Leukotriene C4
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Names | |
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Systematic IUPAC name
(5S,6R,7E,9E,11Z,14Z)-6-({(2R)-2-[(4S)-4-Amino-4-carboxybutanamido]-3-[(carboxymethyl)amino]-3-oxopropyl}sulfanyl)-5-hydroxyicosa-7,9,11,14-tetraenoic acid | |
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3D model (JSmol)
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ChEBI | |
ChemSpider | |
ECHA InfoCard | 100.212.805 |
EC Number |
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KEGG | |
MeSH | Leukotriene+C4 |
PubChemCID
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UNII | |
CompTox Dashboard(EPA)
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Properties | |
C30H47N3O9S | |
Molar mass | 625.78g·mol−1 |
Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa).
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Leukotriene C4(LTC4) is aleukotriene.LTC4has been extensively studied in the context ofallergyandasthma.[1][2]In cells ofmyeloidorigin such asmast cells,its biosynthesis is orchestrated by translocation to thenuclear envelopealong with co-localization ofcytosolic phospholipase A2(cPLA2),arachidonate 5-lipoxygenase(5-LO),5-lipoxygenase-activating protein(FLAP) andLTC4synthase(LTC4S), which couplesglutathioneto anLTA4intermediate. TheMRP1 transporterthen secretes cytosolic LTC4and cell surface proteases further metabolize it by sequential cleavage of the γ-glutamylandglycineresidues off its glutathione segment, generating the more stable productsLTD4andLTE4.All three leukotrienes then bind at different affinities to twoG-protein coupled receptors:CYSLTR1andCYSLTR2,triggering pulmonaryvasoconstrictionandbronchoconstriction.[3]
In cells of non-haematopoieticlineage,endoplasmic reticulum(ER) stress andchemotherapyinduce LTC4biosynthesis by transcriptionally upregulating and activating the enzymemicrosomal glutathione-S-transferase 2(MGST2). ER stress and chemotherapy also trigger nuclear translocation of the two LTC4receptors. Acting in anintracrinemanner, LTC4then elicits nuclear translocation ofNADPH oxidase 4(NOX4), ROS accumulation and oxidative DNA damage.[4]Besides being a potent lipid mediator in asthma and inflammation, LTC4was reported to be involved in several other diseases, such as allergic airway diseases, dermatological diseases, cardiovascular diseases, liver injury, atherosclerosis and colon cancer.[5][6][7]
![](https://upload.wikimedia.org/wikipedia/commons/thumb/0/04/Eicosanoid_synthesis.png/320px-Eicosanoid_synthesis.png)
References
[edit]- ^Jakobsson, Per-Johan; Mancini, Joseph A.; Ford-Hutchinson, Anthony W. (1996-09-06)."Identification and Characterization of a Novel Human Microsomal Glutathione S-Transferase with Leukotriene C4 Synthase Activity and Significant Sequence Identity to 5-Lipoxygenase-activating Protein and Leukotriene C4 Synthase".Journal of Biological Chemistry.271(36): 22203–22210.doi:10.1074/jbc.271.36.22203.ISSN0021-9258.PMID8703034.
- ^Di Gennaro, Antonio; Haeggström, Jesper Z. (2012-01-01). "The Leukotrienes: Immune-Modulating Lipid Mediators of Disease". In Alt, Frederick W. (ed.).Chapter Two - The Leukotrienes: Immune-Modulating Lipid Mediators of Disease.Advances in Immunology. Vol. 116. Academic Press. pp. 51–92.doi:10.1016/b978-0-12-394300-2.00002-8.ISBN9780123943002.PMID23063073.
- ^Haeggström, Jesper Z.; Funk, Colin D. (2011-09-22). "Lipoxygenase and Leukotriene Pathways: Biochemistry, Biology, and Roles in Disease".Chemical Reviews.111(10): 5866–5898.doi:10.1021/cr200246d.PMID21936577.
- ^Dvash, Efrat; Har-Tal, Michal; Barak, Sara; Meir, Ofir; Rubinstein, Menachem (2015-12-11)."Leukotriene C4 is the major trigger of stress-induced oxidative DNA damage".Nature Communications.6:10112.Bibcode:2015NatCo...610112D.doi:10.1038/ncomms10112.PMC4682057.PMID26656251.
- ^Ma, Kui-Fen; Yang, Hong-Yu; Chen, Zhe; Qi, Luo-Yang; Zhu, Dan-Yan; Lou, Yi-Jia (2008-05-07)."Enhanced expressions and activations of leukotriene C4 synthesis enzymes in D-galactosamine/lipopolysaccharide-induced rat fulminant hepatic failure model".World Journal of Gastroenterology.14(17): 2748–2756.doi:10.3748/wjg.14.2748.ISSN1007-9327.PMC2709038.PMID18461660.
- ^Rigas, B. (1993). "Altered eicosanoid levels in human colon cancer".J Lab Clin Med.122(5): 518–23.PMID8228569.
- ^Spanbroek, Rainer; Grabner, Rolf; Lotzer, Katharina; Hildner, Markus; Urbach, Anja; Ruhling, Katharina; Moos, Michael P. W.; Kaiser, Brigitte; Cohnert, Tina U. (2003-02-04)."Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis".Proceedings of the National Academy of Sciences of the United States of America.100(3): 1238–1243.Bibcode:2003PNAS..100.1238S.doi:10.1073/pnas.242716099.ISSN0027-8424.PMC298757.PMID12552108.