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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-05-22 15:12:31 UTC
Update Date2018-05-20 08:54:32 UTC
HMDB IDHMDB0003080
Secondary Accession Numbers
  • HMDB0005074
  • HMDB0062494
  • HMDB03080
  • HMDB05074
  • HMDB62494
Metabolite Identification
Common NameLeukotriene D4
DescriptionLeukotriene D4 (LTD4) is a cysteinyl leukotriene. Cysteinyl leukotrienes (CysLTs) are a family of potent inflammatory mediators that appear to contribute to the pathophysiologic features of allergic rhinitis. 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 beta-catenin through the CysLT1 receptor, PI3K (phosphoinositide 3-kinase), and GSK-3β (glycogen synthase kinase 3β). LTD4 induces beta-catenin translocation to the nucleus and activation of TCF/LEF family of transcription factors. LTD4 causes accumulation of free beta-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-3β 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 and are 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
(R-(R*,s*-(e,e,Z,Z)))-N-(S-(1-(4-carboxy-1-hydroxybutyl)-2,4,6,9-pentadecatetraenyl)-L-cysteinyl)glycineChEBI
5S-Hydroxy-6R-(S-cysteinylglycinyl)-7E,9E,11E,14Z-eicosatetraenoic acidChEBI
5S-Hydroxy-6R-(S-cysteinylglycinyl)-7E,9E,11E,14Z-eicosatetraenoateGenerator
Leukotriene DMeSH
Leukotriene D-4MeSH
Leukotrienes DMeSH
Leukotriene D 4MeSH
Chemical FormulaC25H40N2O6S
Average Molecular Weight496.66
Monoisotopic Molecular Weight496.26070819
IUPAC Name(5S,6R,7E,9E,11Z,14Z)-6-{[(2R)-2-amino-2-[(carboxymethyl)carbamoyl]ethyl]sulfanyl}-5-hydroxyicosa-7,9,11,14-tetraenoic acid
Traditional Nameleukotriene D4
CAS Registry Number73836-78-9
SMILES
CCCCC\C=C/C\C=C/C=C/C=C/[C@@H](SC[C@H](N)C(=O)NCC(O)=O)[C@@H](O)CCCC(O)=O
InChI Identifier
InChI=1S/C25H40N2O6S/c1-2-3-4-5-6-7-8-9-10-11-12-13-16-22(21(28)15-14-17-23(29)30)34-19-20(26)25(33)27-18-24(31)32/h6-7,9-13,16,20-22,28H,2-5,8,14-15,17-19,26H2,1H3,(H,27,33)(H,29,30)(H,31,32)/b7-6-,10-9-,12-11+,16-13+/t20-,21-,22+/m0/s1
InChI KeyYEESKJGWJFYOOK-IJHYULJSSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassEicosanoids
Direct ParentLeukotrienes
Alternative Parents
Substituents
  • 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 Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Biological role:

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 Solubility0.0026 g/LALOGPS
logP1.17ALOGPS
logP0.76ChemAxon
logS-5.3ALOGPS
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
Polarizability56.08 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
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, Positivesplash10-00ba-5203900000-020fb8d6f8e7819b95dbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-9202000000-c97059cae6f9b15bcf59View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00fr-9001000000-d0b5b22bf211a9204e69View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0f92-0304900000-60819ea0217759ba2a49View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0fai-2429100000-ca5e17f7b76919b96464View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0h93-4901000000-aa2c814d3b9e96a3371bView in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue Location
  • Intestine
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0258 +/- 0.00161 uMInfant (0-1 year old)Not SpecifiedNormal details
BloodDetected and Quantified0.000042 +/- 0.000004 uMAdult (>18 years old)Both
Normal
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00003987 +/- 0.00001591 uMInfant (0-1 year old)Not SpecifiedNormal details
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified<0.00001 uMInfant (0-1 year old)FemaleLeukotriene C4-Synthesis Deficiency details
Cerebrospinal Fluid (CSF)Detected and Quantified<0.00001 uMInfant (0-1 year old)FemaleLeukotriene C4-Synthesis Deficiency details
Associated Disorders and Diseases
Disease References
Leukotriene C4-Synthesis Deficiency
  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 ]
Associated OMIM IDs
  • 614037 (Leukotriene C4-Synthesis Deficiency)
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDC05951
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLeukotriene_D4
METLIN IDNot Available
PubChem Compound5280878
PDB IDNot Available
ChEBI ID28666
References
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 ]
  10. Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9. [PubMed:11413487 ]
  11. Watson AD: Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res. 2006 Oct;47(10):2101-11. Epub 2006 Aug 10. [PubMed:16902246 ]
  12. Sethi JK, Vidal-Puig AJ: Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. 2007 Jun;48(6):1253-62. Epub 2007 Mar 20. [PubMed:17374880 ]
  13. Lingwood D, Simons K: Lipid rafts as a membrane-organizing principle. Science. 2010 Jan 1;327(5961):46-50. doi: 10.1126/science.1174621. [PubMed:20044567 ]
  14. Gunstone, Frank D., John L. Harwood, and Albert J. Dijkstra (2007). The lipid handbook with CD-ROM. CRC Press.

Enzymes

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:
GGT1
Uniprot ID:
P19440
Molecular weight:
61409.67
Reactions
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:
GGT7
Uniprot ID:
Q9UJ14
Molecular weight:
70466.015
Reactions
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:
CYSLTR1
Uniprot ID:
Q9Y271
Molecular weight:
38540.5
General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Cleaves glutathione conjugates (By similarity).
Gene Name:
GGT6
Uniprot ID:
Q6P531
Molecular weight:
50508.83
Reactions
Leukotriene C4 + Amino acid → Leukotriene D4 + 5-L-Glutamyl amino aciddetails
General function:
Involved in gamma-glutamyltransferase activity
Specific function:
Not Available
Gene Name:
GGT7
Uniprot ID:
A0PJJ9
Molecular weight:
62565.3
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:
GGT5
Uniprot ID:
P36269
Molecular weight:
62331.75
Reactions
Leukotriene C4 + Amino acid → Leukotriene D4 + 5-L-Glutamyl amino aciddetails