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Normal Function
The GSS gene provides instructions for making an enzyme called glutathione synthetase. Glutathione synthetase participates in a process called the gamma-glutamyl cycle. The gamma-glutamyl cycle is a sequence of chemical reactions that takes place in most of the body's cells. These reactions are necessary for the production of glutathione, a small molecule made of three protein building blocks (amino acids). Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules. Glutathione also helps process medications and cancer-causing compounds (carcinogens), and helps build DNA, proteins, and other important cellular components.
Health Conditions Related to Genetic Changes
Glutathione synthetase deficiency
More than 30 mutations in the GSS gene have been identified in people with glutathione synthetase deficiency. Characteristic features of this condition include the abnormal destruction of red blood cells (hemolytic anemia), the release of large amounts of a compound called 5-oxoproline in the urine (5-oxoprolinuria), and elevated acidity in the blood and tissues (metabolic acidosis). Severely affected individuals may also have neurological problems.
Most of the GSS mutations involved in glutathione synthetase deficiency change single amino acids in glutathione synthetase. Other mutations disrupt how genetic information from the GSS gene is pieced together to make a blueprint for producing the enzyme. The altered glutathione synthetase enzyme may be unstable, shorter than usual, or the wrong shape. All of these changes reduce the activity of the enzyme and disrupt the gamma-glutamyl cycle, preventing adequate production of glutathione. Low levels of glutathione affect other chemical reactions in the body, leading to the overproduction of 5-oxoproline. Accumulation of this compound in red blood cells and other tissues causes hemolytic anemia and metabolic acidosis, and its release leads to 5-oxoprolinuria.
More About This Health ConditionOther Names for This Gene
- gamma-L-Glutamyl-L-cysteine:glycine ligase (ADP-forming)
- glutathione synthase
- GSH synthetase
- GSHB_HUMAN
- GSHS
- MGC14098
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- De Jesus MC, Ingle BL, Barakat KA, Shrestha B, Slavens KD, Cundari TR, Anderson ME. The role of strong electrostatic interactions at the dimer interface of human glutathione synthetase. Protein J. 2014 Oct;33(5):403-9. doi: 10.1007/s10930-014-9573-y. Citation on PubMed or Free article on PubMed Central
- Dinescu A, Brown TR, Barelier S, Cundari TR, Anderson ME. The role of the glycine triad in human glutathione synthetase. Biochem Biophys Res Commun. 2010 Oct 1;400(4):511-6. doi: 10.1016/j.bbrc.2010.08.081. Epub 2010 Aug 26. Citation on PubMed or Free article on PubMed Central
- Dinescu A, Cundari TR, Bhansali VS, Luo JL, Anderson ME. Function of conserved residues of human glutathione synthetase: implications for the ATP-grasp enzymes. J Biol Chem. 2004 May 21;279(21):22412-21. doi: 10.1074/jbc.M401334200. Epub 2004 Feb 27. Citation on PubMed
- Janaky R, Ogita K, Pasqualotto BA, Bains JS, Oja SS, Yoneda Y, Shaw CA. Glutathione and signal transduction in the mammalian CNS. J Neurochem. 1999 Sep;73(3):889-902. doi: 10.1046/j.1471-4159.1999.0730889.x. Citation on PubMed
- Njalsson R, Carlsson K, Bhansali V, Luo JL, Nilsson L, Ladenstein R, Anderson M, Larsson A, Norgren S. Human hereditary glutathione synthetase deficiency: kinetic properties of mutant enzymes. Biochem J. 2004 Jul 15;381(Pt 2):489-94. doi: 10.1042/BJ20040114. Citation on PubMed or Free article on PubMed Central
- Njalsson R, Carlsson K, Olin B, Carlsson B, Whitbread L, Polekhina G, Parker MW, Norgren S, Mannervik B, Board PG, Larsson A. Kinetic properties of missense mutations in patients with glutathione synthetase deficiency. Biochem J. 2000 Jul 1;349(Pt 1):275-9. doi: 10.1042/0264-6021:3490275. Citation on PubMed or Free article on PubMed Central
- Ristoff E, Larsson A. Inborn errors in the metabolism of glutathione. Orphanet J Rare Dis. 2007 Mar 30;2:16. doi: 10.1186/1750-1172-2-16. Citation on PubMed or Free article on PubMed Central
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