Glutamate ammonium ligase

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Glutamate ammonium ligase
Glutamate ammonium ligase
Top and side views of the glutamate ammonium ligase

Existing structural data : 1f1h , 1f52 , 1fpy , 1hto , 1lgr , 2bvc , 2gls , 2qc8 , 2ojw

Properties of human protein
Secondary to quaternary structure Homotetramer, homooctamer
Identifier
Gene name GLUL
External IDs
Enzyme classification
EC, category 6.3.1.2 ligase
Substrate Glutamate + ATP + NH 4 +
Products ADP, phosphate, L- glutamine
Occurrence
Parent taxon Creature
Orthologue
human House mouse
Entrez 2752 14645
Ensemble ENSG00000135821 ENSMUSG00000026473
UniProt P15104 P15105
Refseq (mRNA) NM_001033044 NM_008131
Refseq (protein) NP_001028216 NP_032157
Gene locus Chr 1: 182.38 - 182.39 Mb Chr 1: 153.9 - 153.91 Mb
PubMed search 2752 14645

Glutamate ammonium ligase ( GS for short, from obsolete glutamine synthetase ) are called enzymes that transfer ammonium to the amino acid glutamate while consuming ATP . This creates the amino acid glutamine . They thus play an important role in the nitrogen metabolism of all living things, for example in the biosynthesis of glutamine, which in turn serves as a starting point for the synthesis of other compounds. In humans, GS assimilates toxic ammonium and occurs primarily in the brain, kidneys and liver. The ammonium transferred to glutamate in this way can be transferred to urea in the liver via the urea cycle and thus excreted via the kidneys. The human GS is also expressed during the early fetal phase, but nitrogen assimilation as in bacteria does not take place, since the glutamate synthase, which is essential for this, is not available in humans, and humans are therefore dependent on amino acid intake. Mutations in GLUL - gene can lead to very rare fetal systemic glutamine deficiency, which leads to severe damage and death of the newborn.

The GS is part of the so-called GS / GOGAT pathway (glutamine synthetase / glutamine oxoglutarate aminotransferase), an alternative way of assimilation of ammonia in addition to the reaction by glutamate dehydrogenase .

Classes

GS is a widely used enzyme, the various forms can be divided into three classes:

  • Class 1: This type is found exclusively in prokaryotes and consists of twelve identical subunits of 50 kDa each  . The enzyme is under the control of cumulative negative feedback mediated by a variety of end products of glutamine metabolism . Furthermore, the activity of the enzyme is controlled by reversible covalent modification . A certain tyrosine residue of each subunit of the enzyme is adenylated, whereby the inhibition is intensified by the negative feedback.
  • Class 2: This type, which consists of ten identical subunits, can be found in eukaryotes and certain bacteria. Several isoforms of class 2 glutamine synthetase are found in plants.
  • Class 3: GSIII has so far only been found in the bacteria Bacteroides fragilis and Butyrivibrio fibrisolvens .

Catalyzed reaction

Glutamate + ATP + NH 3 → glutamine + ADP + phosphate + H 2 O

Glutamine synthesis.

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  1. UniProt P15104