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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
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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 [Yao96], 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) [Yao96a]. 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 [Yao96].

Molecular Weight of Polypeptide: 36 kD (experimental) [Yao96 ]

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 [Yao96]
Glycosylation-Site unspecified
The protein contains four potential Asn-containing glycosylation sites [Yao96]


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, 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

Yao96a: 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


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 Dec 20, 2014, biocyc12.