprotonated to regenerate the active site.


    The products of the reaction.

Reaction Parameters

  • Kinetic Parameters
    Organism KM Value [mM] Substrate Comment
    Halobacterium salinarum 0.0018 L-glutamate pH 9.0, 40°C, recombinant enzyme in presence of DMSO
    [Clostridium] symbiosum 0.29 NAD+ mutant F232S/P262S/D263K , pH and temperature not specified in the publication
    Pyrobaculum calidifontis 3.2 L-glutamate pH 10.5, 50°C, recombinant enzyme
    Arabidopsis thaliana 5.22 L-glutamate with NAD+, recombinant enzyme, pH and temperature not specified in the publication
  • Temperature
    Organism Temperature Range Comment
    [Clostridium] symbiosum 8 - 37 decreasing temperature results in much lower enzyme activity
    Psychrobacter sp. 10 - 43 10°C: about 45% of maximal activity, 43°C: about 75% of maximal activity
    Peptoniphilus asaccharolyticus 40 - 80 40°C: about 50% of maximal activity, 80°C: about 40% of maximal activity
    Halobacterium salinarum 40 - 90 temperature profile, overview
  • pH
    Organism pH Range Comment
    Peptoniphilus asaccharolyticus 6 - 8
    Haloferax mediterranei 6.3 - 9.5
    Halobacterium salinarum 6.5 - 10.5 pH profile, overvew
    Bacillus subtilis 6.9 - 8
    Pisum sativum 7 - 8.8 about 50% of activity maximum at pH 7.0 and 8.8, reductive amination

Associated Proteins

Protein name Organism
Catabolic NAD-specific glutamate dehydrogenase RocG Bacillus subtilis (strain 168)
Probable NAD-specific glutamate dehydrogenase Fission yeast
NAD(+)-dependent glutamate dehydrogenase Pyrobaculum calidifontis (strain JCM 11548 / VA1)
Glutamate dehydrogenase 2 Slime mold
Cryptic catabolic NAD-specific glutamate dehydrogenase GudB Bacillus subtilis (strain 168)