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Record Information
Version4.0
Creation Date2005-11-16 15:48:42 UTC
Update Date2017-09-27 08:24:07 UTC
HMDB IDHMDB0001509
Secondary Accession Numbers
  • HMDB01509
  • HMDB05092
Metabolite Identification
Common Name20-Hydroxy-leukotriene B4
Description20-hydroxy- Leukotriene B4 (20-OH-LTB4) is an omega-hydroxylated metabolite of leukotriene B4 in human neutrophils. Elevated urinary concentrations of 20-OH-LTB4 and LTB4 are found in patients with Sjogren-Larsson syndrome (SLS, OMIM 270220 ), an autosomal recessively inherited neurocutaneous disorder caused by a deficiency of the microsomal enzyme fatty aldehyde dehydrogenase (FALDH), which as an essential role in LTB4 metabolism. Preterm birth seems to be one of the features of the syndrome. The reason for the preterm birth is unclear. It is hypothesized that it relates to the defective LTB4 degradation in SLS. The pathological urinary excretion of LTB4 and 20-OH-LTB4 is a biochemical marker for SLS. Surprisingly, 20-OH-LTB4 concentrations are normal in CSF. Leukotriene B4 is the major metabolite in neutrophil polymorphonuclear leukocytes. Leukotrienes are metabolites of arachidonic acid derived from the action of 5-LO (5-lipoxygenase). The immediate product of 5-LO is LTA4 (leukotriene A4), which is enzymatically converted into either LTB4 (leukotriene B4) by LTA4 hydrolase or LTC4 (leukotriene C4) by LTC4 synthase. The regulation of leukotriene production occurs at various levels, including expression of 5-LO, translocation of 5-LO to the perinuclear region and phosphorylation to either enhance or inhibit the activity of 5-LO. Biologically active LTB4 is metabolized by w-oxidation carried out by specific cytochrome P450s (CYP4F) followed by beta-oxidation from the w-carboxy position and after CoA ester formation. Other specific pathways of leukotriene metabolism include the 12-hydroxydehydrogenase/ 15-oxo-prostaglandin-13-reductase that form a series of conjugated diene metabolites that have been observed to be excreted into human urine. Metabolism of LTC4 occurs by sequential peptide cleavage reactions involving a gamma-glutamyl transpeptidase that forms LTD4 (leukotriene D4) and a membrane-bound dipeptidase that converts LTD4 into LTE4 (leukotriene E4) before w-oxidation. These metabolic transformations of the primary leukotrienes are critical for termination of their biological activity, and defects in expression of participating enzymes may be involved in specific genetic disease. (PMID: 12709426 , 9799565 , 11408337 , 17623009 ). 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
(6Z,8E,10E,14Z)-(5S,12R)-5,12,20-Trihydroxyeicosa-6,8,10,14-tetraenoateChEBI
(6Z,8E,10E,14Z)-(5S,12R)-5,12,20-Trihydroxyicosa-6,8,10,14-tetraenoateChEBI
20-Hydroxy-LTB4ChEBI
20-OH-Leukotriene b4ChEBI
20-OH-LTB4ChEBI
(6Z,8E,10E,14Z)-(5S,12R)-5,12,20-Trihydroxyeicosa-6,8,10,14-tetraenoic acidGenerator
(6Z,8E,10E,14Z)-(5S,12R)-5,12,20-Trihydroxyicosa-6,8,10,14-tetraenoic acidGenerator
(5S,12R)-5,12,20-Trihydroxy-(6Z,8E,10E,14Z)-eicosatetraenoateHMDB
(5S,12R)-5,12,20-Trihydroxy-(6Z,8E,10E,14Z)-eicosatetraenoic acidHMDB
(5S,6Z,8E,10E,12R,14Z)-5,12,20-Trihydroxyicosa-6,8,10,14-tetraenoateHMDB
(5S,6Z,8E,10E,12R,14Z)-5,12,20-Trihydroxyicosa-6,8,10,14-tetraenoic acidHMDB
20-Hydroxy LTB4HMDB
20-Hydroxyleukotriene b4HMDB
20-OH-5S,12S-Dihydroxy-6,10-trans-8,14-cis-eicosatetraenoateHMDB
20-OH-5S,12S-Dihydroxy-6,10-trans-8,14-cis-eicosatetraenoic acidHMDB
5,12,20-THETEHMDB
5,12,20-TriHETEHMDB
5S,12R,20-Trihydroxy-6Z,8E,10E,14Z-eicosatetraenoateHMDB
5S,12R,20-Trihydroxy-6Z,8E,10E,14Z-eicosatetraenoic acidHMDB
Omega-hydroxy-LTB4HMDB
W-Hydroxy-LTB4HMDB
[S-[R*,s*-(e,Z,e,Z)]]-5,12,20-trihydroxy-6,8,10,14-eicosatetraenoateHMDB
[S-[R*,s*-(e,Z,e,Z)]]-5,12,20-trihydroxy-6,8,10,14-eicosatetraenoic acidHMDB
20-Hydroxy-leukotriene bMeSH
5,12,20-Trihydroxy-6,8,10,14-eicosatetraenoic acidMeSH
5,12,20-Trihydroxy-6,8,10,14-eicosatetraenoic acid, (S-(r*,s*-(e,Z,e,Z)))-isomerMeSH
Chemical FormulaC20H32O5
Average Molecular Weight352.4651
Monoisotopic Molecular Weight352.224974134
IUPAC Name(5S,6Z,8E,10E,12R,14Z)-5,12,20-trihydroxyicosa-6,8,10,14-tetraenoic acid
Traditional Name20-hydroxy-LTB4
CAS Registry Number79516-82-8
SMILES
OCCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O
InChI Identifier
InChI=1S/C20H32O5/c21-17-10-6-2-1-3-7-12-18(22)13-8-4-5-9-14-19(23)15-11-16-20(24)25/h3-5,7-9,13-14,18-19,21-23H,1-2,6,10-12,15-17H2,(H,24,25)/b5-4+,7-3-,13-8+,14-9-/t18-,19-/m1/s1
InChI KeyPTJFJXLGRSTECQ-PSPARDEHSA-N
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
Substituents
  • Leukotriene
  • Hydroxyeicosatetraenoic acid
  • Long-chain fatty acid
  • Hydroxy fatty acid
  • Fatty acid
  • Unsaturated fatty acid
  • Secondary alcohol
  • Carboxylic acid derivative
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Polyol
  • Hydrocarbon derivative
  • Organic oxide
  • Organic oxygen compound
  • Primary alcohol
  • Carbonyl group
  • Organooxygen compound
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Source:

  Biological:

    Animal:

Route of exposure:

  Enteral:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

    Cellular process:

    Chemical reaction:

    Biochemical process:

Role

Industrial application:

Biological role:

Physical Properties
StateLiquid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.033 g/LALOGPS
logP4.22ALOGPS
logP2.69ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)4.65ChemAxon
pKa (Strongest Basic)-1.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area97.99 ŲChemAxon
Rotatable Bond Count15ChemAxon
Refractivity104.91 m³·mol⁻¹ChemAxon
Polarizability40.46 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, PositiveNot AvailableView in JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (4 TMS) - 70eV, PositiveNot AvailableView in JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QIT , negativesplash10-0udi-0009000000-2b98c651c0cd0833ccefView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QIT , negativesplash10-0udi-0009000000-a681c9193735a4386b49View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QIT , negativesplash10-0udi-0009000000-8db36dce15edb0d7b2f3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QIT , negativesplash10-0udi-0109000000-e01ef44cb36e9df489f9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QIT , negativesplash10-0uea-0709000000-d7a7994b98cf3bfbe072View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QIT , negativesplash10-0f8b-0924000000-bb49aa4e02bfea5085c5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QIT , negativesplash10-0il1-0910000000-8f7913074625390c6208View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QIT , negativesplash10-0di9-0900000000-a87a75ca80ddc1745a1fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QIT , negativesplash10-0a4i-1900000000-972b13fd5c8b54c14aa2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00kr-0019000000-fed023a2c990a5c6753fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014r-1269000000-22fedd5f102230a634a7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00tp-6491000000-bfc9e7fd9147e861f375View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009000000-e84044e33fbc237fabfcView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0uei-1129000000-f307e44b0f4e538946e7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-9341000000-49f0ced38039afa26a80View in MoNA
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
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
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified<0.0001 uMAdult (>18 years old)Both
Normal
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000075 (0.0 - 0.000015) uMChildren (1-13 years old)BothNormal details
UrineDetected and Quantified0.0000025 (0.0 - 0.000005) umol/mmol creatinineChildren (1-13 years old)Not SpecifiedNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
UrineDetected and Quantified0.0003 +/- 0.00014 umol/mmol creatinineChildren (1-13 years old)Not SpecifiedSjögren-Larsson syndrome details
Associated Disorders and Diseases
Disease References
Sjögren-Larsson syndrome
  1. Willemsen MA, Rotteveel JJ, de Jong JG, Wanders RJ, IJlst L, Hoffmann GF, Mayatepek E: Defective metabolism of leukotriene B4 in the Sjogren-Larsson syndrome. J Neurol Sci. 2001 Jan 15;183(1):61-7. [PubMed:11166796 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022663
KNApSAcK IDNot Available
Chemspider ID4444320
KEGG Compound IDC04853
BioCyc ID20-OH-LTB4
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN ID6287
PubChem Compound5280745
PDB IDNot Available
ChEBI ID15646
References
Synthesis ReferenceZamboni, Robert; Rokach, Joshua. Stereospecific synthesis of two metabolites of LTB4. Tetrahedron Letters (1982), 23(46), 4751-4.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Berry KA, Borgeat P, Gosselin J, Flamand L, Murphy RC: Urinary metabolites of leukotriene B4 in the human subject. J Biol Chem. 2003 Jul 4;278(27):24449-60. Epub 2003 Apr 22. [PubMed:12709426 ]
  2. Willemsen MA, Rotteveel JJ, de Jong JG, Wanders RJ, IJlst L, Hoffmann GF, Mayatepek E: Defective metabolism of leukotriene B4 in the Sjogren-Larsson syndrome. J Neurol Sci. 2001 Jan 15;183(1):61-7. [PubMed:11166796 ]
  3. Goldman DW, Olson DM, Payan DG, Gifford LA, Goetzl EJ: Development of receptors for leukotriene B4 on HL-60 cells induced to differentiate by 1 alpha,25-dihydroxyvitamin D3. J Immunol. 1986 Jun 15;136(12):4631-6. [PubMed:3011899 ]
  4. Willemsen MA, IJlst L, Steijlen PM, Rotteveel JJ, de Jong JG, van Domburg PH, Mayatepek E, Gabreels FJ, Wanders RJ: Clinical, biochemical and molecular genetic characteristics of 19 patients with the Sjogren-Larsson syndrome. Brain. 2001 Jul;124(Pt 7):1426-37. [PubMed:11408337 ]
  5. Murphy RC, Gijon MA: Biosynthesis and metabolism of leukotrienes. Biochem J. 2007 Aug 1;405(3):379-95. [PubMed:17623009 ]
  6. Jin R, Koop DR, Raucy JL, Lasker JM: Role of human CYP4F2 in hepatic catabolism of the proinflammatory agent leukotriene B4. Arch Biochem Biophys. 1998 Nov 1;359(1):89-98. [PubMed:9799565 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP4F2
Uniprot ID:
P78329
Molecular weight:
59852.825
Reactions
Leukotriene B4 + NADPH + Oxygen → 20-Hydroxy-leukotriene B4 + NADP + Waterdetails
Leukotriene B4 + NADPH + Hydrogen Ion + Oxygen → 20-Hydroxy-leukotriene B4 + NADP + Waterdetails
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. This enzyme requires molecular oxygen and NADPH for the omega-hydroxylation of LTB4, a potent chemoattractant for polymorphonuclear leukocytes.
Gene Name:
CYP4F3
Uniprot ID:
Q08477
Molecular weight:
59846.085
Reactions
Leukotriene B4 + NADPH + Oxygen → 20-Hydroxy-leukotriene B4 + NADP + Waterdetails
Leukotriene B4 + NADPH + Hydrogen Ion + Oxygen → 20-Hydroxy-leukotriene B4 + NADP + Waterdetails
General function:
Secondary metabolites biosynthesis, transport and catabolism
Specific function:
Not Available
Gene Name:
CYP4F11
Uniprot ID:
Q9HBI6
Molecular weight:
60145.165
Reactions
Leukotriene B4 + NADPH + Hydrogen Ion + Oxygen → 20-Hydroxy-leukotriene B4 + NADP + Waterdetails
General function:
Secondary metabolites biosynthesis, transport and catabolism
Specific function:
Hydroxylates arachidonic acid (20:4n-6) to (18R)-hydroxyarachidonate. Shows little activity against prostaglandin (PG) D2, PGE1, PGE2, PGF2alpha, and leukotriene B4. Catalyzes omega-2 and omega-3-hydroxylation of PGH1 and PGH2. Catalyzes epoxidation of 4,7,10,13,16,19-(Z)-docosahexaenoic acid (22:6n-3) and 7,10,13,16,19-(Z)-docosapentaenoic acid (22:5n-3) and omega-3-hydroxylation of 4,7,10,13,16-(Z)-docosapentaenoic acid (22:5n-6). Catalyzes hydroxylation of PGI2 and carbaprostacyclin.
Gene Name:
CYP4F8
Uniprot ID:
P98187
Molecular weight:
59993.995
Reactions
Leukotriene B4 + NADPH + Hydrogen Ion + Oxygen → 20-Hydroxy-leukotriene B4 + NADP + Waterdetails
General function:
Involved in monooxygenase activity
Specific function:
Not Available
Gene Name:
CYP4F22
Uniprot ID:
Q6NT55
Molecular weight:
Not Available
Reactions
Leukotriene B4 + NADPH + Hydrogen Ion + Oxygen → 20-Hydroxy-leukotriene B4 + NADP + Waterdetails