Any feedback?
Information on EC 5.2.1.2 - maleylacetoacetate isomerase
for references in articles please use BRENDA:EC5.2.1.2Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
5.2.1.2 maleylacetoacetate isomeraseIUBMB Comments
Also acts on maleylpyruvate.
Specify your search results
Word Map
- 5.2.1.2
- dichloroacetate
- fumarylacetoacetate
-
dca-induced
- succinylacetone
-
chlorofluoroacetic
- homogentisate
- tyrosinemia
- medicine
The enzyme appears in viruses and cellular organisms
Synonyms
gstz1, gstz1-1, maleylacetoacetate isomerase, glutathione transferase zeta, gstz1/maai, gstzeta/maai, mac-ti, atmaai, atgstz1, maleylacetone isomerase, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
GSTZ1-1
Isomerase, maleylacetoacetate
-
-
-
-
MAAI
MAc-tI
-
-
-
-
maleylacetoacetate isomerase
Maleylacetoacetic isomerase
-
-
-
-
Maleylacetone cis-trans-isomerase
-
-
-
-
Maleylacetone isomerase
-
-
-
-
additional information
glutathione transferase zeta 1, EC 2.5.1.18, bifunctional enzyme
MAAI
-
-
-
-
maleylacetoacetate isomerase
-
bifunctional enzyme EC 2.5.1.18, glutathione transferase Zeta, GSTZ1-1
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
4-Maleylacetoacetate = 4-fumarylacetoacetate
ordered sequence of binding: maleylacetone first followed by glutathione
-
4-Maleylacetoacetate = 4-fumarylacetoacetate
mechanism, preferred binding order is maleylacetone followed by glutathione
-
4-Maleylacetoacetate = 4-fumarylacetoacetate
tyrosine degradation leads to the formation of homogentisate, maleylacetoacetate isomerase, homogentisate dioxygenase and fumarylacetoacetate hydrolase are expressed in Arabidopsis thaliana to generate fumarate and acetoacetate
4-Maleylacetoacetate = 4-fumarylacetoacetate
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cis-trans-isomerization
cis-trans-isomerization
-
-
double bond
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
4-maleylacetoacetate cis-trans-isomerase
Also acts on maleylpyruvate.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
9023-75-0
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid + glutathione
2-(glutathion-S-yl)-3-(4-nitrophenyl)propanoic acid
Monomethyl 5-oxo-1(E),3(Z)-hexadien-1-ylphosphonate monoanion
Monomethyl 5-oxo-1(Z),3(E)-hexadien-1-ylphosphonate monoanion
-
cis-trans double isomerization
-
?
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid + glutathione
2-(glutathion-S-yl)-3-(4-nitrophenyl)propanoic acid
-
it is proposed that the charged side chain of Arg-175 forms a salt bridge with the carboxylate of the alpha-halo acid substrates
-
?
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid + glutathione
2-(glutathion-S-yl)-3-(4-nitrophenyl)propanoic acid
-
-
-
-
?
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
-
-
-
?
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
-
cis-trans double isomerization
-
?
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
-
r, reverse reaction is catalyzed in presence of GSH
-
?
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
-
cis-trans double isomerization
-
?
6-Oxo-2(E),4(Z)-heptanedienoic acid
6-Oxo-2(Z),4(E)-heptanedienoic acid
-
r, reverse reaction is catalyzed in presence of GSH
-
?
Maleylacetoacetate
?
human maleylacetoacetate isomerase deficiency presumably causes tyrosinemia that can be characterized by the absence of succinylacetone
-
-
?
Maleylacetoacetate
?
-
enzymatic isomerization of cis,cis-muconaldehydic acid to trans,trans-muconaldehydic acid followed by the oxidation is suggested to be the path to trans,trans-muconate
-
-
?
Maleylacetoacetate
?
-
one of the enzymes responsible for the oxidative metabolism of aromatic amino acids
-
-
?
Maleylpyruvate
Fumarylpyruvate
-
about 20fold higher activity than with maleylacetoacetate
-
?
additional information
?
-
-
enzyme deficiency would presumably cause tyrosinemia that would be characterized by the absence of succinylacetone
-
?
additional information
?
-
enzyme deficiency would presumably cause tyrosinemia that would be characterized by the absence of succinylacetone
-
?
additional information
?
-
key enzyme in the metabolic degradation of phenylalanine and tyrosine
-
?
additional information
?
-
-
key enzyme in the metabolic degradation of phenylalanine and tyrosine
-
?
additional information
?
-
-
the enzyme plays an important role in the metabolism of tyrosine
-
?
additional information
?
-
-
the bifunctional enzyme dehalogenates dichloroacetate to glyoxalate via its zeta-1 family glutathione transferase activity. Dichloroacetate is relevant to environmental science and allopathic medicine. The sensitivity to the inhibitor varies between enzyme haplotypes. Three nonsynonymous single-nucleotide polymorphisms of GSTz1/MAAI show different activity toward dichloroacetate and certain other xenobiotic haloacids
-
-
?
additional information
?
-
-
GSTzeta/MAAI is induced during the differentiation of 3T3-L1 fibroblasts into adipocytes. This process requires expression of C/EBPalpha as well as PPARgamma
-
-
?
additional information
?
-
-
the enzyme catalyzes the penultimate step in catabolic pathways for phenylalanine and tyrosine. BABL/c GSTZ1/MAAI-deficient mice show a number of significant abnormalities including altered organ sizes, an abnormal pattern of circulating leukocytes, and the consitutive induction of hepatic alpha, mu and pi class glutathione transferases
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL 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
Maleylacetoacetate
?
human maleylacetoacetate isomerase deficiency presumably causes tyrosinemia that can be characterized by the absence of succinylacetone
-
-
?
Maleylacetoacetate
?
-
enzymatic isomerization of cis,cis-muconaldehydic acid to trans,trans-muconaldehydic acid followed by the oxidation is suggested to be the path to trans,trans-muconate
-
-
?
Maleylacetoacetate
?
-
one of the enzymes responsible for the oxidative metabolism of aromatic amino acids
-
-
?
additional information
?
-
-
enzyme deficiency would presumably cause tyrosinemia that would be characterized by the absence of succinylacetone
-
?
additional information
?
-
enzyme deficiency would presumably cause tyrosinemia that would be characterized by the absence of succinylacetone
-
?
additional information
?
-
key enzyme in the metabolic degradation of phenylalanine and tyrosine
-
?
additional information
?
-
-
key enzyme in the metabolic degradation of phenylalanine and tyrosine
-
?
additional information
?
-
-
the enzyme plays an important role in the metabolism of tyrosine
-
?
additional information
?
-
-
GSTzeta/MAAI is induced during the differentiation of 3T3-L1 fibroblasts into adipocytes. This process requires expression of C/EBPalpha as well as PPARgamma
-
-
?
additional information
?
-
-
the enzyme catalyzes the penultimate step in catabolic pathways for phenylalanine and tyrosine. BABL/c GSTZ1/MAAI-deficient mice show a number of significant abnormalities including altered organ sizes, an abnormal pattern of circulating leukocytes, and the consitutive induction of hepatic alpha, mu and pi class glutathione transferases
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3Z)-1,3-butadiene-1,1,2,4-tetrol
competitive inhibitor identified by rational design, calculated to be no substrate and not inhibitory to CYP450 and nontoxic in AMES test
(Z)-3-[4-hydroxy-1-(hydroxymethyl)cyclohexyl]-2-propene-1,2-diol
competitive inhibitor identified by rational design, calculated to be no substrate and not inhibitory to CYP450 and nontoxic in AMES test
Dichloroacetate
-
the sensitivity to the inhibitor varies between enzyme haplotypes. Three nonsynonymous single-nucleotide polymorphisms of GSTz1/MAAI show different activity toward dichloroacetate and certain other xenobiotic haloacids
maleylacetone
-
inhibits isomerization of 6-oxo-2(E),4(Z)-heptanedienoic acid into 6-oxo-2(Z),4(E)-heptanedienoic acid, and the reverse reaction
NaBH4
-
inhibition in absence of substrate, increases activity in presence of substrate and GSH
S-Glutathioyl-N-hexylmaleamate
-
competitive towards GSH, uncompetitive towards maleylacetone
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Acidosis, Lactic
Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathways.
Acidosis, Lactic
Perturbation of maleylacetoacetic acid metabolism in rats with dichloroacetic Acid-induced glutathione transferase zeta deficiency.
Acidosis, Lactic
Prenatal and postnatal expression of glutathione transferase ? 1 in human liver and the roles of haplotype and subject age in determining activity with dichloroacetate.
Amyotrophic Lateral Sclerosis
Glutathione S-transferase Omega 2 DD genotype is associated with an increased risk of sporadic amyotrophic lateral sclerosis in Chinese men.
Breast Neoplasms
Investigation of glutathione S-transferase zeta and the development of sporadic breast cancer.
Breast Neoplasms
No evidence for glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 in breast cancer risk.
Carcinogenesis
GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
Carcinoma, Hepatocellular
GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
Carcinoma, Hepatocellular
GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate.
Carcinoma, Hepatocellular
GSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2/GPX4 axis.
Carcinoma, Hepatocellular
GSTZ1-1 downregulates Wnt/?-catenin signalling in hepatocellular carcinoma cells.
Hematologic Neoplasms
GSTZ1 genotypes correlate with dichloroacetate pharmacokinetics and chronic side effects in multiple myeloma patients in a pilot phase 2 clinical trial.
Liver Failure
Gene structure, chromosomal location, and expression pattern of maleylacetoacetate isomerase.
Lung Neoplasms
Pattern of antioxidant and DNA repair gene expression in normal airway epithelium associated with lung cancer diagnosis.
Macular Degeneration
Susceptibility to exudative age-related macular degeneration and three genetic polymorphisms of glutathione S-transferase Z1 (GSTZ1).
maleylacetoacetate isomerase deficiency
Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathways.
maleylacetoacetate isomerase deficiency
Dichloroacetic acid up-regulates hepatic glutathione synthesis via the induction of glutamate-cysteine ligase.
maleylacetoacetate isomerase deficiency
Exposure of Rats to Multiple Oral Doses of Dichloroacetate Results in Upregulation of Hepatic GSTs and NQO1.
maleylacetoacetate isomerase deficiency
GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
maleylacetoacetate isomerase deficiency
GSTZ1-1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone.
maleylacetoacetate isomerase deficiency
Hypersuccinylacetonaemia and normal liver function in maleylacetoacetate isomerase deficiency.
maleylacetoacetate isomerase deficiency
Oncometabolite modification of Keap1 links GSTZ1 deficiency with cancer.
maleylacetoacetate isomerase deficiency
Perturbation of maleylacetoacetic acid metabolism in rats with dichloroacetic Acid-induced glutathione transferase zeta deficiency.
maleylacetoacetate isomerase deficiency
Phenylalanine-induced leucopenia in genetic and dichloroacetic acid generated deficiency of glutathione transferase Zeta.
Multiple Myeloma
GSTZ1 genotypes correlate with dichloroacetate pharmacokinetics and chronic side effects in multiple myeloma patients in a pilot phase 2 clinical trial.
Neoplasms
Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate.
Neoplasms
GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
Neoplasms
GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate.
Neoplasms
GSTZ1-1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone.
Neoplasms
GSTZ1-1 downregulates Wnt/?-catenin signalling in hepatocellular carcinoma cells.
Neoplasms
p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance.
Neoplasms
Prenatal and postnatal expression of glutathione transferase ? 1 in human liver and the roles of haplotype and subject age in determining activity with dichloroacetate.
Neuroblastoma
p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance.
Ovarian Neoplasms
A panel of three oxidative stress-related genes predicts overall survival in ovarian cancer patients received platinum-based chemotherapy.
Pregnancy Complications
Effect modification of CPY2E1 and GSTZ1 genetic polymorphisms on associations between prenatal disinfection by-products exposure and birth outcomes.
Stomach Neoplasms
Glutathione S-transferase Z1 (GSTZ1) gene polymorphism in gastric cancer: a preliminary study in a Turkish population.
Tyrosinemias
Gene structure, chromosomal location, and expression pattern of maleylacetoacetate isomerase.
Urinary Bladder Neoplasms
A case-control study of polymorphisms in xenobiotic and arsenic metabolism genes and arsenic-related bladder cancer in New Hampshire.
Urinary Bladder Neoplasms
Genotoxicity of disinfection byproducts and disinfected waters: A review of recent literature.
Urinary Bladder Neoplasms
Polymorphisms in GSTT1, GSTZ1, and CYP2E1, Disinfection Byproducts, and Risk of Bladder Cancer in Spain.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.023
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme R175A
0.027
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme R175K
0.029
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1d-1d
0.044
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1c-1c
0.096
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1b-1b
0.128
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1a-1a
0.319
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme S15A
0.417
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme C16A
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.19
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme R175A
0.55
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1d-1d
0.59
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1c-1c
0.61
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme R175K
0.82
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1b-1b
1
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme S15A
1.3
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1a-1a
2.55
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme C16A
6.08
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1b-1b
6.08
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, enzyme hGSTZ1c-1c
6.08
(+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
-
pH 7.6, 25°C, mutant enzyme R175K
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
spectrophotometric assay with (+/-)-2-bromo-3-(4-nitrophenyl)propionic acid
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10.5 - 11
-
reaction with (+/-)-2-bromo-3-(4-nitrophenyl)propionic acid and glutathione
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional enzyme, catalyzes reactions of EC 5.2.1.2 and glutathione-conjugating activity, EC 2.5.1.18
SwissProt
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
GSTzeta/MAAI is induced during the differentiation of 3T3-L1 fibroblasts into adipocytes. This process requires expression of C/EBPalpha as well as PPARgamma
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
human polymorphisms in the glutathione transferase zeta 1/maleylacetoacetate isomerase gene influence the toxicokinetics of dichloroacetate, GSTz1/MAAI haplotype significantly affects the kinetics and biotransformation of dichloroacetate. GSTz1/MAAI variants associated with the slowest rates of dichlorocacetate metabolism induce structural changes in the enzyme homodimer, predicting protein instability or abnormal protein-protein interactions. Enzyme inhibition also results in the accumulation of the potentially hepatotoxic tyrosine intermediates maleylacetoacetate and maleylacetone and of delta-aminolevulinate
metabolism
metabolism
-
catalyses a significant step in the catabolism of phenylalanine and tyrosine
metabolism
-
the bifunctional enzyme glutathione transferase zeta/maleylacetoacetate isomerase is the penultimate enzyme in the phenylalanine/tyrosine catabolic pathway
Show AA Sequence and Transmembrane Helices (6201 entries)
Longer loading times are possible. Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Longer loading times are possible. Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM