IUBMB Enzyme Nomenclature


Accepted name: glutathione γ-glutamate hydrolase

Reaction: (1) glutathione + H2O = L-cysteinylglycine + L-glutamate
(2) a glutathione-S-conjugate + H2O = an (L-cysteinylglycine)-S-conjugate + L-glutamate

Other name(s): glutathionase; γ-glutamyltranspeptidase (ambiguous); glutathione hydrolase; GGT (gene name); ECM38 (gene name)

Comments: This is a bifunctional protein that also has the activity of EC, γ-glutamyltransferase. The enzyme binds its substrate by forming an initial γ-glutamyl-enzyme intermediate, releasing the L-cysteinylglycine part of the molecule. The enzyme then reacts with either a water molecule or a different acceptor substrate (usually an L-amino acid or a dipeptide) to form L-glutamate or a product containing a new γ-glutamyl isopeptide bond, respectively. The enzyme acts on glutathione, glutathione-S-conjugates, and, at a lower level, on other substrates with an N-terminal L-γ-glutamyl residue. It plays a crucial part in the glutathione-mediated xenobiotic detoxification pathway. The enzyme consists of two chains that are created by the proteolytic cleavage of a single precursor polypeptide.

Links to other databases: BRENDA, EXPASY, ExplorEnz, KEGG, MetaCyc, PDB, CAS registry number:


1. Hanigan, M.H. and Ricketts, W.A. Extracellular glutathione is a source of cysteine for cells that express γ-glutamyl transpeptidase. Biochemistry 32 (1993) 6302-6306. [PMID: 8099811]

2. Carter, B.Z., Wiseman, A.L., Orkiszewski, R., Ballard, K.D., Ou, C.N. and Lieberman, M.W. Metabolism of leukotriene C4 in γ-glutamyl transpeptidase-deficient mice. J. Biol. Chem. 272 (1997) 12305-12310. [PMID: 9139674]

3. Suzuki, H. and Kumagai, H. Autocatalytic processing of γ-glutamyltranspeptidase. J. Biol. Chem. 277 (2002) 43536-43543. [PMID: 12207027]

4. Okada, T., Suzuki, H., Wada, K., Kumagai, H. and Fukuyama, K. Crystal structures of γ-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate. Proc. Natl. Acad. Sci. USA 103 (2006) 6471-6476. [PMID: 16618936]

5. Boanca, G., Sand, A., Okada, T., Suzuki, H., Kumagai, H., Fukuyama, K. and Barycki, J.J. Autoprocessing of Helicobacter pylori γ-glutamyltranspeptidase leads to the formation of a threonine-threonine catalytic dyad. J. Biol. Chem. 282 (2007) 534-541. [PMID: 17107958]

6. Okada, T., Suzuki, H., Wada, K., Kumagai, H. and Fukuyama, K. Crystal structure of the γ-glutamyltranspeptidase precursor protein from Escherichia coli. Structural changes upon autocatalytic processing and implications for the maturation mechanism. J. Biol. Chem. 282 (2007) 2433-2439. [PMID: 17135273]

7. Grzam, A., Martin, M.N., Hell, R. and Meyer, A.J. γ-Glutamyl transpeptidase GGT4 initiates vacuolar degradation of glutathione S-conjugates in Arabidopsis. FEBS Lett. 581 (2007) 3131-3138. [PMID: 17561001]

8. Wickham, S., West, M.B., Cook, P.F. and Hanigan, M.H. Gamma-glutamyl compounds: substrate specificity of γ-glutamyl transpeptidase enzymes. Anal. Biochem. 414 (2011) 208-214. [PMID: 21447318]

9. Keillor, J.W., Castonguay, R. and Lherbet, C. Gamma-glutamyl transpeptidase substrate specificity and catalytic mechanism. Methods Enzymol. 401 (2005) 449-467. [PMID: 16399402]

[EC created 2011, modified 2019]

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