Glutathione: Overview of Its Protective Roles, Measurement, and Biosynthesis

Overview

Journal Mol Aspects Med

Specialties Biochemistry
Molecular Biology

Date 2008 Sep 18

PMID 18796312

Citations 774

Authors

Henry Jay Forman

Hongqiao Zhang

Alessandra Rinna

Affiliations

Soon will be listed here.

Abstract

This review is the introduction to a special issue concerning, glutathione (GSH), the most abundant low molecular weight thiol compound synthesized in cells. GSH plays critical roles in protecting cells from oxidative damage and the toxicity of xenobiotic electrophiles, and maintaining redox homeostasis. Here, the functions and GSH and the sources of oxidants and electrophiles, the elimination of oxidants by reduction and electrophiles by conjugation with GSH are briefly described. Methods of assessing GSH status in the cells are also described. GSH synthesis and its regulation are addressed along with therapeutic approaches for manipulating GSH content that have been proposed. The purpose here is to provide a brief overview of some of the important aspects of glutathione metabolism as part of this special issue that will provide a more comprehensive review of the state of knowledge regarding this essential molecule.

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References

Gipp J, Chang C, Mulcahy R . Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase. Biochem Biophys Res Commun. 1992; 185(1):29-35. DOI: 10.1016/s0006-291x(05)80950-7. View

Ralat L, Manevich Y, Fisher A, Colman R . Direct evidence for the formation of a complex between 1-cysteine peroxiredoxin and glutathione S-transferase pi with activity changes in both enzymes. Biochemistry. 2006; 45(2):360-72. DOI: 10.1021/bi0520737. View

Griffith O, Meister A . Excretion of cysteine and gamma-glutamylcysteine moieties in human and experimental animal gamma-glutamyl transpeptidase deficiency. Proc Natl Acad Sci U S A. 1980; 77(6):3384-7. PMC: 349620. DOI: 10.1073/pnas.77.6.3384. View

Lu S . Regulation of glutathione synthesis. Mol Aspects Med. 2008; 30(1-2):42-59. PMC: 2704241. DOI: 10.1016/j.mam.2008.05.005. View

Gipp J, Bailey H, Mulcahy R . Cloning and sequencing of the cDNA for the light subunit of human liver gamma-glutamylcysteine synthetase and relative mRNA levels for heavy and light subunits in human normal tissues. Biochem Biophys Res Commun. 1995; 206(2):584-9. DOI: 10.1006/bbrc.1995.1083. View

Eckl P . Genotoxicity of HNE. Mol Aspects Med. 2003; 24(4-5):161-5. DOI: 10.1016/s0098-2997(03)00010-4. View

Iles K, Liu R . Mechanisms of glutamate cysteine ligase (GCL) induction by 4-hydroxynonenal. Free Radic Biol Med. 2005; 38(5):547-56. DOI: 10.1016/j.freeradbiomed.2004.11.012. View

Cantin A, North S, Hubbard R, Crystal R . Normal alveolar epithelial lining fluid contains high levels of glutathione. J Appl Physiol (1985). 1987; 63(1):152-7. DOI: 10.1152/jappl.1987.63.1.152. View

Rinna A, Forman H . SHP-1 inhibition by 4-hydroxynonenal activates Jun N-terminal kinase and glutamate cysteine ligase. Am J Respir Cell Mol Biol. 2008; 39(1):97-104. PMC: 2438451. DOI: 10.1165/rcmb.2007-0371OC. View

10.

Forman H . Use and abuse of exogenous H2O2 in studies of signal transduction. Free Radic Biol Med. 2007; 42(7):926-32. PMC: 1945171. DOI: 10.1016/j.freeradbiomed.2007.01.011. View

11.

Krzywanski D, Dickinson D, Iles K, Wigley A, Franklin C, Liu R . Variable regulation of glutamate cysteine ligase subunit proteins affects glutathione biosynthesis in response to oxidative stress. Arch Biochem Biophys. 2004; 423(1):116-25. DOI: 10.1016/j.abb.2003.11.004. View

12.

Pallardo F, Markovic J, Garcia J, Vina J . Role of nuclear glutathione as a key regulator of cell proliferation. Mol Aspects Med. 2009; 30(1-2):77-85. DOI: 10.1016/j.mam.2009.01.001. View

13.

Akerboom T, Sies H . Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol. 1981; 77:373-82. DOI: 10.1016/s0076-6879(81)77050-2. View

14.

Boyland E, Chasseaud L . The role of glutathione and glutathione S-transferases in mercapturic acid biosynthesis. Adv Enzymol Relat Areas Mol Biol. 1969; 32:173-219. DOI: 10.1002/9780470122778.ch5. View

15.

Richman P, Meister A . Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. J Biol Chem. 1975; 250(4):1422-6. View

16.

Dickinson D, Levonen A, Moellering D, Arnold E, Zhang H, Darley-Usmar V . Human glutamate cysteine ligase gene regulation through the electrophile response element. Free Radic Biol Med. 2004; 37(8):1152-9. DOI: 10.1016/j.freeradbiomed.2004.06.011. View

17.

Hirota T, Nishikawa Y, Tanaka M, Igarashi T, Kitagawa H . Characterization of dehydropeptidase I in the rat lung. Eur J Biochem. 1986; 160(3):521-5. DOI: 10.1111/j.1432-1033.1986.tb10070.x. View

18.

Roum J, Buhl R, McElvaney N, Borok Z, Crystal R . Systemic deficiency of glutathione in cystic fibrosis. J Appl Physiol (1985). 1993; 75(6):2419-24. DOI: 10.1152/jappl.1993.75.6.2419. View

19.

Yang H, Wang J, Huang Z, Ou X, Lu S . Cloning and characterization of the 5'-flanking region of the rat glutamate-cysteine ligase catalytic subunit. Biochem J. 2001; 357(Pt 2):447-55. PMC: 1221971. DOI: 10.1042/0264-6021:3570447. View

20.

Choi J, Liu R, Kundu R, Sangiorgi F, Wu W, Maxson R . Molecular mechanism of decreased glutathione content in human immunodeficiency virus type 1 Tat-transgenic mice. J Biol Chem. 2000; 275(5):3693-8. DOI: 10.1074/jbc.275.5.3693. View