GS

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Glutamine synthetase (GS) is an enzyme that catalyzes the condensation of glutamate and ammonia to form glutamine, which plays an important role in nitrogen metabolism:

Glutamic acid + ATP + NH₃ → glutamine + ADP + phosphate

Glutamine synthetase uses ammonia produced by nitrate reduction, amino acid degradation and photorespiration. The amide group of glutamate is the nitrogen source for the metabolites of the glutamine pathway. Other reactions may occur through GS. The competition between ammonium ions and water, their binding affinity and the concentration of ammonium ions will affect the synthesis of glutamine and the hydrolysis of glutamine. If ammonium ions attack the acyl phosphate intermediate, glutamine will be formed; if water attack the intermediate, glutamine will be reformed. Due to the electrostatic force between the cation and the negatively charged bag, ammonium ions bind to GS more firmly than water. Another possible reaction is to produce γ-glutaminyl hydroxamate after NH₂OH is combined with GS instead of NH4⁺.

Figure 1. Enzyme structure of GS.

Classifications

• Glutamine synthetase can be divided into three categories:

GSI: Distributed in prokaryotes.

GSII: mainly distributed in eukaryotes and bacteria, such as rhizobia and actinomycetes.

GSIII: Only found in a few bacteria, such as Bacteroides fragilis and Vibrio cellulolyticus.

• There are a variety of GS isoenzymes distributed in the seeds, leaves, roots, nodules, fruits and other organs of higher plants, which are divided into three types: GS1, GS2, and GSx:

GS1: Cytoplasmic GS or cytosolic GS, encoded by 3-5 nuclear genes; it is mainly involved in the transfer of stored nitrogen sources during seed germination and the transfer and reuse of nitrogen sources during leaf senescence.

GS2: plastid GS or chloroplast GS, encoded by a nuclear gene; mainly involved in photorespiration and the assimilation process of ammonia produced by nitric acid reduction.

GSx: usually less content.

Principle of action

This reaction consumes adenosine triphosphate and requires the participation of magnesium or manganese ions. Glutamine can further be used as a donor of ammonia and react with ketoglutarate to produce glutamate through the action of glutamate synthetase. This is a major way for the transformation of inorganic nitrogen into organic nitrogen in higher plants. Glutamine is an important form of nitrogen storage in plants. When the concentration of ammonium ions in plants is high, glutamine is synthesized in large quantities, which can prevent poisoning by accumulation of ammonium ions. Glutamine, an amino acid, is not only used by cells to synthesize proteins, but also to transport ammonia. Free ammonium ions are toxic to organisms and cannot be too much in the blood, but some biological processes will produce free ammonium ions; therefore, glutamine is used to transport these ammonium ions. When cells need to transport excess ammonium ions, they use ammonium ions and glutamic acid to synthesize glutamine and consume ATP. This reaction is catalyzed by glutamine synthetase. This reaction is divided into two steps. The enzyme first reacts ATP with glutamic acid to produce γ-glutamyl phosphate; then ammonium ions come up to replace the phosphate. In the study of higher plants, GS is often defined as an enzyme necessary for plant ammonia assimilation. Human glutamine synthetase is called hGS.

Functions

GS in the brain is involved in the metabolic regulation of glutamate, the detoxification of brain ammonia, the absorption of ammonia, the recycling of neurotransmitters and the termination of neurotransmitter signals. The brain mainly exists in astrocytes. Astrocytes protect neurons from excitotoxicity by ingesting excessive amounts of ammonia and glutamate; in a hyperammonemic environment (high ammonia content), astroglial swelling occurs. Different opinions have solved the problem of astroglial swelling. A study showed that a morphological change occurred, thereby increasing the expression of GS in the glutamatergic region or reducing other adaptive effects of high levels of glutamate and ammonia; another view is that astrocyte swelling is Caused by the accumulation of glutamine. In order to prevent cortical glutamate levels and cortical water content from increasing, a study has been conducted to prevent GS activity in rats by using MSO.