Glutamine Synthetase of the Human Brain: Purification and Characterization

Abstract

Glutamine synthetase (GS) isolated from human brain formed a single band on sodium dodecyl sulfate-polyacrylamide gel with a molecular weight of 44,000. The enzyme had a specific activity of 179.2 U/mg protein when assayed by measuring the rate of the formation of gamma-glutamylhydroxamate using hydroxylamine as a substrate. In the presence of manganese ions, the relative activity of human brain GS was much lower than that of the sheep brain enzyme. The suppression of activity by increasing the ADP concentration, however, was less marked in the human enzyme than that in the sheep enzyme. Antibodies were raised in rabbits against the purified enzyme. The double-immunodiffusion technique disclosed cross-reactivities among GSs isolated from human, sheep, and rat brains, but the enzymes were not immunologically identical. Immunohistochemically, GS was localized in the cytoplasm of astrocytes in the human and rat brains and in pericentral hepatocytes of the liver.

Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis

“…Despite its expression in many organs, the main clinical pathology in GS deficiency is related to the central nervous system, where GS is mainly expressed in both astrocytes and oligodendrocytes [65,66,67], but also in Müller cells of the retina [68], ependymal cells, and in nitrergic neurons [69]. GS plays a key role in (i) protecting the neurons from excitotoxicity by capturing ammonia and glutamate in the glial cells; and (ii) supplying glutamine for glutamate and GABA synthesis in the glutamine-glutamate-GABA cycle, regulating the excitatory and inhibitory synaptic transmission of neurons (Figure 3) [6,70,71].…”

13N-Ammonia PET/CT for detection of recurrent glioma

“…Glutamine synthetase is the key enzyme responsible for metabolic trapping of 13 N-ammonia in the brain. This enzyme is mainly localized in the astrocytic cytoplasm and footplates [21]. However, neoplasms containing the oligodendroglial component often include a mixed population of cells, most predominantly astrocytes [22].…”

Gene Expression Profiles Predict Emergence of Psychiatric Adverse Events in HIV/HCV-Coinfected Patients on Interferon-Based HCV Therapy

“…Glutamine synthetase (GS) is a ubiquitous enzyme that catalyzes the conversion of ammonia and glutamate to glutamine 20 . GS is expressed from the GLUL gene throughout the brain, and it plays a central role in the detoxification of ammonia and in the metabolic regulation of the neurotransmitter glutamate 21 .…”