EC - γ-glutamyl hydrolase

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IntEnz Enzyme Nomenclature


Accepted name:
γ-glutamyl hydrolase
Other names:
γ-Glu-X carboxypeptidase
carboxypeptidase G
folate conjugase
folic acid conjugase
lysosomal γ-glutamyl carboxypeptidase
poly(γ-glutamic acid) endohydrolase
poly(glutamic acid) hydrolase II
polyglutamate hydrolase
pteroyl-poly-γ-glutamate hydrolase
pteroylpoly-γ-glutamyl hydrolase
Systematic name:



A lysosomal or secreted, thiol-dependent peptidase, most active at acidic pH. Commonly studied with folylpoly-γ-glutamate as substrate, with which the initial cleavage may release glutamate or poly-γ-glutamate of two or more residues, according to the species of origin of the enzyme. Final products are pteroyl-α-glutamate (folic acid) and free glutamate. Highly specific for the γ-glutamyl bond, but not for the C-terminal amino acid (leaving group). Action on γ-glutamyl bonds is independent of an N-terminal pteroyl moiety, but it is not known whether an N-terminal γ-Glu residue can be hydrolysed. Type example of peptidase family C26. Formerly EC

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , MEROPS , NIST 74 , UniPathway
Protein domains and families: PROSITE:PDOC51275
Structural data: CSA , EC2PDB
Gene Ontology: GO:0034722 , GO:0008464
CAS Registry Number: 9074-87-7
UniProtKB/Swiss-Prot: (10) [show] [UniProt]


  1. McGuire, J.J. and Coward, J.K.
    Pteroylpolyglutamates: biosynthesis, degradation and function.
    In: Blakley, R.L. and Benkovic, S.J. (Eds.) Folates and Pterins, John Wiley and Sons, New York, 1984, 135-191
  2. Wang, Y., Nimec, Z., Ryan, T.J., Dias, J.A. and Galivan, J.
    The properties of the secreted γ-glutamyl hydrolases from H35 hepatoma cells.
    Biochim. Biophys. Acta 1164: 227-235 (1993). [PMID: 8343522]
  3. Yao, R., Rhee, M.S. and Galivan, J.
    Effects of γ-glutamyl hydrolase on folyl and antifolylpolyglutamates in cultured H35 hepatoma cells.
    Mol. Pharmacol. 48: 505-511 (1995). [PMID: 7565632]
  4. Yao, R., Schneider, E., Ryan, T.J. and Galivan, J.
    Human γ-glutamyl hydrolase: Cloning and characterization of the enzyme expressed in vitro.
    Proc. Natl. Acad. Sci. USA 93: 10134-10138 (1996). [PMID: 8816764]
  5. Yao, R., Nimec, Z., Ryan, T.J. and Galivan, J.
    Identification, cloning, and sequencing of a cDNA coding for rat γ-glutamyl hydrolase.
    J. Biol. Chem. 271: 8525-8528 (1996). [PMID: 8621474]

[EC created 1972 as EC, transferred 1978 to EC, transferred 1992 to EC, modified 1997]