Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
twitter

MetaCyc Enzyme: γ-glutamyl hydrolase

Gene: GGH Accession Number: G-3962 (MetaCyc)

Species: Homo sapiens

Summary:
The human gene encoding γ-glutamyl hydrolase was discovered based on its sequence similarity to the rat gene [Yao96a], with which it shares 67% identity. Like the rat gene it has a leader sequence of 24 amino acids, and is heavily glycosylated, with 4 potential Asn-containing glycosylation sites (the rat enzyme contains 7 such sites).

However, unlike the rat enzyme it is an endopeptidase. Acting in vitro on methotrexate pentaglutamate it cleaved the furthermost γ-glutamyl linkage, forming methotrexate tetraglutamate initially, followed by the triglutamte, diglutamate, and finally methotrexate (monoglutamate) [Yao96]. In addition, while the rat enzyme had no substrate preference between a diglutamate and pentaglutamate derivatives, the human enzyme clearly prefers the pentaglutamate form.

It should be mentioned that other researchers have purified another form of this enzyme from Jejunal brush borders [Chandler86]. That enzyme had a molecular weight of about 700 kDa, and upon denaturation, two polypeptides were observed, with molecular weights of 145 and 115 kDa. The relationship of these two proteins is not clear [Yao96a].

Molecular Weight of Polypeptide: 36 kD (experimental) [Yao96a ]

Relationship Links: Entrez-Nucleotide:PART-OF:NM_003878

Gene-Reaction Schematic: ?

Instance reaction of [a glutathione-toxin conjugate + H2O → a [Cys-Gly]-S-conjugate + L-glutamate] (3.4.19.9):
i1: 4-hydroxy-2-nonenal-glutathione conjugate + H2O → 4-hydroxy-2-nonenal-[Cys-Gly] conjugate + L-glutamate (3.4.19.9)

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers folic acid


Enzymatic reaction of: glutathione-toxin conjugate γ-glutamyl hydrolase

EC Number: 3.4.19.9

a glutathione-toxin conjugate + H2O <=> a [Cys-Gly]-S-conjugate + L-glutamate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: 4-hydroxy-2-nonenal detoxification , glutathione-mediated detoxification I


Enzymatic reaction of: folylpolyglutamate γ-glutamyl hydrolase

EC Number: 3.4.19.9

tetrahydropteroyl-[γ-Glu](n) + H2O <=> tetrahydropteroyl-[γ-Glu](n-1) + L-glutamate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: glutamate removal from folates


Sequence Features

Feature Class Location Comment
Signal-Sequence 1 -> 24
The first 24 amino acids are likely to encode a leader sequence [Yao96a]
Glycosylation-Site unspecified
The protein contains four potential Asn-containing glycosylation sites [Yao96a]


References

Chandler86: Chandler CJ, Wang TT, Halsted CH (1986). "Pteroylpolyglutamate hydrolase from human jejunal brush borders. Purification and characterization." J Biol Chem 261(2);928-33. PMID: 2867095

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


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Nov 22, 2014, biocyc14.