34 by: Gbemisola Adeya

Student : GBEMISOLA ADEYA

ENZYME: GLUTAMINE SYNTHETASE

E.C. number: 6.3.1.2

Location: The enzyme is mainly present in human tissue, but increased expression levels are noted in; Astrocytes of the brain, Perivenous hepatocytes of the liver, and kidneys.

Function: GS catalyzes the ATP-driven reaction that combines glutamate and ammonia to form glutamine. Its role in humans depends on its tissue distribution: In the brain: GS is primarily located in astrocytes, where it protects neurons from excitotoxicity by managing toxic ammonia levels and converting neurotoxic glutamate into harmless glutamine. It is also involved in neurotransmitter recycling and signal termination. In the liver: GS plays a key role in detoxifying ammonia.

Interesting facts:
a. Glutamine synthetase is present in both prokaryotes and eukaryotes, with similar structure overall. Prokaryotic Glutamine Synthetase (GSI) has a dodecameric structure. Mammalian Glutamine Synthetase (GSII) is octameric.
b. Alterations in GS activity are linked to several neurodegenerative diseases, such as Alzheimer’s in the brain, and conditions like hepatitis in the liver.
c. Regulation: Glutamine synthetase is tightly controlled by feedback inhibition, where end products like glutamine, AMP, and carbamoyl phosphate inhibit the enzyme’s function to prevent overproduction of glutamine.
d. Isoforms: Humans have multiple isoforms of the enzyme, each serving specific functions depending on the tissue, especially in the brain and liver.

References
•Frieg, Benedikt, et al. “Molecular Mechanisms of Glutamine Synthetase Mutations That Lead to Clinically Relevant Pathologies.” PLoS Computational Biology, U.S. National Library of Medicine, 2 Feb. 2016, pmc.ncbi.nlm.nih.gov/articles/PMC4737493/#sec001.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4737493/#sec001
• Glutamine synthetase. (2020, January 9). Wikipedia. https://en.wikipedia.org/wiki/Glutamine_synthetase
• Krajewski, W. W., Collins, R., Holmberg-Schiavone, L., Jones, T. A., Karlberg, T., & Mowbray, S. L. (2008). Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. Journal of Molecular Biology, 375(1), 217–228. https://doi.org/10.1016/j.jmb.2007.10.029
• Llorca, Oscar, et al. “The Three-Dimensional Structure of an Eukaryotic Glutamine Synthetase: Functional Implications of Its Oligomeric Structure.” Journal of Structural Biology, vol. 156, no. 3, Dec. 2006, pp. 469–479, https://doi.org/10.1016/j.jsb.2006.06.003. Accessed 22 May 2021.
• Issoglio, Federico M, et al. “Exploring the Catalytic Mechanism of Human Glutamine Synthetase by Computer Simulations.” Biochemistry, vol. 55, no. 42, 13 Oct. 2016, pp. 5907–5916, https://doi.org/10.1021/acs.biochem.6b00822. Accessed 28th Sept. 2024.
• Zuo, Wu, et al. “Characterization and Improved Properties of Glutamine Synthetase from Providencia Vermicola by Site-Directed Mutagenesis.” Scientific Reports, vol. 8, no. 1, 23 Oct. 2018, p. 15640, www.nature.com/articles/s41598-018-34022-5, https://doi.org/10.1038/s41598-018-34022-5.
• Libretexts. “Glutamine Synthetase.” Chemistry LibreTexts, 1 May 2022, chem.libretexts.org/Courses/Saint_Marys_College_Notre_Dame_IN/CHE
M_342%3A_Bio-m inorganic_Chemistry/Readings/Metals_in_Biological_Systems_%28Saint_Mary%27s_College%29/Glutamine_Synthetase.