Crystallographic structure of dimeric protein-glutaminase from Chryseobacterium proteolyticum.[1]
EC number
CAS number 9001-47-2
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
probable glutaminase from bacillus subtilis complexed with 6-diazo-5-oxo-l-norleucine
Symbol Glutaminase
Pfam PF04960
Pfam clan CL0013
InterPro IPR015868
SCOP 1mki

Glutaminase (EC, glutaminase I, L-glutaminase, glutamine aminohydrolase) is an amidohydrolase enzyme that generates glutamate from glutamine. Glutaminase has tissue-specific isoenzymes. Glutaminase has an important role in glial cells.

Glutaminase catalyzes the following reaction:

Glutamine + H2O → Glutamate + NH3


  • Tissue distribution 1
  • Regulation 2
  • Structure 3
  • Isozymes 4
  • Related proteins 5
  • References 6
  • External links 7

Tissue distribution

Glutaminase is expressed and active in periportal hepatocytes, where it generates NH3 (ammonia) for urea synthesis, as does glutamate dehydrogenase.[2] Glutaminase is also expressed in the epithelial cells of the renal tubules, where the produced ammonia is excreted as ammonium ions. This excretion of ammonium ions is an important mechanism of renal acid-base regulation. During chronic acidosis, glutaminase is induced in the kidney, which leads to an increase in the amount of ammonium ions excreted. Glutaminase can also be found in the intestines, whereby hepatic portal ammonia can reach as high as 0.26 mM (compared to an arterial blood ammonia of 0.02 mM).

One of the most important roles of glutaminase is found in the axonal terminals of neurons in the central nervous system. Glutamate is the most abundantly used excitatory neurotransmitter in the CNS. After being released into the synapse for neurotransmission, glutamate is rapidly taken up by nearby astrocytes, which convert it to glutamine. This glutamine is then supplied to the presynaptic terminals of the neurons, where glutaminases convert it back to glutamate for loading into synaptic vesicles. Although both "kidney-type" (GLS1) and "liver-type" (GLS2) glutaminases are expressed in brain, GLS2 has been reported to exist only in cellular nuclei in CNS neurons.[3]


ADP is the strongest adenine nucleotide activator of glutaminase. Studies have also suggested ADP lowered the K(m) for glutamine and increased the V(max). They found that these effects were increased even more when ATP was present.[4]

Phosphate-activated mitochondrial glutaminase (GLS2) is suggested to be linked with elevated metabolism, decreased intracellular reactive oxygen species (ROS) levels, and overall decreased DNA oxidation in both normal and stressed cells. It is suggested that GLS2’s control of ROS levels facilitates “the ability of p53 to protect cells from accumulation of genomic damage and allows cells to survive after mild and repairable genotoxic stress.”[5]


The structure of Glutaminase was determined using X-ray diffraction. The resolution of this protein is 1.73 Å. Resolution measures the quality of the data that has been collected on the crystal containing the protein. There are 2 chains containing 305 residues that make up the length of this dimeric protein. On each strand, 23% of Glutaminase, or 71 residues, are found in the 8 helices. Twenty-one percent, or 95 residues, construct the 23 beta sheet strands.[1]


Humans express 4 isoforms of glutaminase. GLS1 encodes 2 types of kidney-type glutaminase with a high activity and low Km. GLS2 encodes 2 forms of liver-type glutaminase with a low activity and allosteric regulation.[6]
Symbol GLS1
Entrez 2744
HUGO 4331
OMIM 138280
RefSeq NM_014905
UniProt O94925
Other data
EC number
Locus Chr. 2 q32-q34
glutaminase 2
(liver, mitochondrial)
Symbol GLS2
Entrez 27165
HUGO 29570
OMIM 606365
RefSeq NM_013267
UniProt Q9UI32
Other data
EC number
Locus Chr. 12 q13

Related proteins

Glutaminases belong to a larger family that includes serine-dependent beta-lactamases and penicillin-binding proteins. Many bacteria have two isozymes. This model is based on selected known glutaminases and their homologs within prokaryotes, with the exclusion of highly-derived (long-branch) and architecturally varied homologs, so as to achieve conservative assignments. A sharp drop in scores occurs below 250, and cutoffs are set accordingly. The enzyme converts glutamine to glutamate, with the release of ammonia. Members tend to be described as glutaminase A (glsA), where B (glsB) is unknown and may not be homologous (as in Rhizobium etli; some species have two isozymes that may both be designated A (GlsA1 and GlsA2).


  1. ^ a b  
  2. ^ Van Noorden, Botman (August 2014). "Determination of Phosphate-activated Glutaminase Activity and Its Kinetics in Mouse Tissues using Metabolic Mapping (Quantitative Enzyme Histochemistry)". Journal of Histochemistry & Cytochemistry.  
  3. ^ Olalla L, Gutiérrez A, Campos JA, Khan ZU, Alonso FJ, Segura JA, Márquez J, Aledo JC (Aug 2002). "Nuclear localization of L-type glutaminase in mammalian brain". J. Biol. Chem. 277 (41): 38939–38944.  
  4. ^ Masola B, Ngubane NP (December 2010). "The activity of phosphate-dependent glutaminase from the rat small intestine is modulated by ADP and is dependent on integrity of mitochondria". Arch. Biochem. Biophys. 504 (2): 197–203.  
  5. ^ Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S, Lokshin M, Hosokawa H, Nakayama T, Suzuki Y, Sugano S, Sato E, Nagao T, Yokote K, Tatsuno I, Prives C (April 2010). "Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species". Proc. Natl. Acad. Sci. U.S.A. 107 (16): 7461–6.  
  6. ^ Van Noorden, Botman (August 2014). "Determination of Phosphate-activated Glutaminase Activity and Its Kinetics in Mouse Tissues using Metabolic Mapping (Quantitative Enzyme Histochemistry)". Journal of Histochemistry & Cytochemistry.  

External links

  • Glutaminase at the US National Library of Medicine Medical Subject Headings (MeSH)
  • Research information on glutaminase (WikiGenes)