3.4.19.9: folate gamma-glutamyl hydrolase
This is an abbreviated version!
For detailed information about folate gamma-glutamyl hydrolase, go to the full flat file.
Word Map on EC 3.4.19.9
-
3.4.19.9
-
polyglutamates
-
methotrexate
-
polyglutamylation
-
antifolate
-
casei
-
monoglutamates
-
pteroylpolyglutamate
-
sumo
-
monoglutamylated
-
5-methyltetrahydrofolate
-
deconjugation
-
trienzyme
-
pentaglutamate
-
rad6
-
diglutamate
-
punicic
-
medicine
-
analysis
- 3.4.19.9
- polyglutamates
- methotrexate
-
polyglutamylation
- antifolate
- casei
- monoglutamates
- pteroylpolyglutamate
- sumo
-
monoglutamylated
- 5-methyltetrahydrofolate
-
deconjugation
-
trienzyme
- pentaglutamate
- rad6
- diglutamate
-
punicic
- medicine
- analysis
Reaction
Synonyms
At1g78680, AtGGH1, AtGGH2, carboxypeptidase G, conjugase, EC 3.4.12.10, EC 3.4.22.12, FGPH, folate conjugase, folate hydrolase, folic acid conjugase, folylpolyglutamate hydrolase, gamma-GH, gamma-Glu-X carboxypeptidase, gamma-glutamyl hydrolase, gamma-polyglutamic acid hydrolase, gammaGH, GGH, GGH2, hydrolase, gamma-glutamyl, LeGGH1, LeGGH2, LeGGH3, low gamma-glutamyl hydrolase, lysosomal gamma-glutamyl carboxypeptidase, PghP, poly(gamma-glutamic acid) endohydrolase, poly(glutamic acid) hydrolase II, polyglutamate hydrolase, pteroyl-poly-gamma-glutamate hydrolase, pteroylpoly-gamma-glutamyl hydrolase, zgammaGH
ECTree
3.4.19.9 folate gamma-glutamyl hydrolaseAdvanced search results
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results (Substrates Products
Substrates Products on EC 3.4.19.9 - folate gamma-glutamyl hydrolase
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SUBSTRATE 
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(4,4-difluoro)glutamyl-gamma-glutamate + H2O
(4,4-difluoro)glutamate + glutamate
-
the fluorine substitution results in a significant decrease in rates of hydrolysis under steady-state conditions due primarily to a 15fold increase in Km compared to the unsubstituted substrate
-
-
?
(poly-gamma-glutamate)n + H2O
(poly-gamma-glutamate)n-1 + glutamate
-
-
-
-
?
(poly-gamma-L-glutamate)n + H2O
oligo-gamma-L-glutamate
-
-
-
-
?
2,4-diamino-10-methyl-pteroylglutamyl-gamma-glutamate + H2O
2,4-diamino-10-methyl-pteroate + glutamate + gamma-glutamylglutamate
4-aminobenzoyl-(4,4-difluoro)glutamyl-gamma-glutamate + H2O
4-aminobenzoyl-(4,4-difluoro)glutamate + glutamate
-
the fluorine substitution results in a significant decrease in rates of hydrolysis under steady-state conditions due primarily to a 15fold increase in Km compared to the unsubstituted substrate
-
-
?
4-aminobenzoyl-penta-gamma-glutamate + H2O
4-aminobenzoylglutamate + tetra-gamma-glutamate
-
-
subsequently degraded to glutamic acid
?
4-aminobenzoyltriglutamate + H2O
?
-
at 13% the rate of pteroyltriglutamate hydrolysis
-
-
?
4-hydroxy-2-nonenal-glutathione conjugate + H2O
4-hydroxy-2-nonenal-[Cys-Gly] conjugate + L-glutamate
-
-
-
-
?
5,10-methenyltetrahydrofolate glutamate + H2O
5,10-methenyltetrahydrofolate + L-glutamate
-
-
-
?
5,10-methenyltetrahydrofolate heptaglutamate + 7 H2O
5,10-methenyltetrahydrofolate + 7 L-glutamate
-
-
-
?
5,10-methenyltetrahydrofolate hexaglutamate + 6 H2O
5,10-methenyltetrahydrofolate + 6 L-glutamate
-
-
-
?
5-formyltetrahydrofolate glutamate + H2O
5-formyltetrahydrofolate + L-glutamate
-
-
-
?
5-formyltetrahydrofolate heptaglutamate + 7 H2O
5-formyltetrahydrofolate + 7 L-glutamate
-
-
-
?
5-formyltetrahydrofolate hexaglutamate + 6 H2O
5-formyltetrahydrofolate + 6 L-glutamate
-
-
-
?
5-L-glutamyl-4-nitroanilide + H2O
L-glutamic acid + 4-nitroaniline
-
-
-
-
?
5-methyltetrahydrofolate glutamate + H2O
5-methyltetrahydrofolate + L-glutamate
-
-
-
?
5-methyltetrahydrofolate heptaglutamate + 7 H2O
5-methyltetrahydrofolate + 7 L-glutamate
-
-
-
?
5-methyltetrahydrofolate hexaglutamate + 6 H2O
5-methyltetrahydrofolate + 6 L-glutamate
-
-
-
?
L-glutamic acid gamma-(4-nitroanilide) + H2O
L-glutamic acid + 4-nitroaniline
-
-
-
-
?
methotrexate hexaglutamate + H2O
methotrexate pentaglutamate + methotrexate tetraglutamate + methotrexate triglutamate + methotrexate diglutamate + methotrexate monoglutamate
-
-
-
?
methotrexate penta-gamma-glutamate + H2O
methotrexate-gamma-glutamate + tetra-gamma-glutamate
-
-
subsequently degraded to glutamic acid
?
methotrexate pentaglutamate + H2O
methotrexate glutamate + tetra-gamma-L-glutamate
-
-
-
?
methotrexate pentaglutamate + H2O
methotrexate tetraglutamate + methotrexate triglutamate + methotrexate diglutamate + methotrexate monoglutamate + L-glutamate
-
-
-
?
methotrexate triglutamate + H2O
methotrexate monoglutamate + methotrexate diglutamate + glutamate
-
-
-
-
?
N5-methyltetrahydropteroyltetraglutamate + H2O
?
-
cleaves the terminal gamma-glutamyl residues, finally releasing a monoglutamyl end-product
-
-
?
p-aminobenzoylpentaglutamate + H2O
?
pABAGlu5
-
-
?
pteroylglutamylhexaglutamate + H2O
short-chain pteroylglutamates
-
-
after 60 min incubation, pteroylglutamate is the major product after 120 min, with quantitative recovery of free glutamate, enzyme is an exopeptidase which progressively hydrolyzes glutamyl units from pteroylpolyglutamate, leaving pteroylmonoglutamate as the folate form available for intestinal transport
?
2,4-diamino-10-methyl-pteroylglutamyl-gamma-glutamate + H2O
2,4-diamino-10-methyl-pteroate + glutamate + gamma-glutamylglutamate
-
-
bile enzyme at a ratio of 5:95 and plasma enzyme at a ratio of 23:77
?
2,4-diamino-10-methyl-pteroylglutamyl-gamma-glutamate + H2O
2,4-diamino-10-methyl-pteroate + glutamate + gamma-glutamylglutamate
-
-
bile enzyme at a ratio of 5:95 and plasma enzyme at a ratio of 23:77
?
glutathione + H2O
?
-
enzyme hydrolyses the physiological antioxidant glutathione, suggesting an involvement of the enzyme in the cellular defense mechanism against oxidative stress
-
-
?
glutathione + H2O
?
-
enzyme hydrolyses the physiological antioxidant glutathione, suggesting an involvement of the enzyme in the cellular defense mechanism against oxidative stress
-
-
?
p-aminobenzoyl-penta-gamma-glutamate + H2O
?
AtGGH1 cleaves pentaglutamates mainly to di- and triglutamates
-
-
?
p-aminobenzoyl-penta-gamma-glutamate + H2O
?
AtGGH2 cleaves pentaglutamates mainly to monoglutamates
-
-
?
poly-Glu + H2O
?
-
enzyme is specific for poly(gamma-glutamic) acid, but not for other gamma-glutamyl peptides or amides
endo-type specificity, 38% of the original poly-Glu with an average MW of 500000 is converted to smaller peptides, and then depolymerized to a mixture of gamma-oligopeptides which consist of only L-glutamic acid, L-glutamic acid monomer is negligible in the reaction mixture, the remaining 62% of poly(gamma-glutamic acid) are resistant to the enzyme action
?
poly-Glu + H2O
?
-
enzyme is specific for poly(gamma-glutamic) acid, but not for other gamma-glutamyl peptides or amides
endo-type specificity, 38% of the original poly-Glu with an average MW of 500000 is converted to smaller peptides, and then depolymerized to a mixture of gamma-oligopeptides which consist of only L-glutamic acid, L-glutamic acid monomer is negligible in the reaction mixture, the remaining 62% of poly(gamma-glutamic acid) are resistant to the enzyme action
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
-
removal of the poly-gamma-glutamate chains
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
-
gamma-glutamyl hydrolase, not glutamate carboxypeptidase II, hydrolyzes dietary folate in rat small intestine
-
-
?
polyglutamyl-folate + H2O
monoglutamyl folate + glutamate
removal of the poly-gamma-glutamate chains
-
-
?
polyglutamylfolate + H2O
?
-
bond cleavage occurs with equal facility at internal points of the peptide chain
-
-
?
polyglutamylfolate + H2O
?
-
longer chain gamma-glutamyl peptides are preferentially attacked by the enzyme
-
-
?
polyglutamylfolate + H2O
?
-
peptide bond cleavage occurs only at gamma-glutamyl bonds and the presence of a COOH-terminal gamma bond is essential for enzyme action
-
-
?
polyglutamylfolate + H2O
?
-
the cleavage of diglutamyl peptides is extremely slow
-
-
?
polyglutamylfolate + H2O
?
-
the cleavage of gamma bonds is independent of the NH2-terminal pteroyl moiety
-
-
?
polyglutamylfolate + H2O
?
-
the ability of the gamma polyglutamate and the inability of the alpha polyglutamate to serve as substrate confirm the requirement for a terminal gamma peptide bond
-
-
?
polyglutamylfolate + H2O
?
-
sequential hydrolysis of glutamates with the dissociation of substrate from enzymic surface following cleavage of each glutamate seems likely
-
-
?
polyglutamylfolate + H2O
?
-
longer chain gamma-glutamyl peptides are preferentially attacked by the enzyme
-
-
?
polyglutamylfolate + H2O
?
-
specificity towards analogs of pteroylglutamyl-gamma-glutamyl-gamma-glutamic acid
-
-
?
polyglutamylfolate + H2O
?
-
analogs of the general structure pteroylglutamyl-gamma-glutamyl-gamma-R serve as substrates, low degree of specificity with regard to the nature of the-R group
-
-
?
polyglutamylfolate + H2O
?
-
enzyme from mouse kidney shows mixed endo- and exopeptidase activity, the enzyme from all other normal tissues and tumor cells is consistent with endopeptidase activity
-
-
?
polyglutamylfolate + H2O
?
-
endo/random hydrolysis of gamma-glutamyl peptide bonds of pteroylpolyglutamate substrates yielding folic acid as the terminal product
-
-
?
pteroyl-penta-gamma-glutamate + H2O
?
AtGGH1 cleaves pentaglutamates mainly to di- and triglutamates
-
-
?
pteroyl-penta-gamma-glutamate + H2O
?
AtGGH2 cleaves pentaglutamates mainly monoglutamates
-
-
?
pteroylheptaglutamate + H2O
?
-
-
pteroylmonoglutamate + hexaglutamyl peptide
?
pteroylpolyglutamate + H2O
?
-
the enzyme is responsible for the intracellular cleavage of poly-gamma-glutamates
-
-
?
pteroylpolyglutamate + H2O
?
-
the enzyme is suggested to be involved in the destruction of microorganisms in granulocytes during phagocytosis
-
-
?
pteroylpolyglutamate + H2O
?
-
central enzyme in folyl and antifolylpoly-gamma-glutamate metabolism
-
-
?
pteroylpolyglutamate + H2O
?
-
key enzyme in the maintenance of cellular folylpolyglutamate concentration
-
-
?
pteroylpolyglutamate + H2O
?
-
central enzyme in folyl and antifolyl poly-gamma-glutamate metabolism
-
-
?
pteroylpolyglutamate + H2O
?
-
folate conjugase in the brush-border may accomplish the initial digestion of the dietary pteroylpolyglutamates
-
-
?
pteroylpolyglutamate + H2O
?
-
the enzyme progressively hydrolyzes glutamyl units from pteroylpolyglutamate, leaving pteroylmonoglutamate as the folate form available for intestinal transport
-
-
?
pteroylpolyglutamate + H2O
?
-
possible contribution of biliary enzyme to intestinal absorption of folate polyglutamates
-
-
?
pteroylpolyglutamate + H2O
?
-
pancreatic enzyme may act in vivo in folate digestion and absorption to initiate the deconjugation of dietary pteroylpolyglutamate prior to the action of jejunal brush-border enzyme
-
-
?
pteroyltriglutamate + H2O
pteroylglutamate + glutamate
-
-
+ pteroyldiglutamate
?
additional information
?
-
isoform GGH2 alone is able to completely deconjugate folates using 50-100 microg/g of sample for 1 h at 37°C in all matrices tested. It removes the tails of folylpolyglutamates from tomato fruit, black bean and peanut seeds, and alfalfa sprouts extracts
-
-
?
additional information
?
-
-
the enzyme specifically cleaves D- and L-polyglutamic acid, preferred to entirely of poly-D-glutamic acid, a component of the capsule produced by several strains of Bacillus subtilis, the enzyme has minimal activity in degrading Bacillus anthracis and to remove the capsule from the surface of bacilli, the poly-gamma-D-glutamic acid capsule, no effect on RAW264.7 murine macrophage phagocytosis, and only minimal enhancement of human host neutrophil killing
-
-
?
additional information
?
-
-
the enzyme hydrolyzes synthetically hydrolyzed oligo-gamma-L-glutamates, but not oligo-gamma-D-glutamates, and degrades polyglutamic acid to a hydrolyzed product of about 20 kDa with a ratio of D- and L-glutamic acids of 70:30, thus the enzyme cleaves the bond between two L-glutamic acid residues, overview
-
-
?
additional information
?
-
hydrolysis of the gamma-glutamate bond, resulting in folate-mono-Glu
-
-
?
additional information
?
-
-
hydrolysis of the gamma-glutamate bond, resulting in folate-mono-Glu
-
-
?
additional information
?
-
hydrolysis of the gamma-glutamate bond, resulting in folate-mono-Glu
-
-
?
additional information
?
-
-
enzyme does not show any transpeptidase activity
-
-
?
additional information
?
-
-
enzyme does not show any transpeptidase activity
-
-
?
additional information
?
-
-
the maximal velocity decreases in the order methothrexate hexaglutamate, methotrexate tetraglutamate, methotrexate pentaglutamate, methotrexate triglutamate
-
-
?
additional information
?
-
-
soluble enzyme has a requirement for sulfhydryl groups in the active site
-
-
?
additional information
?
-
-
the intracellular enzyme shows the greatest affinity for the complete folic acid molecule with longer glutamate chains
-
-
?
additional information
?
-
-
the intracellular enzyme cleaves both terminal and internal gamma-glutamate linkages, in contrast the brush-border enzyme catalyzes the hydrolysis of only terminal gamma-glutamate linkages
-
-
?
additional information
?
-
-
progressively removes gamma-glutamyl residues at acidic pH from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate (folic acid) and free gamma-glutamic acid, highly specific for the gamma-glutamyl bond, but not for the C-terminal amino acid (leaving group), action on gamma-glutamyl bonds is independent of an N-terminal pteroyl moiety
-
-
?
additional information
?
-
-
GGH catalyzes degradation of the active polyglutamates of natural folates and the antifolate methotrexate
-
-
?
additional information
?
-
-
key enzyme in the metabolism of folic acid and the pharmacology of many antifolate drugs
-
-
?
additional information
?
-
the CpG island methylator phenotype in colorectal cancer is defined as concomitant and frequent hypermethylation of CpG islands within gene promoter regions, and is correlated with low expression levels of the enzyme in primary cancer cells, GGH is involved in the folate pathway and in the development and/or progression of this phenotype, CIMP+-related clinicopathological and molecular features, overview
-
-
?
additional information
?
-
-
the enzyme cleaves gamma-polyglutamate chains attached to folates and anti-folates after they enter mammalian cells, the enzyme plays an important role in folate homeostasis and confers resistance to anti-folates, especially methotrexate, the drugs are dependent on polyglutamylation for activity, overview
-
-
?
additional information
?
-
-
the enzyme cleaves gamma-polyglutamate chains attached to folates and anti-folates after they enter mammalian cells, the enzyme plays an important role in folate homeostasis and confers resistance to anti-folates, especially methotrexate
-
-
?
additional information
?
-
-
no hydrolysis of N-carbobenzoxyphenylalanyl-alanine
-
-
?
additional information
?
-
-
protein-associated poly-gamma-glutamates are poor substrates
-
-
?
additional information
?
-
-
no hydrolysis of 4-amino-benzoyl-gamma-glutamate
-
-
?
additional information
?
-
key enzyme in the metabolism of folic acid and the pharmacology of many antifolate drugs
-
-
?
additional information
?
-
-
the enzyme cleaves gamma-polyglutamate chains attached to folates and anti-folates after they enter mammalian cells, the enzyme plays an important role in folate homeostasis and confers resistance to anti-folates, especially methotrexate
-
-
?
additional information
?
-
-
either deacylation or rearrangement of the enzyme-product complex is rate-limiting in the isopeptide hydrolysis reaction
-
-
?
additional information
?
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase
-
-
?
additional information
?
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase
-
-
?
additional information
?
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase
-
-
?
additional information
?
-
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase
-
-
?
additional information
?
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than p-aminobenzoylpentaglutamate
-
-
?
additional information
?
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than p-aminobenzoylpentaglutamate
-
-
?
additional information
?
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than p-aminobenzoylpentaglutamate
-
-
?
additional information
?
-
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than p-aminobenzoylpentaglutamate
-
-
?
additional information
?
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than pABAGlu5
-
-
?
additional information
?
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than pABAGlu5
-
-
?
additional information
?
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than pABAGlu5
-
-
?
additional information
?
-
-
folates typically have gamma-linked polyglutamyl tails that make them better enzyme substrates and worse transport substrates than the unglutamylated forms. The tail can be shortened or removed by the vacuolar enzyme gamma-glutamyl hydrolase. Cleaves PteGlu5 more efficiently than pABAGlu5
-
-
?
