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MetaCyc Pathway: glutathione-mediated detoxification II
Inferred from experiment

Pathway diagram: glutathione-mediated detoxification II

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Detoxification

Some taxa known to possess this pathway include : Arabidopsis thaliana col

Expected Taxonomic Range: Viridiplantae

Glutathion plays an important role in cellular redox control and detoxification of heavy metals, electrophilic xenobiotics, and toxic side products of normal plant metabolism. The detoxification process starts with the formation of glutathione conjugates (GS-conjugates). This occurs in the cytosol. The subsequent degradation of GS-conjugates may occur in either cytosol or vacuole. In Arabidopsis, the degradation routes are different in the two subcellular locations. In the vacuole, the initial step of GS-conjugates degradation is catalyzed by γ-glutamyl transpeptidase, which removes the N-terminal glutamate residue [Grzam07]. This is also found to be the case in GS-conjugates degradation in human and animals. In the cytosol, however, the process starts with removal of the C-terminal glycine [Beck03]. So far this is only found in higher plants. Nonetheless, both routes lead to the common intermediate Cys-S-conjugates. Less is known about further degradation of Cys-S-conjugates. A major enzyme activity has been detected in an Arabidopsis cell culture that is involved in malonylation of Cys-S-conjugates to form N-malonyl-Cys-S-conjugates [BrazierHicks08]. In contrast, in human and animals, Cys-S-conjugates are acetylated to form N-acetyl-Cys-S-conjugates. In the Arabidopsis cell culture, a small portion of Cys-S-conjugates were converted to methyl thiolethers by the concerted action of a C-S lyase and a methyltransferase [BrazierHicks08].

Created 26-Jul-2011 by Zhang P, PMN


Beck03: Beck A, Lendzian K, Oven M, Christmann A, Grill E (2003). "Phytochelatin synthase catalyzes key step in turnover of glutathione conjugates." Phytochemistry 62(3);423-31. PMID: 12620355

BrazierHicks08: Brazier-Hicks M, Evans KM, Cunningham OD, Hodgson DR, Steel PG, Edwards R (2008). "Catabolism of glutathione conjugates in Arabidopsis thaliana. Role in metabolic reactivation of the herbicide safener fenclorim." J Biol Chem 283(30);21102-12. PMID: 18522943

Grzam07: Grzam A, Martin MN, Hell R, Meyer AJ (2007). "gamma-Glutamyl transpeptidase GGT4 initiates vacuolar degradation of glutathione S-conjugates in Arabidopsis." FEBS Lett 581(17);3131-8. PMID: 17561001

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Ahmad93: Ahmad H, Singhal SS, Saxena M, Awasthi YC (1993). "Characterization of two novel subunits of the alpha-class glutathione S-transferases of human liver." Biochim Biophys Acta 1161(2-3);333-6. PMID: 8431482

Attieh00: Attieh J, Sparace SA, Saini HS (2000). "Purification and properties of multiple isoforms of a novel thiol methyltransferase involved in the production of volatile sulfur compounds from Brassica oleracea." Arch Biochem Biophys 380(2);257-66. PMID: 10933880

Han04: Han Q, Li J (2004). "pH dependence, substrate specificity and inhibition of human kynurenine aminotransferase I." Eur J Biochem 271(23-24);4804-14. PMID: 15606768

Hiroi92: Hiroi Y, Endo Y, Natori Y (1992). "Purification and properties of an aminopeptidase from rat-liver cytosol." Arch Biochem Biophys 294(2);440-5. PMID: 1314542

Hirota85: Hirota T, Nishikawa Y, Takahagi H, Igarashi T, Kitagawa H (1985). "Simultaneous purification and properties of dehydropeptidase-I and aminopeptidase-M from rat kidney." Res Commun Chem Pathol Pharmacol 49(3);435-45. PMID: 2865778

Huangpu96: Huangpu J, Pak JH, Graham MC, Rickle SA, Graham JS (1996). "Purification and molecular analysis of an extracellular gamma-glutamyl hydrolase present in young tissues of the soybean plant." Biochem Biophys Res Commun 228(1);1-6. PMID: 8912628

Iizuka89: Iizuka M, Inoue Y, Murata K, Kimura A (1989). "Purification and some properties of glutathione S-transferase from Escherichia coli B." J Bacteriol 1989;171(11);6039-42. PMID: 2553668

Josch03: Josch C, Klotz LO, Sies H (2003). "Identification of cytosolic leucyl aminopeptidase (EC as the major cysteinylglycine-hydrolysing activity in rat liver." Biol Chem 384(2);213-8. PMID: 12675513

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Perry95: Perry S, Harries H, Scholfield C, Lock T, King L, Gibson G, Goldfarb P (1995). "Molecular cloning and expression of a cDNA for human kidney cysteine conjugate beta-lyase." FEBS Lett 360(3);277-80. PMID: 7883047

Rankin80: Rankin BB, McIntyre TM, Curthoys NP (1980). "Brush border membrane hydrolysis of S-benzyl-cysteine-p-nitroanilide, and activity of aminopeptidase M." Biochem Biophys Res Commun 96(3);991-6. PMID: 6108111

Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216

Taylor93: Taylor A (1993). "Aminopeptidases: structure and function." FASEB J 7(2);290-8. PMID: 8440407

Yao96: Yao R, Nimec Z, Ryan TJ, Galivan J (1996). "Identification, cloning, and sequencing of a cDNA coding for rat gamma-glutamyl hydrolase." J Biol Chem 271(15);8525-8. PMID: 8621474

Yao96a: Yao R, Schneider E, Ryan TJ, Galivan J (1996). "Human gamma-glutamyl hydrolase: cloning and characterization of the enzyme expressed in vitro." Proc Natl Acad Sci U S A 93(19);10134-8. PMID: 8816764

Yoshida02: Yoshida Y, Nakano Y, Amano A, Yoshimura M, Fukamachi H, Oho T, Koga T (2002). "lcd from Streptococcus anginosus encodes a C-S lyase with alpha,beta-elimination activity that degrades L-cysteine." Microbiology 148(Pt 12);3961-70. PMID: 12480900

Zhao12: Zhao N, Ferrer JL, Moon HS, Kapteyn J, Zhuang X, Hasebe M, Neal Stewart C, Gang DR, Chen F (2012). "A SABATH Methyltransferase from the moss Physcomitrella patens catalyzes S-methylation of thiols and has a role in detoxification." Phytochemistry 81;31-41. PMID: 22795762

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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