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Record Information
Creation Date2006-05-22 15:12:25 UTC
Update Date2016-02-11 01:05:57 UTC
Secondary Accession NumbersNone
Metabolite Identification
Common Name12-Keto-tetrahydro-leukotriene B4
Description12-keto-tetrahydro-Leukotriene B4 is an inactivated enzymatic metabolite of leukotriene B4(LTB4), product of the human liver enzyme leukotriene B4 (LTB4) 12-hydroxydehydrogenase, also found in the porcine kidney and other mammals. LTB4 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. (PMID: 17623009 , 8394361 , 9667737 )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.
5S-Hydroxy-12-keto-6Z,8E-eicosadienoic acidHMDB
Chemical FormulaC20H34O4
Average Molecular Weight338.4816
Monoisotopic Molecular Weight338.245709576
IUPAC Name(5S,6Z,8E)-5-hydroxy-12-oxoicosa-6,8-dienoic acid
Traditional Nameleukotriene B
CAS Registry NumberNot Available
InChI Identifier
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
  • Leukotriene
  • Hydroxyeicosapolyenoic acid
  • Long-chain fatty acid
  • Keto fatty acid
  • Hydroxy fatty acid
  • Fatty acid
  • Unsaturated fatty acid
  • Secondary alcohol
  • Ketone
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
StatusExpected but not Quantified
  • Endogenous
  • Food
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
Experimental Properties
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP3.58Not Available
Predicted Properties
Water Solubility0.0067 mg/mLALOGPS
pKa (Strongest Acidic)4.58ChemAxon
pKa (Strongest Basic)-1.5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6 Å2ChemAxon
Rotatable Bond Count16ChemAxon
Refractivity99.88 m3·mol-1ChemAxon
Polarizability41.03 Å3ChemAxon
Number of Rings0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
SpectraNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid LocationsNot Available
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
Not Available
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 IDFDB023093
KNApSAcK IDNot Available
Chemspider ID4446246
KEGG Compound IDC02165
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB02995
Metagene LinkHMDB02995
METLIN IDNot Available
PubChem Compound5283122
PDB IDNot Available
ChEBI ID15647
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
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  2. Iversen L, Fogh K, Ziboh VA, Kristensen P, Schmedes A, Kragballe K: Leukotriene B4 formation during human neutrophil keratinocyte interactions: evidence for transformation of leukotriene A4 by putative keratinocyte leukotriene A4 hydrolase. J Invest Dermatol. 1993 Mar;100(3):293-8. [8382716 ]
  3. Mozalevskii AF, Travianko TD, Iakovlev AA, Smirnova EA, Novikova NP, Sapa IIu: [Content of arachidonic acid metabolites in blood and saliva of children with bronchial asthma] Ukr Biokhim Zh. 1997 Sep-Dec;69(5-6):162-8. [9606840 ]
  4. 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 ]
  5. Zijlstra FJ, Wilson JH: 15-HETE is the main eicosanoid present in mucus of ulcerative proctocolitis. Prostaglandins Leukot Essent Fatty Acids. 1991 May;43(1):55-9. [1652771 ]
  6. Depre M, Friedman B, Van Hecken A, de Lepeleire I, Tanaka W, Dallob A, Shingo S, Porras A, Lin C, de Schepper PJ: Pharmacokinetics and pharmacodynamics of multiple oral doses of MK-0591, a 5-lipoxygenase-activating protein inhibitor. Clin Pharmacol Ther. 1994 Jul;56(1):22-30. [8033491 ]
  7. Ko JK, Cho CH: Alcohol drinking and cigarette smoking: a "partner" for gastric ulceration. Zhonghua Yi Xue Za Zhi (Taipei). 2000 Dec;63(12):845-54. [11195134 ]
  8. Mohammadian P, Hummel T, Arora C, Carpenter T: Peripheral levels of inflammatory mediators in migraineurs during headache-free periods. Headache. 2001 Oct;41(9):867-72. [11703473 ]
  9. Ueno H, Mori T, Fujinaga T: Topical formulations and wound healing applications of chitosan. Adv Drug Deliv Rev. 2001 Nov 5;52(2):105-15. [11718934 ]
  10. Gambero A, Landucci EC, Toyama MH, Marangoni S, Giglio JR, Nader HB, Dietrich CP, De Nucci G, Antunes E: Human neutrophil migration in vitro induced by secretory phospholipases A2: a role for cell surface glycosaminoglycans. Biochem Pharmacol. 2002 Jan 1;63(1):65-72. [11754875 ]
  11. Labaudiniere R, Hendel W, Terlain B, Cavy F, Marquis O, Dereu N: omega-[(4-Phenyl-2-quinolyl)oxy]alkanoic acid derivatives: a new family of potent LTB4 antagonists. J Med Chem. 1992 Nov 13;35(23):4306-14. [1333011 ]
  12. Labaudiniere R, Dereu N, Cavy F, Guillet MC, Marquis O, Terlain B: omega-[(4,6-Diphenyl-2-pyridyl)oxy]alkanoic acid derivatives: a new family of potent and orally active LTB4 antagonists. J Med Chem. 1992 Nov 13;35(23):4315-24. [1333012 ]
  13. Costello PB, Baer AN, Green FA: Lipoxygenase products in inflammatory synovial fluids and other exudates. Ann Rheum Dis. 1992 Nov;51(11):1215-8. [1334643 ]
  14. Zsila F, Bikadi Z, Lockwood SF: In vitro binding of leukotriene B4 (LTB4) to human serum albumin: evidence from spectroscopic, molecular modeling, and competitive displacement studies. Bioorg Med Chem Lett. 2005 Aug 15;15(16):3725-31. [15993588 ]
  15. Bentancur AG, Naveh N, Lancri J, Selah BA, Shtrasburg S, Livneh A: Urine leukotriene B4 in familial Mediterranean fever and other forms of right lower abdominal pain. Acad Emerg Med. 2005 Jul;12(7):671-4. [15995103 ]
  16. Yan Y, Wang B, Zuo YG, Qu T: Inhibitory effects of mizolastine on ultraviolet B-induced leukotriene B4 production and 5-lipoxygenase expression in normal human dermal fibroblasts in vitro. Photochem Photobiol. 2006 May-Jun;82(3):665-9. [16402861 ]
  17. Elgebaly SA, Donshik PC, Rahhal F, Williams W: Neutrophil chemotactic factors in the tears of giant papillary conjunctivitis patients. Invest Ophthalmol Vis Sci. 1991 Jan;32(1):208-13. [1846131 ]
  18. Doyle MJ, Eichhold TH, Hynd BA, Weisman SM: Determination of leukotriene B4 in human plasma by gas chromatography using a mass selective detector and a stable isotope labelled internal standard. Effect of NE-11740 on arachidonic acid metabolism. J Pharm Biomed Anal. 1990;8(2):137-42. [1965571 ]
  19. Fujii I, Shingu M, Nobunaga M: Monocyte activation in early onset rheumatoid arthritis. Ann Rheum Dis. 1990 Jul;49(7):497-503. [2166487 ]
  20. Abayasekara DR, Kurlak LO, Jeremy JY, Dandona P, Sharpe RM, Cooke BA: The levels and possible involvement of leukotriene B4 and prostaglandin F2 alpha in the control of interstitial fluid volume in the rat testis. Int J Androl. 1990 Oct;13(5):408-18. [2178154 ]
  21. Mukhtar H, Bik DP, Ruzicka T, Merk HF, Bickers DR: Cytochrome P-450-dependent omega-oxidation of leukotriene B4 in rodent and human epidermis. J Invest Dermatol. 1989 Aug;93(2):231-5. [2474030 ]
  22. Merrill JE, Strom SR, Ellison GW, Myers LW: In vitro study of mediators of inflammation in multiple sclerosis. J Clin Immunol. 1989 Mar;9(2):84-96. [2541163 ]
  23. Hughes H, Mitchell JR, Gaskell SJ: Quantitation of leukotriene B4 in human serum by negative ion gas chromatography-mass spectrometry. Anal Biochem. 1989 Jun;179(2):304-8. [2549806 ]
  24. Johnson J, Meyrick B, Jesmok G, Brigham KL: Human recombinant tumor necrosis factor alpha infusion mimics endotoxemia in awake sheep. J Appl Physiol. 1989 Mar;66(3):1448-54. [2708260 ]
  25. Romero R, Quintero R, Emamian M, Wan M, Grzyboski C, Hobbins JC, Mitchell MD: Arachidonate lipoxygenase metabolites in amniotic fluid of women with intra-amniotic infection and preterm labor. Am J Obstet Gynecol. 1987 Dec;157(6):1454-60. [2827484 ]
  26. Dessein AJ, Lee TH, Elsas P, Ravalese J 3rd, Silberstein D, David JR, Austen KF, Lewis RA: Enhancement by monokines of leukotriene generation by human eosinophils and neutrophils stimulated with calcium ionophore A23187. J Immunol. 1986 May 15;136(10):3829-38. [3009610 ]
  27. Romero R, Emamian M, Wan M, Grzyboski C, Hobbins JC, Mitchell MD: Increased concentrations of arachidonic acid lipoxygenase metabolites in amniotic fluid during parturition. Obstet Gynecol. 1987 Dec;70(6):849-51. [3684118 ]
  28. Stenson WF, Lobos E: Sulfasalazine inhibits the synthesis of chemotactic lipids by neutrophils. J Clin Invest. 1982 Feb;69(2):494-7. [6120182 ]
  29. Klickstein LB, Shapleigh C, Goetzl EJ: Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic factors in synovial fluid and tissue in rheumatoid arthritis and spondyloarthritis. J Clin Invest. 1980 Nov;66(5):1166-70. [6253525 ]
  30. Leppert D, Hauser SL, Kishiyama JL, An S, Zeng L, Goetzl EJ: Stimulation of matrix metalloproteinase-dependent migration of T cells by eicosanoids. FASEB J. 1995 Nov;9(14):1473-81. [7589989 ]
  31. Shirazi Y, Rus HG, Macklin WB, Shin ML: Enhanced degradation of messenger RNA encoding myelin proteins by terminal complement complexes in oligodendrocytes. J Immunol. 1993 May 15;150(10):4581-90. [7683324 ]
  32. Dias VC, Shaffer EA, Wallace JL, Parsons HG: Bile salts determine leukotriene B4 synthesis in a human intestinal cell line (CaCo-2). Dig Dis Sci. 1994 Apr;39(4):802-8. [8149846 ]
  33. Matsuo M, Hamasaki Y, Masuyama T, Ohta M, Miyazaki S: Leukotriene B4 and C4 in cerebrospinal fluid from children with meningitis and febrile seizures. Pediatr Neurol. 1996 Feb;14(2):121-4. [8703223 ]
  34. Takamoto M, Yano T, Shintani T, Hiraku S: A highly sensitive and selective method for the determination of Leukotriene B4 in human plasma by negative ion chemical ionization/gas chromatography/tandem mass spectrometry. J Pharm Biomed Anal. 1995 Nov;13(12):1465-72. [8788131 ]
  35. Primiano T, Li Y, Kensler TW, Trush MA, Sutter TR: Identification of dithiolethione-inducible gene-1 as a leukotriene B4 12-hydroxydehydrogenase: implications for chemoprevention. Carcinogenesis. 1998 Jun;19(6):999-1005. [9667737 ]
  36. Murphy RC, Gijon MA: Biosynthesis and metabolism of leukotrienes. Biochem J. 2007 Aug 1;405(3):379-95. [17623009 ]
  37. Yokomizo T, Izumi T, Takahashi T, Kasama T, Kobayashi Y, Sato F, Taketani Y, Shimizu T: Enzymatic inactivation of leukotriene B4 by a novel enzyme found in the porcine kidney. Purification and properties of leukotriene B4 12-hydroxydehydrogenase. J Biol Chem. 1993 Aug 25;268(24):18128-35. [8394361 ]


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:
Uniprot ID:
Molecular weight:
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:
Uniprot ID:
Molecular weight:
General function:
Involved in binding
Specific function:
Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.
Gene Name:
Uniprot ID:
Molecular weight: