Glutathione synthetase
Glutathione synthetase | |||||||
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Chr. 20 q11.2 | |||||||
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Eukaryotic glutathione synthase | |||||||||
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glutathione synthase | |||||||||
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ExPASy NiceZyme view | | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Eukaryotic glutathione synthase, ATP binding domain | |||||||||
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Prokaryotic glutathione synthetase, N-terminal domain | |||||||||
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Prokaryotic glutathione synthetase, ATP-grasp domain | |||||||||
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Glutathione synthetase (GSS) (
In humans, defects in GSS are inherited in an
In
Structure
Human and yeast glutathione synthetases are
As of late 2007, 7
Mechanism
Glutathione synthase catalyzes the chemical reaction
- ATP + gamma-L-glutamyl-L-cysteine + glycine ADP + phosphate + glutathione
The 3
This enzyme belongs to the family of
The biosynthetic mechanisms for
Function
Glutathione synthetase is important for a variety of biological functions in multiple organisms. In
In humans, glutathione synthetase functions in a similar manner. Its product GSH participates in cellular pathways involved in homeostasis and cellular maintenance. For instance, glutathione peroxidases catalyze the oxidation of GSH to glutathione disulfide (GSSG) by reducing free radicals and reactive oxygen species such as hydrogen peroxide.[18] Glutathione S-transferase uses GSH to clean up various metabolites, xenobiotics, and electrophiles to mercapturates for excretion.[19] Because of its antioxidant role, GSS mostly produce GSH inside the cytoplasm of liver cells and imported to mitochondria where detoxification occurs.[20] GSH is also essential for the activation of the immune system to generate robust defense mechanisms against invading pathogens.[19] GSH is capable of preventing infection from the influenza virus.[21][22]
Clinical significance
Patients with mutations in the GSS gene develop glutathione synthetase (GSS) deficiency, an autosomal recessive disorder.[23] Patients develop a wide range of symptoms depending on the severity of the mutations. Mildly affected patients experience a compensated haemolytic anaemia because mutations affect stability of the enzyme. Moderately and severely affected individuals have enzymes with dysfunctional catalytic sites, rendering it unable to participate in detoxification reactions. Physiological symptoms include metabolic acidosis, neurological defects, and increased susceptibility to pathogenic infections.[4]
Treatment of individuals with
See also
References
- PMID 12467574.
- PMID 15981742.
- ^ PMID 12909715.
- ^ S2CID 59244.
- ^ O'Neill M. "Glutathione Synthetase Deficiency". Online Mendelian Inheritance in Man.
- ^ PMID 10369661.
- ^ ISBN 978-0-471-78624-5.
- PMID 21920581.
- PMID 20045436.
- PMID 9416615.
- ISBN 978-3-642-67132-6.
- PMID 8810901.
- ^ "Synthases and Ligases". IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN), and Nomenclature Commission of IUB (NC-IUB), Newsletter. 1984. Archived from the original on 2012-10-15. Retrieved 2016-03-02.
- PMID 17452339.
- PMID 20200426.
- PMID 11402187.
- ISBN 978-94-007-5786-8. Archived from the original(PDF) on 23 November 2015. Retrieved 2 March 2016.
- PMID 12167058.
- ^ PMID 12361782.
- ^ PMID 25024695.
- PMID 12818476.
- PMID 12654482.
- PMID 11445798.
- S2CID 205512465.
- PMID 8301428.
- PMID 17397529.
- Law MY, Halliwell B (1986). "Purification and properties of glutathione synthetase from (Spinacia oleracea) leaves". Plant Sci. 43 (3): 185–191. .
- Macnicol PK (1987). "Homoglutathione and glutathione synthetases of legume seedlings - partial-purification and substrate-specificity". Plant Sci. 53 (3): 229–235. .
External links
- Glutathione+Synthetase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)