Leukotriene A4

Leukotriene A4 (LTA₄) is a leukotriene, and is the precursor for the productions of LTB₄ (leukotriene B4) and LTC₄ (leukotriene C4).

Leukotriene A4

Names
IUPAC name 4-{(2S,3S)-3-[(1E,3E,5Z,8Z)-1,3,5,8-Tetradecatetraen-1-yl]-2-oxiranyl}butanoic acid
Systematic IUPAC name 4-{(2S,3S)-3-[(1E,3E,5Z,8Z)-1,3,5,8-Tetradecatetraen-1-yl]-2-oxiranyl}butanoic acid
Identifiers
CAS Number	72059-45-1
3D model (JSmol)	Interactive image
ChEBI	CHEBI:15651
ChemSpider	4444074
IUPHAR/BPS	5214
KEGG	C00909
MeSH	D017572
PubChem CID	5280383
UNII	7Y7MPZ6563
CompTox Dashboard (EPA)	DTXSID40903945
InChI InChI=1S/C20H30O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-15-18-19(23-18)16-14-17-20(21)22/h6-7,9-13,15,18-19H,2-5,8,14,16-17H2,1H3,(H,21,22)/b7-6-,10-9-,12-11+,15-13+/t18-,19-/m0/s1 Key: UFPQIRYSPUYQHK-WAQVJNLQSA-N InChI=1/C20H30O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-15-18-19(23-18)16-14-17-20(21)22/h6-7,9-13,15,18-19H,2-5,8,14,16-17H2,1H3,(H,21,22)/b7-6-,10-9-,12-11+,15-13+/t18-,19-/m0/s1 Key: UFPQIRYSPUYQHK-WAQVJNLQBZ
SMILES CCCCC/C=C\C/C=C\C=C\C=C\[C@H]1[C@@H](O1)CCCC(=O)O
Properties
Chemical formula	C20H30O3
Molar mass	318.450
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Biosynthesis of Leukotriene A₄

Following the biosynthesis of eicosanoid, triggered as a result of infection or inflammation, the resulting arachidonic acid substrate is released from the cell membrane phospholipid will enter the lipooxygenase pathway to produce Leukotriene A4.[1][2] In this pathway, arachidonic acid is converted into 5-hydroperoxyeicosatetraenoic acid (5-HPETE) as a result of a catalytic complex consisting of the enzyme 5-lipoxygenase (5-LO) and FLAP (5-Lipoxygenase-activating protein) in the presence of ATP and Calcium ions.[3][4][5] The resulting 5-HPETE yields the unstable allylic epoxide substrate LTA₄[6] which is quickly hydrolyzed by the LTA₄H (Leukotriene A4 hydrolase) enzyme to produce LTB₄, or synthesized by LTC₄S (Leukotriene C4 synthase) with the addition of glutathione to produce LTC₄ which can be further metabolized to produce LTD4 (Leukotriene D4) and LTE4 (Leukotriene E4)_.[7][8] The lipooxygenase pathway is one of several possible pathways including the cyclooxygenase pathway (also PGH synthase pathway), isoprostane pathway, and cytochrome P450 epoxygenases pathway following the arachidonic acid metabolism,[9] but is the only pathway in which the subsequent steps will lead to the production of leukotrienes.

Eicosanoid synthesis' subsequent release of arachidonic acid will enter a pathway dependent on what molecule the body requires of the arachidonic acid to be converted into. (Right) The arachidonic acid will undergo the lipooxygenase pathway to produce leukotriene A₄ and subsequent leukotrienes in the case of inflammation.

References

1. Abu, J. I.; Konje, J. C. (March 2000). "Leukotrienes in gynaecology: the hypothetical value of anti-leukotriene therapy in dysmenorrhoea and endometriosis". Human Reproduction Update. 6 (2): 200–205. doi:10.1093/humupd/6.2.200. ISSN 1355-4786. PMID 10782578.
2. Marx, J. L. (1982-03-12). "The leukotrienes in allergy and inflammation". Science. 215 (4538): 1380–1383. Bibcode:1982Sci...215.1380M. doi:10.1126/science.6278589. ISSN 0036-8075. PMID 6278589.
3. Marx, J. L. (1982-03-12). "The leukotrienes in allergy and inflammation". Science. 215 (4538): 1380–1383. Bibcode:1982Sci...215.1380M. doi:10.1126/science.6278589. ISSN 0036-8075. PMID 6278589.
4. Nicolls, Mark R.; Voelkel, Norbert F.; Peters-Golden, Marc; Rajadas, Jayakumar; Fridlib, Marina; Inayathullah, Mohammed; Zamanian, Roham T.; Rabinovitch, Marlene; Farkas, Laszlo (2013-08-28). "Blocking Macrophage Leukotriene B4 Prevents Endothelial Injury and Reverses Pulmonary Hypertension". Science Translational Medicine. 5 (200): 200ra117. doi:10.1126/scitranslmed.3006674. ISSN 1946-6234. PMC 4016764. PMID 23986401.
5. Abu, J. I.; Konje, J. C. (March 2000). "Leukotrienes in gynaecology: the hypothetical value of anti-leukotriene therapy in dysmenorrhoea and endometriosis". Human Reproduction Update. 6 (2): 200–205. doi:10.1093/humupd/6.2.200. ISSN 1355-4786. PMID 10782578.
6. Serhan, C. N.; Rouzer, C. A.; Lindgren, J. A.; Dahlen, S. E.; Samuelsson, B. (1987-09-04). "Leukotrienes and lipoxins: structures, biosynthesis, and biological effects". Science. 237 (4819): 1171–1176. Bibcode:1987Sci...237.1171S. doi:10.1126/science.2820055. ISSN 0036-8075. PMID 2820055.
7. Nicolls, Mark R.; Dixon, J. Brandon; Kitajewski, Jan; Peters-Golden, Marc; Voelkel, Norbert F.; Dhillon, Gundeep S.; Zamanian, Roham T.; Feroze, Abdullah H.; Nepiyushchikh, Zhanna (2017-05-10). "Leukotriene B4 antagonism ameliorates experimental lymphedema". Science Translational Medicine. 9 (389): eaal3920. doi:10.1126/scitranslmed.aal3920. ISSN 1946-6234. PMID 28490670.
8. Serhan, C. N.; Rouzer, C. A.; Lindgren, J. A.; Dahlen, S. E.; Samuelsson, B. (1987-09-04). "Leukotrienes and lipoxins: structures, biosynthesis, and biological effects". Science. 237 (4819): 1171–1176. Bibcode:1987Sci...237.1171S. doi:10.1126/science.2820055. ISSN 0036-8075. PMID 2820055.
9. O'Connor, J. Patrick; Lysz, Thomas (September 2008). "Celecoxib, NSAIDs and the skeleton". Drugs of Today. 44 (9): 693–709. doi:10.1358/dot.2008.44.9.1251573. ISSN 1699-3993. PMID 19137124.