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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:04:52 UTC
HMDB IDHMDB01509
Secondary Accession Numbers
  • 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
(5S,6Z,8E,10E,12R,14Z)-5,12,20-Trihydroxyicosa-6,8,10,14-tetraenoateGenerator
(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
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
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 KeyInChIKey=PTJFJXLGRSTECQ-PSPARDEHSA-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. 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
  • Long-chain fatty acid
  • Hydroxy fatty acid
  • Fatty acid
  • Unsaturated fatty acid
  • Secondary alcohol
  • Polyol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
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 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity104.91 m3·mol-1ChemAxon
Polarizability40.46 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
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
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Acetaminophen Action PathwaySMP00710Not Available
Acetylsalicylic Acid PathwaySMP00083Not Available
Antipyrine Action PathwaySMP00692Not Available
Antrafenine Action PathwaySMP00693Not Available
Arachidonic Acid MetabolismSMP00075map00590
Bromfenac PathwaySMP00102Not Available
Carprofen Action PathwaySMP00694Not Available
Celecoxib PathwaySMP00096Not Available
Diclofenac PathwaySMP00093Not Available
Diflunisal PathwaySMP00289Not Available
Etodolac PathwaySMP00084Not Available
Etoricoxib Action PathwaySMP00695Not Available
Fenoprofen Action PathwaySMP00696Not Available
Flurbiprofen Action PathwaySMP00697Not Available
Ibuprofen PathwaySMP00086Not Available
Indomethacin PathwaySMP00104Not Available
Ketoprofen PathwaySMP00085Not Available
Ketorolac PathwaySMP00098Not Available
Leukotriene C4 Synthesis DeficiencySMP00353Not Available
Lornoxicam Action PathwaySMP00700Not Available
Lumiracoxib Action PathwaySMP00699Not Available
Magnesium salicylate Action PathwaySMP00698Not Available
Mefanamic Acid PathwaySMP00109Not Available
Meloxicam PathwaySMP00106Not Available
Nabumetone PathwaySMP00114Not Available
Naproxen PathwaySMP00120Not Available
Nepafenac Action PathwaySMP00702Not Available
Oxaprozin PathwaySMP00113Not Available
Phenylbutazone Action PathwaySMP00701Not Available
Piroxicam PathwaySMP00077Not Available
Rofecoxib PathwaySMP00087Not Available
Salicylate-sodium Action PathwaySMP00708Not Available
Salicylic Acid Action PathwaySMP00709Not Available
Salsalate Action PathwaySMP00707Not Available
Sulindac PathwaySMP00094Not Available
Suprofen PathwaySMP00101Not Available
Tenoxicam Action PathwaySMP00706Not Available
Tiaprofenic Acid Action PathwaySMP00705Not Available
Tolmetin Action PathwaySMP00704Not Available
Trisalicylate-choline Action PathwaySMP00703Not Available
Valdecoxib PathwaySMP00116Not Available
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. [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
NuGOwiki LinkHMDB01509
Metagene LinkHMDB01509
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. [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. [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. [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. [11408337 ]
  5. Murphy RC, Gijon MA: Biosynthesis and metabolism of leukotrienes. Biochem J. 2007 Aug 1;405(3):379-95. [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. [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