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{{DISPLAYTITLE:Leukotriene A<sub>4</sub>}}
{{chembox
{{Chembox
| verifiedrevid = 396932507
|ImageFile=Leukotriene A4.svg | Name = Leukotriene A<sub>4</sub>
| Verifiedfields = changed
|ImageSize=
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|IUPACName=
| verifiedrevid = 428749275
|OtherNames=
| ImageFile = Leukotriene A4.svg
|Section1= {{Chembox Identifiers
| ImageSize =
| CASNo= 72059-45-1
| PIN = 4-<nowiki>{</nowiki>(2''S'',3''S'')-3-oxiran-2-yl}butanoic acid
| PubChem=5280383
| OtherNames =
| SMILES=
|Section1={{Chembox Identifiers
| MeSHName=Leukotriene+A4
| IUPHAR_ligand = 5214
}}
| Abbreviations = LTA<sub>4</sub>
|Section2= {{Chembox Properties
| CASNo_Ref = {{cascite|correct|??}}
| Formula=C<sub>20</sub>H<sub>30</sub>O<sub>3</sub>
| CASNo = 72059-45-1
| MolarMass=318.45 g/mol
| UNII_Ref = {{fdacite|correct|FDA}}
| Appearance=
| UNII = 7Y7MPZ6563
| Density=
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| PubChem = 5280383
| BoilingPt=
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
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| SMILES = CCCCC/C=C\C/C=C\C=C\C=C\1(O1)CCCC(=O)O
|Section3= {{Chembox Hazards
| 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
| MainHazards=
| InChIKey = UFPQIRYSPUYQHK-WAQVJNLQBZ
| FlashPt=
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| StdInChI = 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
}}
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = UFPQIRYSPUYQHK-WAQVJNLQSA-N
| RTECS =
| MeSHName = D017572
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 15651
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = C00909
}}
|Section2={{Chembox Properties
| C = 20 | H = 30 | O =3
| Appearance =
| Density =
| MeltingPt =
| MeltingPt_notes =
| BoilingPt =
| BoilingPt_notes =
| Solubility =
| SolubleOther =
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| LogP =
| VaporPressure =
| HenryConstant =
| AtmosphericOHRateConstant =
| pKa =
| pKb =
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|Section3={{Chembox Structure
| CrystalStruct =
| Coordination =
| MolShape =
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|Section4={{Chembox Thermochemistry
| DeltaHf =
| DeltaHc =
| Entropy =
| HeatCapacity =
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|Section5={{Chembox Pharmacology
| AdminRoutes =
| Bioavail =
| Metabolism =
| HalfLife =
| ProteinBound =
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| Legal_status =
| Legal_US =
| Legal_UK =
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| Pregnancy_AU =
| Pregnancy_US =
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|Section6={{Chembox Explosive
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| DetonationV =
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|Section7={{Chembox Hazards
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| NFPA-F =
| NFPA-R =
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|Section8={{Chembox Related
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}} }}
'''Leukotriene A4''' is a ].


'''Leukotriene A<sub>4</sub>''' ('''LTA<sub>4</sub>''') is a ], and is the precursor for the productions of ] (LTB<sub>4</sub>) and ] (LTC<sub>4</sub>).
] converts it to ].


== Biosynthesis ==
]
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 A<sub>4</sub>.<ref name= Abu >{{Cite journal |last1=Abu |first1=J.I. |last2=Konje |first2=J.C. |date=March 2000 |title=Leukotrienes in gynaecology: the hypothetical value of anti-leukotriene therapy in dysmenorrhoea and endometriosis |journal=Human Reproduction Update |volume=6 |issue=2 |pages=200–205 |issn=1355-4786 |pmid=10782578 |doi=10.1093/humupd/6.2.200 |doi-access=free}}</ref><ref name= Marx >{{Cite journal |last=Marx |first=J.L. |date=1982-03-12 |title=The leukotrienes in allergy and inflammation |journal=Science |volume=215 |issue=4538 |pages=1380–1383 |doi=10.1126/science.6278589 |issn=0036-8075 |pmid=6278589 |bibcode=1982Sci...215.1380M}}</ref> In this pathway, arachidonic acid is converted into ] (5-HPETE) as a result of a catalytic complex consisting of the enzyme ] (5-LO) and ] (FLAP) in the presence of ] and ].{{r|Abu|Marx}}<ref>{{Cite journal|last=Nicolls|first=Mark R.|last2=Voelkel|first2=Norbert F.|last3=Peters-Golden|first3=Marc|last4=Rajadas|first4=Jayakumar|last5=Fridlib|first5=Marina|last6=Inayathullah|first6=Mohammed|last7=Zamanian|first7=Roham T.|last8=Rabinovitch|first8=Marlene|last9=Farkas|first9=Laszlo|date=2013-08-28|title=Blocking Macrophage Leukotriene B4 Prevents Endothelial Injury and Reverses Pulmonary Hypertension|journal=Science Translational Medicine|volume=5|issue=200|pages=200ra117|doi=10.1126/scitranslmed.3006674|issn=1946-6234|pmid=23986401|pmc=4016764}}</ref> The resulting 5-HPETE yields the unstable allylic epoxide substrate LTA<sub>4</sub><ref name= Serhan >{{Cite journal |last1=Serhan |first1=C.N. |last2=Rouzer |first2=C.A. |last3=Lindgren |first3=J.A. |last4=Dahlen |first4=S.E. |last5=Samuelsson |first5=B. |date=1987-09-04 |title=Leukotrienes and lipoxins: structures, biosynthesis, and biological effects |journal=Science |volume=237 |issue=4819 |pages=1171–1176 |doi=10.1126/science.2820055 |issn=0036-8075 |pmid=2820055 |bibcode=1987Sci...237.1171S}}</ref> which is quickly hydrolyzed by the ] (LTA<sub>4</sub>H) enzyme to produce LTB<sub>4</sub>, or synthesized by ] (LTC<sub>4</sub>S) with the addition of glutathione to produce LTC<sub>4</sub> which can be further metabolized to produce ] (LTD<sub>4</sub>) and ] (LTE<sub>4</sub>).<ref>{{Cite journal|last=Nicolls|first=Mark R.|last2=Dixon|first2=J. Brandon|last3=Kitajewski|first3=Jan|last4=Peters-Golden|first4=Marc|last5=Voelkel|first5=Norbert F.|last6=Dhillon|first6=Gundeep S.|last7=Zamanian|first7=Roham T.|last8=Feroze|first8=Abdullah H.|last9=Nepiyushchikh|first9=Zhanna|date=2017-05-10|title=Leukotriene B4 antagonism ameliorates experimental lymphedema|journal=Science Translational Medicine|volume=9|issue=389|pages=eaal3920|doi=10.1126/scitranslmed.aal3920|issn=1946-6234|pmid=28490670|doi-access=free}}</ref>{{r|Serhan}} 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,<ref>{{Cite journal|last=O'Connor|first=J. Patrick|last2=Lysz|first2=Thomas|date=September 2008|title=Celecoxib, NSAIDs and the skeleton|journal=Drugs of Today|volume=44|issue=9|pages=693–709|doi=10.1358/dot.2008.44.9.1251573|issn=1699-3993|pmid=19137124}}</ref> but is the only pathway in which the subsequent steps will lead to the production of leukotrienes.


]
{{Leukotrienes}}


==References==
{{Reflist|2}}


{{Leukotrienes}}
{{Leukotrienergics}}


] ]


{{biochemistry-stub}}

]

Latest revision as of 17:04, 30 March 2024

Leukotriene A4
Names
Preferred IUPAC name 4-{(2S,3S)-3-oxiran-2-yl}butanoic acid
Identifiers
CAS Number
3D model (JSmol)
Abbreviations LTA4
ChEBI
ChemSpider
IUPHAR/BPS
KEGG
MeSH D017572
PubChem CID
UNII
CompTox Dashboard (EPA)
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/s1Key: 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/s1Key: UFPQIRYSPUYQHK-WAQVJNLQBZ
SMILES
  • CCCCC/C=C\C/C=C\C=C\C=C\1(O1)CCCC(=O)O
Properties
Chemical formula C20H30O3
Molar mass 318.457 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
Chemical compound

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

Biosynthesis

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. 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 5-lipoxygenase-activating protein (FLAP) in the presence of ATP and calcium ions. The resulting 5-HPETE yields the unstable allylic epoxide substrate LTA4 which is quickly hydrolyzed by the leukotriene A4 hydrolase (LTA4H) enzyme to produce LTB4, or synthesized by leukotriene C4 synthase (LTC4S) with the addition of glutathione to produce LTC4 which can be further metabolized to produce leukotriene D4 (LTD4) and leukotriene E4 (LTE4). 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, 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. 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.
  4. ^ 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.
  5. 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.
  6. 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.
Eicosanoids
Precursor
Prostanoids
Prostaglandins (PG)
Precursor
Active
D/J
E/F
I
Thromboxanes (TX)
Leukotrienes (LT)
Precursor
Initial
SRS-A
Eoxins (EX)
Precursor
Eoxins
Nonclassic
By function
Leukotriene signaling modulators
Receptor
(ligands)
BLTTooltip Leukotriene B4 receptor
BLT1Tooltip Leukotriene B4 receptor 1
BLT2Tooltip Leukotriene B4 receptor 2
CysLTTooltip Cysteinyl leukotriene receptor
CysLT1Tooltip Cysteinyl leukotriene receptor 1
CysLT2Tooltip Cysteinyl leukotriene receptor 2
CysLTETooltip Cysteinyl leukotriene receptor E
Enzyme
(inhibitors)
5-LOXTooltip Arachidonate 5-lipoxygenase
12-LOXTooltip Arachidonate 12-lipoxygenase
15-LOXTooltip Arachidonate 15-lipoxygenase
LTA4HTooltip Leukotriene A4 hydrolase
LTB4HTooltip Leukotriene B4 ω-hydroxylase
LTC4STooltip Leukotriene C4 synthase
LTC4HTooltip Leukotriene C4 hydrolase
LTD4Tooltip Leukotriene D4 hydrolase
Others
See also
Receptor/signaling modulators
Prostanoid signaling modulators
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