Leukotriene C₄

Leukotriene C₄
Names
	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
Identifiers
CAS Number	72025-60-6;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:16978;
ChemSpider	4444133;
ECHA InfoCard	100.212.805
EC Number	200-659-6;
KEGG	C02166;
MeSH	Leukotriene+C4
PubChemCID	5280493;
UNII	2CU6TT9V48;
CompTox Dashboard(EPA)	DTXSID00903946;
	InChI InChI=1S/C30H47N3O9S/c1-2-3-4-5-6-7-8-9-10-11-12-13-16-25(24(34)15-14-17-27(36)37)43-21-23(29(40)32-20-28(38)39)33-26(35)19-18-22(31)30(41)42/h6-7,9-13,16,22-25,34H,2-5,8,14-15,17-21,31H2,1H3,(H,32,40)(H,33,35)(H,36,37)(H,38,39)(H,41,42)/b7-6-,10-9-,12-11+,16-13+/t22-,23-,24-,25+/m0/s1 Key: GWNVDXQDILPJIG-NXOLIXFESA-N; InChI=1/C30H47N3O9S/c1-2-3-4-5-6-7-8-9-10-11-12-13-16-25(24(34)15-14-17-27(36)37)43-21-23(29(40)32-20-28(38)39)33-26(35)19-18-22(31)30(41)42/h6-7,9-13,16,22-25,34H,2-5,8,14-15,17-21,31H2,1H3,(H,32,40)(H,33,35)(H,36,37)(H,38,39)(H,41,42)/b7-6-,10-9-,12-11+,16-13+/t22-,23-,24-,25+/m0/s1 Key: GWNVDXQDILPJIG-NXOLIXFEBR;
	SMILES CCCCC/C=C\C/C=C\C=C\C=C\[C@H]([C@H](CCCC(=O)O)O)SC[C@@H](/C(=N/CC(=O)O)/O)/N=C(\CC[C@@H](C(=O)O)N)/O;
Properties
Chemical formula	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). verify(what is?) Infobox references

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]

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.ISSN 0021-9258.PMID 8703034.
^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.ISBN 9780123943002.PMID 23063073.
^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.PMID 21936577.
^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.PMID 26656251.
^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.ISSN 1007-9327.PMC2709038.PMID 18461660.
^Rigas, B. (1993). "Altered eicosanoid levels in human colon cancer".J Lab Clin Med.122(5): 518–23.PMID 8228569.
^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.ISSN 0027-8424.PMC298757.PMID 12552108.

[1] 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.ISSN 0021-9258.PMID 8703034.

[2] 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.ISBN 9780123943002.PMID 23063073.

[3] 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.PMID 21936577.

[4] 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.PMID 26656251.

[5] 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.ISSN 1007-9327.PMC2709038.PMID 18461660.

[6] Rigas, B. (1993). "Altered eicosanoid levels in human colon cancer".J Lab Clin Med.122(5): 518–23.PMID 8228569.

[7] 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.ISSN 0027-8424.PMC298757.PMID 12552108.

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