4.4.1.20: leukotriene-C4 synthase
This is an abbreviated version!
For detailed information about leukotriene-C4 synthase, go to the full flat file.
Word Map on EC 4.4.1.20
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4.4.1.20
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asthma
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lta4
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cysteinyl
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5-lipoxygenase
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arachidonic
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eosinophil
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asthmatic
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flap
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bronchial
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eicosanoids
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aspirin
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cysteinyl-leukotrienes
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cys-lts
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cysltr1
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aspirin-induced
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bronchoconstriction
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5-lipoxygenase-activating
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aspirin-intolerant
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alox5ap
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montelukast
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1-chloro-2,4-dinitrobenzene
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mapeg
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aspirin-exacerbated
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rbl-1
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medicine
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bronchoconstrictors
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a23187-stimulated
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molecular biology
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drug development
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analysis
- 4.4.1.20
- asthma
- lta4
-
cysteinyl
-
5-lipoxygenase
-
arachidonic
-
eosinophil
-
asthmatic
- flap
- bronchial
-
eicosanoids
- aspirin
- cysteinyl-leukotrienes
-
cys-lts
-
cysltr1
-
aspirin-induced
-
bronchoconstriction
-
5-lipoxygenase-activating
-
aspirin-intolerant
-
alox5ap
- montelukast
- 1-chloro-2,4-dinitrobenzene
-
mapeg
-
aspirin-exacerbated
- rbl-1
- medicine
-
bronchoconstrictors
-
a23187-stimulated
- molecular biology
- drug development
- analysis
Reaction
Synonyms
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate:glutathione leukotriene-transferase (epoxide-ring-opening), EC 2.5.1.37, leukotriene A4:glutathione S-leukotrienyltransferase, leukotriene C4 synthase, leukotriene C4 synthetase, LT C4 synthase, LTC4 synthase, LTC4 synthetase, LTC4S, LTCS, synthase, leukotriene C4
ECTree
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General Information
General Information on EC 4.4.1.20 - leukotriene-C4 synthase
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evolution
physiological function
additional information
the enzyme belongs to the superfamily of membrane-associated proteins in eicosanoid and glutathione metabolism, which consists of six integral membrane proteins
evolution
the enzyme belongs to the superfamily of membrane-associated proteins in eicosanoid and glutathione metabolism, which consists of six integral membrane proteins. Although structural differences near the active site and along the C-terminal alpha-helix V suggest that the mouse and human enzymes may function differently in vivo
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A-444C polymorphism on the LTC4S gene is associated with aspirin-induced urticaria. The C allele is more frequent in patients with the cutaneous pattern of aspirin-induced urticaria and in patients with low skin reactivity to histamine. There is no association between A-444C and asthma, atopy, or total IgE levels
physiological function
LTC4S interacts in vitro with both 5-lipoxygenase activating protein and 5-lipoxygenase, these interactions involve distinct parts of LTC4S. 5-lipoxygenase activating protein binds to the N-terminal part/first hydrophobic region of LTC4S, whereas 5-lipoxygenase binds to the second hydrophilic loop of LTC4S. Direct interaction of 5-lipoxygenase and LTC4S in ionophore-stimulated (but not unstimulated) cells
physiological function
perennial allergic rhinitis biopsies show 3fold more cells immunostaining for LTC4 synthase compared with seasonal allergic rhinitis biopsies but this is not significant compared with normal biopsies, probably because normal biopsies show relatively high variability for LTC4 synthase
physiological function
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leukotrienes are a family of drug-like molecules involved in the pathobiology of bronchial asthma and are responsible for smooth muscle contraction
physiological function
the enzyme catalyzes the conjugation reaction between the fatty acid leukotriene A4 and GSH to form the pro-inflammatory leukotriene C4, an important mediator of asthma
physiological function
the enzyme catalyzes the conjugation reaction between the fatty acid leukotriene A4 and GSH to form the pro-inflammatory leukotriene C4, an important mediator of asthma
physiological function
GST2 knock-down by specific siRNA significantly depresses LTC4 contents with 27.0 % decrease at 24 h. Reactive oxygen species levels are elevated by 40.1% in vitro. Increased expression of GST2 leads to 1.56fold increase in LTC4 synthase activity
physiological function
in coincubations of platelets and polymorphonuclear leukocytes, inhibition of LTC4S leads to shunting of LTA4 toward anti-inflammatory lipoxin A4, which is significantly enhanced by simultaneous inhibition of LTA4H
physiological function
transcellular LTC4 biosynthesis takes place between neutrophils or 5-lipoxygenase-expressing HEK293 cells that produce LTA4 from arachidonic acid and HEK293 cells expressing LTC4S that transform LTA4 to LTC4
enzyme residue Trp116 is not essential for catalysis but helps position the omega-end of leukotriene A4
additional information
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enzyme residue Trp116 is not essential for catalysis but helps position the omega-end of leukotriene A4