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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-09-14 00:08:17 UTC
HMDB IDHMDB0001337
Secondary Accession Numbers
  • HMDB01337
Metabolite Identification
Common NameLeukotriene A4
DescriptionLeukotriene A4 (LTA4) is the first metabolite in the series of reactions leading to the synthesis of all leukotrienes. 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid to LTA4.The first step consists of the oxidation of arachidonic acid to the unstable intermediate 5-hydroperoxyeicosatetraenoic acid (5-HPETE), and the second step is the dehydration of 5-HPETE to form LTA4. Leukotriene A4, an unstable epoxide, is hydrolyzed to leukotriene B4 or conjugated with glutathione to yield leukotriene C4 and its metabolites, leukotriene D4 and leukotriene E4. The leukotrienes participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. Recent studies also suggest a neuroendocrine role for leukotriene C4 in luteinizing hormone secretion. (PMID: 10591081 , 2820055 ). Leukotrienes are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes) and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent, able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis, through receptor-mediated G-protein linked signaling pathways.
Structure
Thumb
Synonyms
ValueSource
(5S,6S,7E,9E,11Z,14Z)-5,6-Epoxyicosa-7,9,11,14-tetraenoateChEBI
(7E,9E,11Z,14Z)-(5S,6S)-5,6-Epoxyeicosa-7,9,11,14-tetraenoateChEBI
(7E,9E,11Z,14Z)-(5S,6S)-5,6-Epoxyeicosa-7,9,11,14-tetraenoic acidChEBI
(7E,9E,11Z,14Z)-(5S,6S)-5,6-Epoxyicosa-7,9,11,14-tetraenoateChEBI
5(S)-5,6-oxido-7,9-trans-11,14-cis-Eicosatetraenoic acidChEBI
5S,6S-Epoxy-7E,9E,11Z,14Z-eicosatetraenoic acidChEBI
5S,6S-Leukotriene a4ChEBI
LTA4ChEBI
(5S,6S,7E,9E,11Z,14Z)-5,6-Epoxyicosa-7,9,11,14-tetraenoic acidGenerator
(7E,9E,11Z,14Z)-(5S,6S)-5,6-Epoxyicosa-7,9,11,14-tetraenoic acidGenerator
5(S)-5,6-oxido-7,9-trans-11,14-cis-EicosatetraenoateGenerator
5S,6S-Epoxy-7E,9E,11Z,14Z-eicosatetraenoateGenerator
(7E,9E,11Z,14Z)-(5S,6S)-5,6-Epoxyicosa- 7,9,11,14-tetraenoateHMDB
(7E,9E,11Z,14Z)-(5S,6S)-5,6-Epoxyicosa- 7,9,11,14-tetraenoic acidHMDB
(7E,9E,11Z,14Z)-(5S,6S)-5,6-Epoxyicosa-7,9,11,14-tetrenoioc acidHMDB
Leukotriene aMeSH
Leukotriene a 4MeSH
Leukotrienes aMeSH
Leukotriene a-4MeSH
Chemical FormulaC20H30O3
Average Molecular Weight318.4504
Monoisotopic Molecular Weight318.219494826
IUPAC Name4-[(2S,3S)-3-[(1E,3E,5Z,8Z)-tetradeca-1,3,5,8-tetraen-1-yl]oxiran-2-yl]butanoic acid
Traditional Nameleukotriene A4
CAS Registry Number72059-45-1
SMILES
CCCCC\C=C/C\C=C/C=C/C=C/[C@@H]1O[C@H]1CCCC(O)=O
InChI Identifier
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
InChI KeyUFPQIRYSPUYQHK-WAQVJNLQSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as epoxy fatty acids. These are fatty acids containing an oxirane ring as part of the aliphatic chain.
KingdomChemical entities
Super ClassOrganic compounds
ClassLipids and lipid-like molecules
Sub ClassFatty Acyls
Direct ParentEpoxy fatty acids
Alternative Parents
Substituents
  • Epoxy fatty acid
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Oxirane
  • Dialkyl ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Component of Prostaglandin and leukotriene metabolism
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.000424 mg/mLALOGPS
logP6.04ALOGPS
logP5.44ChemAxon
logS-5.9ALOGPS
pKa (Strongest Acidic)4.49ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area49.83 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity99.32 m3·mol-1ChemAxon
Polarizability37.95 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Biofluid LocationsNot Available
Tissue Location
  • Epidermis
Pathways
Acetaminophen Action PathwayPw000687Pw000687 greyscalePw000687 simpleNot Available
Acetylsalicylic Acid PathwayPw000128Pw000128 greyscalePw000128 simpleNot Available
Antipyrine Action PathwayPw000669Pw000669 greyscalePw000669 simpleNot Available
Antrafenine Action PathwayPw000670Pw000670 greyscalePw000670 simpleNot Available
Arachidonic Acid MetabolismPw000044Pw000044 greyscalePw000044 simpleMap00590
Displaying entries 1 - 5 of 41 in total
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022561
KNApSAcK IDNot Available
Chemspider ID4444074
KEGG Compound IDC00909
BioCyc IDCPD-8892
BiGG ID36355
Wikipedia LinkLeukotriene A4
NuGOwiki LinkHMDB0001337
METLIN ID3449
PubChem Compound5280383
PDB IDNot Available
ChEBI ID15651
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Iversen L, Fogh K, Ziboh VA, Kristensen P, Schmedes A, Kragballe K: Leukotriene B4 formation during human neutrophil keratinocyte interactions: evidence for transformation of leukotriene A4 by putative keratinocyte leukotriene A4 hydrolase. J Invest Dermatol. 1993 Mar;100(3):293-8. [PubMed:8382716 ]
  2. Luscinskas FW, Nicolaou KC, Webber SE, Veale CA, Gimbrone MA Jr, Serhan CN: Ca2+ mobilization with leukotriene A4 and epoxytetraenes in human neutrophils. Biochem Pharmacol. 1990 Jan 15;39(2):355-65. [PubMed:2154229 ]
  3. MacMillan DK, Hill E, Sala A, Sigal E, Shuman T, Henson PM, Murphy RC: Eosinophil 15-lipoxygenase is a leukotriene A4 synthase. J Biol Chem. 1994 Oct 28;269(43):26663-8. [PubMed:7929400 ]
  4. Iversen L, Ziboh VA, Shimizu T, Ohishi N, Radmark O, Wetterholm A, Kragballe K: Identification and subcellular localization of leukotriene A4-hydrolase activity in human epidermis. J Dermatol Sci. 1994 Jun;7(3):191-201. [PubMed:7918238 ]
  5. Nicholson DW, Klemba MW, Rasper DM, Metters KM, Zamboni RJ, Ford-Hutchinson AW: Purification of human leukotriene C4 synthase from dimethylsulfoxide-differentiated U937 cells. Eur J Biochem. 1992 Oct 15;209(2):725-34. [PubMed:1425677 ]
  6. Silverman ES, Drazen JM: The biology of 5-lipoxygenase: function, structure, and regulatory mechanisms. Proc Assoc Am Physicians. 1999 Nov-Dec;111(6):525-36. [PubMed:10591081 ]
  7. Samuelsson B, Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN: Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science. 1987 Sep 4;237(4819):1171-6. [PubMed:2820055 ]

Enzymes

General function:
Involved in enzyme activator activity
Specific function:
Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4.
Gene Name:
LTC4S
Uniprot ID:
Q16873
Molecular weight:
16566.465
Reactions
Leukotriene A4 + Glutathione → Leukotriene C4details
General function:
Involved in metal ion binding
Specific function:
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:
ALOX5
Uniprot ID:
P09917
Molecular weight:
77982.595
Reactions
5(S)-Hydroperoxyeicosatetraenoic acid → Leukotriene A4 + Waterdetails
Arachidonic acid + Oxygen → Leukotriene A4 + Waterdetails
General function:
Involved in binding
Specific function:
Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.
Gene Name:
LTA4H
Uniprot ID:
P09960
Molecular weight:
69284.64
Reactions
Leukotriene A4 + Water → Leukotriene B4details