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Information on EC 4.4.1.20 - leukotriene-C4 synthase and Organism(s) Rattus norvegicus and UniProt Accession Q925U2

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EC Tree
IUBMB Comments
The reaction proceeds in the direction of addition. Not identical with EC 2.5.1.18, glutathione transferase.
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This record set is specific for:
Rattus norvegicus
UNIPROT: Q925U2
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Word Map
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
Synonyms
ltc4s, ltc4 synthase, leukotriene c4 synthase, ltc4 synthetase, leukotriene-c4 synthase, leukotriene c4 synthetase, lt c4 synthase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
leukotriene C4 synthase
-
LTC4 synthase
-
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate:glutathione leukotriene-transferase (epoxide-ring-opening)
-
-
-
-
leukotriene A4:glutathione S-leukotrienyltransferase
-
-
-
-
leukotriene C4 synthase
leukotriene C4 synthetase
LTC4 synthase
LTC4 synthetase
-
-
-
-
synthase, leukotriene C4
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
alkenyl group transfer
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
leukotriene-C4 glutathione-lyase (leukotriene-A4-forming)
The reaction proceeds in the direction of addition. Not identical with EC 2.5.1.18, glutathione transferase.
CAS REGISTRY NUMBER
COMMENTARY hide
90698-32-1
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
leukotriene A4 + glutathione
leukotriene C4
show the reaction diagram
free acid, 4°C, pH 7.35
-
-
r
leukotriene A4 free acid + glutathione
leukotriene C4
show the reaction diagram
-
-
-
?
leukotriene A4 methyl ester + glutathione
leukotriene C4 methyl ester
show the reaction diagram
4°C, pH 7.35
-
-
r
leukotriene C4
leukotriene A4 + glutathione
show the reaction diagram
-
-
-
r
leukotriene A4 + glutathione
leukotriene C4
show the reaction diagram
leukotriene A4 + glutathione
leukotriene C4 + H2O
show the reaction diagram
leukotriene A4 free acid + glutathione
leukotriene C4
show the reaction diagram
-
pH 7.4, 37°C
-
-
r
leukotriene A4 methyl ester + glutathione
leukotriene C4 methyl ester + H2O
show the reaction diagram
-
-
-
-
?
leukotriene A4 methylester + glutathione
leukotriene C4 methylester
show the reaction diagram
-
pH 7.4, 37°C
-
-
r
leukotriene C4
leukotriene A4 + glutathione
show the reaction diagram
-
-
-
-
r
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
leukotriene C4
leukotriene A4 + glutathione
show the reaction diagram
-
-
-
r
leukotriene C4
leukotriene A4 + glutathione
show the reaction diagram
-
-
-
-
r
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cysteinyl-leukotriene
-
bovine serum albumin
-
5 mg, 45% inhibition
-
estrone-3-sulfate
-
IC50: 1.9 mM
hexylglutathione
p-aminohippuric acid
-
IC50: 0.26 mM
probenecid
-
IC50: 17 mM
sodium nitroprusside
-
in hepatic ischemia-reperfusion injured rats
Sulfobromophthalein
-
IC50: 0.06 mM
additional information
-
cell treatment with ERK 1/2 specific inhibitor 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126) blocks LTC4S expression, pyrrolidine dithiocarbamate inhibits reactive oxygen species generation and NF-?B activation, which in turn blocks LTC4S expression
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
17-beta-estradiol-3-sulfate
-
stimulates
17-beta-estradiol-3-sulfate-17 glucuronide
-
stimulates
actinomycin D
-
in addition to retinoic acid
daunorubicin
-
-
estriol-3-sulfate
-
stimulates
lipopolysaccharide
-
from Escherichia coli serotype O26:B26, increases mRNA expression in heart, brain, liver and adrenal gland
mitomycin C
-
-
retinoic acid
-
-
additional information
-
expression and activity of LTC4S is upregulated after treatment with D-galactosamine/lipopolysaccharide in a fulminant hepatic failure model
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0188
leukotriene A4 free acid
4°C, pH 7.35
0.0198
leukotriene A4 methyl ester
4°C, pH 7.35
0.056 - 0.21
leukotriene A4
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.9
estrone-3-sulfate
Rattus norvegicus
-
IC50: 1.9 mM
0.26
p-aminohippuric acid
Rattus norvegicus
-
IC50: 0.26 mM
17
probenecid
Rattus norvegicus
-
IC50: 17 mM
0.06
Sulfobromophthalein
Rattus norvegicus
-
IC50: 0.06 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0562
with leukotriene A4 free acid as substrate
0.0813
with leukotriene A4 methyl ester as substrate
0.000399
-
differentiated cells
0.29
-
crude enzyme from homogenate, at 25°C
28
-
recombinant enzyme, after 97fold purification, at 25°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.8
-
lung enzyme, reaction with leukotriene A4 methyl ester
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9.69
calculated from amino acid sequence
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
throughout the gray matter
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
LTC4S_RAT
150
3
16850
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
16800
calculated from amino acid sequence
18000
-
x * 18000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 18000, SDS-PAGE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop vapour diffusion method using the MbClass and MbClass II suites
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40
-
5 min, 90% loss of activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-Sepharose column chromatography, S-hexylglutathione agarose chromatography, and Superdex 200 gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Spodoptera frugiperda
expressed as an N-terminal hexa-histidine-tagged fusion protein in Pichia pastoris KM71H cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
is not suppressed by pretreatment with the p38 inhibitor
LTC4s increases following spared nerve injury, significant increase 3 days after nerve injury and continues at least for 14 days. LTC4s mRNA is expressed constitutively throughout the grey matter and increases after nerve injury in dorsal horn. This increase in LTC4s mRNA mainly occurrs in cells with small nuclei
hepatic mRNA expression of LTC4S is decreased in presence of NO donor O2-vinyl-1-(pyrrolidin-1-yl)-diazen-1-ium-1,2-diolate, i.e. V-PYRRO/NO. Downregulation may occur via inhibiting NF-kappaB activation independent of IkappaBalpha during hepatic ischemia/reperfusion injury
G3V6E6
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
sodium nitroprusside inhibits leukotriene C4 synthase activity and dwonregulates the protein expression of the enzyme
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Nicholson, D.W.; Ali, A.; Klemba, M.W.; Munday, N.A.; Zamboni, R.J.; Ford-Hutchinson, A.W.
Human leukotriene C4 synthase expression in dimethyl sulfoxide-differentiated U937 cells
J. Biol. Chem.
267
17849-17857
1992
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Izumi, T.; Honda, Z.; Ohishi, N.; Kitamura, S.; Tsuchida, S.; Sato, K.; Shimizu, T.; Seyama, Y.
Solubilization and partial purification of leukotriene C4 synthase from guinea-pig lung: a microsomal enzyme with high specificity towards 5,6-epoxide leukotriene A4
Biochim. Biophys. Acta
959
305-315
1988
Cavia porcellus, Rattus norvegicus
Manually annotated by BRENDA team
Lam, B.K.; Frank Austen, K.
Leukotriene C4 synthase: a pivotal enzyme in cellular biosynthesis of the cysteinyl leukotrienes
Prostaglandins Other Lipid Mediat.
68-69
511-520
2002
Cavia porcellus, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Yoshimoto, T.; Soberman, R.J.; Lewis, R.A.; Austen, K.F.
Isolation and characterization of leukotriene C4 synthetase of rat basophilic leukemia cells
Proc. Natl. Acad. Sci. USA
82
8399-8403
1985
Rattus norvegicus
Manually annotated by BRENDA team
Tornhamre, S.; Sjolinder, M.; Lindberg, A.; Ericsson, I.; Nasman-Glaser, B.; Griffiths, W.J.; Lindgren, J.A.
Demonstration of leukotriene-C4 synthase in platelets and species distribution of the enzyme activity
Eur. J. Biochem.
251
227-235
1998
Bos taurus, Equus caballus, Homo sapiens, no activity in Sus scrofa, Oryctolagus cuniculus, Ovis aries, Rattus norvegicus
Manually annotated by BRENDA team
Wu, C.
Conversion of leukotrienes A4 to C4 in cell-free systems
Biochem. Biophys. Res. Commun.
134
85-92
1986
Cavia porcellus, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Soberman, R.J.; Yoshimoto, T.
Leukotriene C4 synthase from rat basophilic leukemia cell microsomes
Methods Enzymol.
163
353-357
1988
Rattus norvegicus
Manually annotated by BRENDA team
Bach, M.K.; Brashler, J.R.; Morton, D.R.
Solubilization and characterization of the leukotriene C4 synthetase of rat basophil leukemia cells: a novel, particulate glutathione S-transferase
Arch. Biochem. Biophys.
230
455-465
1984
Rattus norvegicus
Manually annotated by BRENDA team
Petric, R.; Nicholson, D.W.; Ford-Hutchinson, A.W.
Renal leukotriene C4 synthase: characterization, partial purification and alterations in experimental glomerulonephritis
Biochim. Biophys. Acta
1254
207-215
1995
Rattus norvegicus
Manually annotated by BRENDA team
Schroder, O.; Sjostrom, M.; Qiu, H.; Stein, J.; Jakobsson, P.J.; Haeggstrom, J.Z.
Molecular and catalytic properties of three rat leukotriene C4 synthase homologs
Biochem. Biophys. Res. Commun.
312
271-276
2003
Rattus norvegicus (Q925U2)
Manually annotated by BRENDA team
Schroder, O.; Sjostrom, M.; Qiu, H.; Jakobsson, P.J.; Haeggstrom, J.Z.
Microsomal glutathione S-transferases: selective up-regulation of leukotriene C4 synthase during lipopolysaccharide-induced pyresis
Cell. Mol. Life Sci.
62
87-94
2005
Rattus norvegicus
Manually annotated by BRENDA team
Abe, M.; Shibata, K.; Urata, H.; Sakata, N.; Katsuragi, T.
Induction of leukotriene C4 synthase after the differentiation of rat basophilic leukemia cells with retinoic acid and a low dose of actinomycin D and its suppression with methylprednisolone
J. Cell. Physiol.
196
154-164
2003
Rattus norvegicus
Manually annotated by BRENDA team
Yang, S.L.; Lou, Y.J.
Sodium nitroprusside decreased leukotriene C4 generation by inhibiting leukotriene C4 synthase expression and activity in hepatic ischemia-reperfusion injured rats
Biochem. Pharmacol.
73
724-735
2007
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Manually annotated by BRENDA team
Ma, K.; Zhang, Y.; Zhu, D.; Lou, Y.
Protective effects of asiatic acid against D-galactosamine/lipopolysaccharide-induced hepatotoxicity in hepatocytes and kupffer cells co-cultured system via redox-regulated leukotriene C4 synthase expression pathway
Eur. J. Pharmacol.
603
98-107
2009
Rattus norvegicus
Manually annotated by BRENDA team
Wetterholm, A.; Martinez Molina, D.; Nordlund, P.; Eshaghi, S.; Haeggstroem, J.Z.
High-level expression, purification, and crystallization of recombinant rat leukotriene C4 synthase from the yeast Pichia pastoris
Protein Expr. Purif.
60
1-6
2008
Rattus norvegicus
Manually annotated by BRENDA team
Ma, K.F.; Yang, H.Y.; Chen, Z.; Qi, L.Y.; Zhu, D.Y.; Lou, Y.J.
Enhanced expressions and activations of leukotriene C4 synthesis enzymes in D-galactosamine/lipopolysaccharide-induced rat fulminant hepatic failure model
World J. Gastroenterol.
14
2748-2756
2008
Rattus norvegicus
Manually annotated by BRENDA team
Okubo, M.; Yamanaka, H.; Kobayashi, K.; Noguchi, K.
Leukotriene synthases and the receptors induced by peripheral nerve injury in the spinal cord contribute to the generation of neuropathic pain
Glia
58
599-610
2010
Rattus norvegicus (Q925U2)
Manually annotated by BRENDA team
Hong, F.F.; Wang, Y.F.; Liu, H.; Yang, M.W.; Yang, S.L.
V-PYRRO/NO downregulates mRNA expression levels of leukotriene C4 synthase during hepatic ischemia reperfusion injury in rats via inhibition of the nuclear factor-kappaB activation pathway
Biomed. Rep.
4
112-116
2016
Rattus norvegicus (G3V6E6)
Manually annotated by BRENDA team