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Leukotriene C₄

Names
Systematic IUPAC name (5S,6R,7E,9E,11Z,14Z)-6-({(2R)-2--3--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
PubChem CID	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/s1Key: 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/s1Key: GWNVDXQDILPJIG-NXOLIXFEBR
SMILES CCCCC/C=C\C/C=C\C=C\C=C\((CCCC(=O)O)O)SC(/C(=N/CC(=O)O)/O)/N=C(\CC(C(=O)O)N)/O
Properties
Chemical formula	C30H47N3O9S
Molar mass	625.78 g·mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). N verify (what is  ?) Infobox references

Leukotriene C₄ (LTC₄) is a leukotriene. LTC₄ has been extensively studied in the context of allergy and asthma. In cells of myeloid origin such as mast cells, its biosynthesis is orchestrated by translocation to the nuclear envelope along with co-localization of cytosolic phospholipase A2 (cPLA2), arachidonate 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTC₄ synthase (LTC₄S), which couples glutathione to an LTA₄ intermediate. The MRP1 transporter then secretes cytosolic LTC₄ and cell surface proteases further metabolize it by sequential cleavage of the γ-glutamyl and glycine residues off its glutathione segment, generating the more stable products LTD₄ and LTE₄. All three leukotrienes then bind at different affinities to two G-protein coupled receptors: CYSLTR1 and CYSLTR2, triggering pulmonary vasoconstriction and bronchoconstriction.

In cells of non-haematopoietic lineage, endoplasmic reticulum (ER) stress and chemotherapy induce LTC₄ biosynthesis by transcriptionally upregulating and activating the enzyme microsomal glutathione-S-transferase 2 (MGST2). ER stress and chemotherapy also trigger nuclear translocation of the two LTC₄ receptors. Acting in an intracrine manner, LTC₄ then elicits nuclear translocation of NADPH oxidase 4 (NOX4), ROS accumulation and oxidative DNA damage. Besides being a potent lipid mediator in asthma and inflammation, LTC₄ was reported to be involved in several other diseases, such as allergic airway diseases, dermatological diseases, cardiovascular diseases, liver injury, atherosclerosis and colon cancer.

References

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. PMC 4682057. 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. PMC 2709038. 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. PMC 298757. PMID 12552108.

• Eicosanoids