Glutamate dehydrogenase

glutamate dehydrogenase (GLDH)
Identifiers
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

glutamate dehydrogenase [NAD(P)+]
Identifiers
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

glutamate dehydrogenase (NADP+)
Identifiers
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

Glutamate dehydrogenase (GLDH, GDH) is an

${\displaystyle K_{m}}$ of about 1 mM), and therefore toxic levels of ammonia would have to be present in the body for the reverse reaction to proceed (that is, α-ketoglutarate and ammonia to glutamate and NAD(P)+). However, in brain, the NAD+/NADH ratio in brain mitochondria encourages oxidative deamination (i.e. glutamate to α-ketoglutarate and ammonia).^[1] In bacteria, the ammonia is assimilated to amino acids via glutamate and aminotransferases.^[2] In plants, the enzyme can work in either direction depending on environment and stress.^[3][4] Transgenic plants expressing microbial GLDHs are improved in tolerance to herbicide, water deficit, and pathogen infections.^[5] They are more nutritionally valuable.^[6]

The enzyme represents a key link between

as well, probably reflecting microbial influences on eukaryote evolution.

• 
  Glutamate
• 
  α-Ketoglutarate

Clinical application

GLDH can be measured in a

]

Enzyme immunoassay (EIA) for glutamate dehydrogenase (GDH) can be used as screening tool for patients with Clostridioides difficile infection. The enzyme is expressed constitutively by most strains of C.diff, and can thus be easily detected in stool. Diagnosis is generally confirmed with a follow-up EIA for C. Diff toxins A and B.^{[citation needed]}

Cofactors

Based on which cofactor is used, glutamate dehydrogenase enzymes are divided into the following three classes:^[citation needed]

• EC 1.4.1.2: L-glutamate + H₂O + NAD⁺ ${\displaystyle \rightleftharpoons }$ 2-oxoglutarate + NH₃ + NADH + H⁺
• EC 1.4.1.3: L-glutamate + H₂O + NAD(P)⁺ ${\displaystyle \rightleftharpoons }$ 2-oxoglutarate + NH₃ + NAD(P)H + H⁺
• EC 1.4.1.4: L-glutamate + H₂O + NADP⁺ ${\displaystyle \rightleftharpoons }$ 2-oxoglutarate + NH₃ + NADPH + H⁺

Role in flow of nitrogen

Ammonia incorporation in animals and microbes occurs through the actions of glutamate dehydrogenase and

]

Regulation of glutamate dehydrogenase

In humans, the activity of glutamate dehydrogenase is controlled through

]

In microbes, the activity is controlled by the concentration of ammonium and or the like-sized rubidium ion, which binds to an allosteric site on GLDH and changes the K_m (

The control of GLDH through ADP-ribosylation is particularly important in

levels.

Bovine liver glutamate dehydrogenase was found to be regulated by nucleotides in the late 1950s and early 1960s by Carl Frieden.[9] ^{[10] [11] [12]} In addition to describing the effects of nucleotides like ADP, ATP and GTP he described in detail the different kinetic behavior of NADH and NADPH. As such it was one of the earliest enzymes to show what was later described as allosteric behavior. ^[13]

The activation of mammalian GDH by L-leucine and some other hydrophobic amino acids has also been long known,^[14] however localization of the binding site was not clear. Only recently the new allosteric binding site for L-leucine was identified in a mammalian enzyme.^[15]

Mutations which alter the allosteric binding site of GTP cause permanent activation of glutamate dehydrogenase, and lead to hyperinsulinism-hyperammonemia syndrome.

Regulation

Allosteric regulation:

This protein may use the morpheein model of allosteric regulation.^[7][16]

Allosteric inhibitors:

• Guanosine triphosphate (GTP)
• Adenosine triphosphate (ATP)
• Palmitoyl-CoA
• Zn²⁺

Activators:

• Adenosine diphosphate (ADP) ^[15]
• Leucine^[15]
• l-isoleucine
• l-valine
• Guanosine diphosphate

Other Inhibitors:

• EGCG^[17]

Additionally, Mice GLDH shows substrate inhibition by which GLDH activity decreases at high glutamate concentrations.[7]

Isozymes

Humans express the following glutamate dehydrogenase isozymes:

Chr. 10 q21.1-24.3 Search for Structures Swiss-model Domains InterPro

Chr. X q25 Search for Structures Swiss-model Domains InterPro

See also

• Anaplerotic reactions

References

External links

• Glutamate+dehydrogenase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)