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Record Information
Version3.6
Creation Date2006-05-22 15:12:31 UTC
Update Date2013-05-29 19:37:21 UTC
HMDB IDHMDB03080
Secondary Accession Numbers
  • 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.
Structure
Thumb
Synonyms
  1. (R-(R*,S*-(E,E,Z,Z)))-N-(S-(1-(4-carboxy-1-hydroxybutyl)-2,4,6,9-pentadecatetraenyl)-L-cysteinyl)-glycine
  2. Leukotriene D
  3. LTD
  4. LTD4
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 Name(5S,6R,7E,9E,11Z,14Z)-6-{[2-amino-2-(carboxymethylcarbamoyl)ethyl]sulfanyl}-5-hydroxyicosa-7,9,11,14-tetraenoic acid
CAS Registry Number73836-78-9
SMILES
CCCCC\C=C/C\C=C/C=C/C=C/[C@@H](SCC(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-LDDGIIIKSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassPeptides
Sub ClassN/A
Other Descriptors
  • Aliphatic Acyclic Compounds
  • Hydroxy Fatty Acids
  • Leukotrienes
  • Organic Compounds
  • Thia Fatty Acids
  • Unsaturated Fatty Acids
Substituents
  • Acyclic Alkene
  • Carboxamide Group
  • Carboxylic Acid
  • Dicarboxylic Acid Derivative
  • Hydroxyeicosatetraenoic Acid
  • N Acyl Alpha Amino Acid
  • N Acylglycine
  • N Substituted Alpha Amino Acid
  • Primary Aliphatic Amine (Alkylamine)
  • Secondary Alcohol
  • Secondary Carboxylic Acid Amide
  • Thioether
Direct ParentPeptides
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • 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 Solubility0.0026 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 Area149.95ChemAxon
Rotatable Bond Count20ChemAxon
Refractivity140.42ChemAxon
Polarizability56.16ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane (predicted from logP)
  • Endoplasmic reticulum
Biofluid Locations
  • Blood
Tissue Location
  • Intestine
Pathways
NameSMPDB LinkKEGG Link
Arachidonic Acid MetabolismSMP00075map00590
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.000042 +/- 0.000004 uMAdult (>18 years old)Not Specified
Normal
details
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 ID20-HYDROXY-LEUKOTRIENE-E4
BiGG ID47032
Wikipedia LinkLeukotriene D4
NuGOwiki LinkHMDB03080
Metagene LinkHMDB03080
METLIN ID3583
PubChem Compound6435286
PDB IDNot Available
ChEBI ID1044940
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

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