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  Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:16978  Y
ChemSpider	4444133  N
ECHA InfoCard	100.212.805
EC Number	200-659-6
KEGG	C02166  Y
MeSH	Leukotriene+C4
PubChem CID	5280493
UNII	2CU6TT9V48  Y
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 N Key: GWNVDXQDILPJIG-NXOLIXFESA-N 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	625.78 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N  verify  (what is  YN ?) Infobox references

Leukotriene C₄ (LTC₄) is a leukotriene. LTC₄ has been extensively studied in the context of allergy and asthma. ^{[1] [2]} 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. ^[3]

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. ^[4] 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. ^{[5] [6] [7]}

Eicosanoid synthesis. (Leukotrienes at right.)

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   978-0-12-394300-2. 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.