Gamma-Glutamyl Hydrolase (gGH)

GGH catalyzes the hydrolysis of folylpoly-gamma-glutamates and antifolylpoly-gamma-glutamates by the removal of gamma-linked polyglutamates and glutamate.The cDNA encodes a 318-amino acid protein with a deduced amino acid sequence 67% identical to that of the rat enzyme. The N-terminal 24 residues are likely a leader sequence that mediates translocation of GGH into the endoplasmic reticulum for secretion. GGH also contains 4 potential N-glycosylation sites. Western blot analysis detected GGH at an apparent molecular mass of about 35 kD.human GGH showed higher activity toward the pentaglutamate derivative of methotrexate and had little activity against the diglutamate derivative. More than 60% of the total GGH activity was secreted into the medium of the 5 tumor cell lines examined.