You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
StatusDetected and Quantified
Creation Date2006-05-22 15:12:31 UTC
Update Date2017-12-07 01:50:22 UTC
Secondary Accession Numbers
  • HMDB03080
  • HMDB05074
Metabolite Identification
Common NameLeukotriene D4
DescriptionLeukotriene D4 (LTD4) is a cysteinyl leukotriene a family of potent inflammatory mediators. LTD4 is a pro-inflammatory mediator known to mediate its effects through specific cell-surface receptors belonging to the G-protein-coupled receptor family, namely the high-affinity CysLT1 (cysteinyl leukotriene 1) receptor. LTD4 is present at high levels in many inflammatory conditions, and areas of chronic inflammation have an increased risk for subsequent cancer development; LTD4 is associated with the pathogenesis of several inflammatory disorders, such as asthma and inflammatory bowel disease. Exposure to LTD4 increases survival and proliferation in intestinal epithelial cells. CysLT1 regulator is up-regulated in colon cancer tissue and LTD4 signalling facilitates the survival of cancer cells. LTD4 could reduce apoptosis in non-transformed epithelial cells. LTD4 causes up-regulation of b-catenin through the CysLT1 receptor, PI3K (phosphoinositide 3-kinase) and GSK-3b (glycogen synthase kinase 3b). LTD4 induces b-catenin translocation to the nucleus and activation of TCF/LEF family of transcription factors. LTD4 causes accumulation of free b-catenin in non-transformed intestinal epithelial cells through the CysLT1 receptor, and this accumulation is dependent upon the activation of PI3K as well as GSK-3b inactivation. (PMID: 16042577 , 12607939 ). 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.
Leukotriene DHMDB
Leukotrienes DMeSH
Leukotriene D-4MeSH
Leukotriene D 4MeSH
Chemical FormulaC25H40N2O6S
Average Molecular Weight496.66
Monoisotopic Molecular Weight496.260707712
IUPAC Name(5S,6R,7E,9E,11Z,14Z)-6-({2-amino-2-[(carboxymethyl)carbamoyl]ethyl}sulfanyl)-5-hydroxyicosa-7,9,11,14-tetraenoic acid
Traditional Nameleukotriene D4
CAS Registry Number73836-78-9
InChI Identifier
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as leukotrienes. These are eicosanoids containing a hydroxyl group attached to the aliphatic chain of an arachidonic acid. Leukotrienes have four double bonds, three (and only three) of which are conjugated.
KingdomChemical entities
Super ClassOrganic compounds
ClassLipids and lipid-like molecules
Sub ClassFatty Acyls
Direct ParentLeukotrienes
Alternative Parents
  • Leukotriene
  • Hydroxyeicosatetraenoic acid
  • Alpha-dipeptide
  • Alpha peptide
  • Long-chain fatty acid
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Alpha-amino acid amide
  • Cysteine or derivatives
  • Alpha-amino acid or derivatives
  • Hydroxy fatty acid
  • Thia fatty acid
  • Dicarboxylic acid or derivatives
  • Fatty acid
  • Unsaturated fatty acid
  • Secondary alcohol
  • Secondary carboxylic acid amide
  • Amino acid
  • Carboxamide group
  • Amino acid or derivatives
  • Carboxylic acid derivative
  • Carboxylic acid
  • Dialkylthioether
  • Sulfenyl compound
  • Thioether
  • Amine
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Alcohol
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Primary amine
  • Primary aliphatic amine
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available

Biological Location:


  Biofluid and excreta:

  Organ and components:




Route of exposure:



Naturally occurring process:

  Biological process:

    Biochemical pathway:

    Chemical reaction:

    Biochemical process:

    Cellular process:


Biological role:

Physical Properties
Experimental Properties
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
Water Solubility0.0026 g/LALOGPS
pKa (Strongest Acidic)3.29ChemAxon
pKa (Strongest Basic)8.05ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area149.95 ŲChemAxon
Rotatable Bond Count20ChemAxon
Refractivity140.42 m³·mol⁻¹ChemAxon
Polarizability56.16 ųChemAxon
Number of Rings0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-002f-8318900000-91190bec2dc8a7c28c8bView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00bl-9222555000-5956dd7aa924eaaf2c69View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-1103900000-bc4dd0f12e84be630db1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0550-8629300000-341e78476590a95b3affView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-9135000000-40d902c9bf62503e9eafView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0f9t-0203900000-889c8aed5a2a2198f2baView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0fai-2429100000-b9a20a4b0fb6624f7cfbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00di-6911000000-446fa2442a9bd57788beView in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Biofluid Locations
  • Blood
Tissue Location
  • Intestine
Arachidonic Acid MetabolismPw000044Pw000044 greyscalePw000044 simpleMap00590
Normal Concentrations
BloodDetected and Quantified0.000042 +/- 0.000004 uMAdult (>18 years old)Both
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 IDFDB023105
KNApSAcK IDNot Available
Chemspider ID4940074
KEGG Compound IDC05951
BioCyc IDCPD66-21
BiGG ID47032
Wikipedia LinkLeukotriene D4
PubChem Compound6435286
PDB IDNot Available
ChEBI ID1044940
Synthesis ReferenceCorey, E. J.; Clark, David A.; Marfat, Anthony; Goto, Giichi. Total synthesis of slow reacting substances (SRS). "Leukotriene C-2" (11-trans-leukotriene C) and leukotriene D. Tetrahedron Letters (1980), 21(33), 3143-6.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Mayatepek E, Flock B: Leukotriene C4-synthesis deficiency: a new inborn error of metabolism linked to a fatal developmental syndrome. Lancet. 1998 Nov 7;352(9139):1514-7. [PubMed:9820300 ]
  2. Beckh K, Dirks A, Koop I, Koop H, Adler G: Impairment of hepatic transport processes in perfused rat liver by the specific CCK receptor antagonist loxiglumide. Res Exp Med (Berl). 1997;197(3):125-35. [PubMed:9406280 ]
  3. Card GL, Li Y, Miller S, Wright BE: Carbonate inhibition of leukotriene D4-dipeptidase in human serum. Prostaglandins Leukot Essent Fatty Acids. 1992 Dec;47(4):301-5. [PubMed:1492107 ]
  4. Card GL, Unnithan T, Rhodes MJ, Wright BE: Leukotriene metabolism and hypersensitivity in man and mouse. Biochem Biophys Res Commun. 1989 Oct 31;164(2):626-30. [PubMed:2573348 ]
  5. Hsieh JY, Lin C, Matuszewski BK: Robotic sample preparation and high-performance liquid chromatographic analysis of verlukast in human plasma. J Chromatogr B Biomed Appl. 1994 Nov 18;661(2):307-12. [PubMed:7894671 ]
  6. Adolfsson JL, Ohd JF, Sjolander A: Leukotriene D4-induced activation and translocation of the G-protein alpha i3-subunit in human epithelial cells. Biochem Biophys Res Commun. 1996 Sep 13;226(2):413-9. [PubMed:8806649 ]
  7. Amin RD, Cheng H, Rogers JD: Determination of MK-0476 in human plasma by liquid chromatography. J Pharm Biomed Anal. 1995 Feb;13(2):155-8. [PubMed:7766722 ]
  8. Mizutani N: [Studies on the experimental allergic rhinitis induced by Japanese cedar pollen--role of cysteinyl leukotrienes in nasal allergic symptoms]. Yakugaku Zasshi. 2003 Jan;123(1):1-8. [PubMed:12607939 ]
  9. Mezhybovska M, Wikstrom K, Ohd JF, Sjolander A: Pro-inflammatory mediator leukotriene D4 induces transcriptional activity of potentially oncogenic genes. Biochem Soc Trans. 2005 Aug;33(Pt 4):698-700. [PubMed:16042577 ]


General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Initiates extracellular glutathione (GSH) breakdown, provides cells with a local cysteine supply and contributes to maintain intracellular GSH level. It is part of the cell antioxidant defense mechanism. Catalyzes the transfer of the glutamyl moiety of glutathione to amino acids and dipeptide acceptors. Alternatively, glutathione can be hydrolyzed to give Cys-Gly and gamma glutamate. Isoform 3 seems to be inactive.
Gene Name:
Uniprot ID:
Molecular weight:
Leukotriene C4 + Amino acid → Leukotriene D4 + 5-L-Glutamyl amino aciddetails
General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Cleaves glutathione conjugates (By similarity).
Gene Name:
Uniprot ID:
Molecular weight:
Leukotriene C4 + Amino acid → Leukotriene D4 + 5-L-Glutamyl amino aciddetails
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Receptor for cysteinyl leukotrienes mediating bronchoconstriction of individuals with and without asthma. Stimulation by LTD4 results in the contraction and proliferation of smooth muscle, edema, eosinophil migration and damage to the mucus layer in the lung. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTD4 >> LTE4 = LTC4 >> LTB4
Gene Name:
Uniprot ID:
Molecular weight:
General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Cleaves glutathione conjugates (By similarity).
Gene Name:
Uniprot ID:
Molecular weight:
Leukotriene C4 + Amino acid → Leukotriene D4 + 5-L-Glutamyl amino aciddetails
General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Not Available
Gene Name:
Uniprot ID:
Molecular weight:
General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Cleaves the gamma-glutamyl peptide bond of glutathione conjugates, but maybe not glutathione itself. Converts leukotriene C4 (LTC4) to leukotriene D4 (LTD4).
Gene Name:
Uniprot ID:
Molecular weight:
Leukotriene C4 + Amino acid → Leukotriene D4 + 5-L-Glutamyl amino aciddetails