Cited by 1,266Sulfur Compounds in BiologyGlutathione Transferases and PolymorphismsRedox biology and oxidative stress

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Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions

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Lushchak, Volodymyr I.·2012·Journal of Amino Acids

DOI 10.1155/2012/736837PMC PMC3303626

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Abstract

Glutathione (GSH) is a tripeptide, which has many biological roles including protection against reactive oxygen and nitrogen species. The primary goal of this paper is to characterize the principal mechanisms of the protective role of GSH against reactive species and electrophiles. The ancillary goals are to provide up-to-date knowledge of GSH biosynthesis, hydrolysis, and utilization; intracellular compartmentalization and interorgan transfer; elimination of endogenously produced toxicants; involvement in metal homeostasis; glutathione-related enzymes and their regulation; glutathionylation of sulfhydryls. Individual sections are devoted to the relationships between GSH homeostasis and pathologies as well as to developed research tools and pharmacological approaches to manipulating GSH levels. Special attention is paid to compounds mainly of a natural origin (phytochemicals) which affect GSH-related processes. The paper provides starting points for development of novel tools and provides a hypothesis for investigation of the physiology and biochemistry of glutathione with a focus on human and animal health.

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“Consequently, the parallel upregulation of genes involved in GSH metabolism as a direct effect of TetraSOD® supplementation might help maintain adequate GSH levels in the liver, protecting cells from oxidative damage [69].”
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“cytosolic low molecular mass sulfhydryl compound that acts as a cellular reducing and protective reagent against ROS (Maher et al., 2005; Lushchak, 2012).”
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“GSH (Glutathione) has an exceptional influence on many cell functions, including cell cycle regulation, gene expression, immune responses, protein function and cell death activation [38].”
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“This is fine for healthy cells that possess base-line millimolar concentrations of GSH [18].”
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“Below a certain critical threshold, depletion of GSH impairs cellular protective mechanisms resulting in cytotoxicity (Lushchak, 2012; Lu, 2009).”
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Alpha-ketoglutarate reduces ethanol toxicity in Drosophila melanogaster by enhancing alcohol dehydrogenase activity and antioxidant capacity
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“Given that the ability of AKG to serve as a glutamate precursor for glutathione biosynthesis has been shown previously in human erythrocytes (Lushchak, 2012; Whillier, Garcia, Chapman, Kuchel, & Raftos, 2011), we propose that the elevated AKG available from the diet could be partially used to increase glutathione bios…”
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“In our previous study, we showed an activation of antioxidant enzymes, catalase and glutathione reductase, together with an enhanced level of low-molecular-mass thiols, which are represented mainly by glutathione [33], in AKG-grown yeast cells at exponential phase [10].”
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“Extracellular glutathione results from synthesis, consumption and extrusion by producing cells 31 of glutamate to cysteine is the first and rate-limiting step in the biosynthesis of this tripeptide.”
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Authors: Lushchak, V. I.
Affiliations: Vasyl Stefanyk Carpathian National University (UA)
Corresponding author: Lushchak, Volodymyr I.
ORCID: Lushchak, Volodymyr I.
Venue: Journal of Amino Acids
Publisher: Wiley
Published: 2012-02-28
Volume: 2012
Pages: 1-26
ISSN: 2090-0104 (ISSN-L)
2090-0112
DOI: 10.1155/2012/736837
PMC: PMC3303626
OpenAlex: W2043037824
Cited by: 1,266
References: 283
Citations by year: 2026: 70 · 2025: 117 · 2024: 119 · 2023: 126 · 2022: 125 · 2021: 131 · 2020: 110 · 2019: 79 · 2018: 76 · 2017: 93 · 2016: 64 · 2015: 64 · 2014: 52 · 2013: 29 · 2012: 7
FWCI: 20.84
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/3.0/ (unspecified)
Locations: Journal of Amino Acids (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Ministry of Education and Science of Ukraine (0106U002245)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: glutathione, glutathione homeostasis, reactive oxygen species, reactive nitrogen species, glutathione synthesis, glutathione metabolism, metal homeostasis, glutathionylation, sulfhydryl groups, phytochemicals, disease pathology

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Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions

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