Leukotriene metabolic pathway (Homo sapiens)

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ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none LTC4 synthasedeficiency12-Oxo-LTB420-hydroxy-LTE4Other reactome pathways needed?LTA4HLTA4(C2)-COOH-LTELTC4LTE420-carboxy-LTE420-hydroxy-LTB4GlutathioneArachidonic acid16-carboxy-LTB4N-acetyl-LTE4LTD4PTGR120-COOH-LTB418-carboxy-LTE4GGT5ABCC1???CYP4F35-LOAP5-LO20-oxo-LTB4(C2)-COOH-LTB5-HPETELTC4S5-LOleukotriene-E4 20-monooxygenase18-COOH-LTB4DPEP1?16-carboxy-LTE4LTB4GGT1GlutathionuriaCysteinylglycinasedeficiencyDPEP2LTC4Name: Metabolic pathway leukotrieneOrganism: Homo sapiens


Description

metabolic pathway leuktoriene

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Quality Tags

Image:Curated.pngReview changes for Approved
Image:Wplogo_31.pngCommunity: Inborn Errors of Metabolism (IEM)
Image:MissingXref.pngAnnotate nodes
Image:Wplogo_31.pngCommunity: Rare Diseases

Ontology Terms

Bibliography

View all...
  1. Wheelan P, Hankin JA, Bilir B, Guenette D, Murphy RC; ''Metabolic transformations of leukotriene B4 in primary cultures of human hepatocytes.''; J Pharmacol Exp Ther, 1999 PubMed Europe PMC Scholia
  2. Welsch DJ, Creely DP, Hauser SD, Mathis KJ, Krivi GG, Isakson PC; ''Molecular cloning and expression of human leukotriene-C4 synthase.''; Proc Natl Acad Sci U S A, 1994 PubMed Europe PMC Scholia
  3. Lam BK, Owen WF Jr, Austen KF, Soberman RJ; ''The identification of a distinct export step following the biosynthesis of leukotriene C4 by human eosinophils.''; J Biol Chem, 1989 PubMed Europe PMC Scholia
  4. Wickham S, West MB, Cook PF, Hanigan MH; ''Gamma-glutamyl compounds: substrate specificity of gamma-glutamyl transpeptidase enzymes.''; Anal Biochem, 2011 PubMed Europe PMC Scholia
  5. Kikuta Y, Kusunose E, Kondo T, Yamamoto S, Kinoshita H, Kusunose M; ''Cloning and expression of a novel form of leukotriene B4 omega-hydroxylase from human liver.''; FEBS Lett, 1994 PubMed Europe PMC Scholia
  6. De Carolis E, Denis D, Riendeau D; ''Oxidative inactivation of human 5-lipoxygenase in phosphatidylcholine vesicles.''; Eur J Biochem, 1996 PubMed Europe PMC Scholia
  7. Lee CW, Lewis RA, Corey EJ, Austen KF; ''Conversion of leukotriene D4 to leukotriene E4 by a dipeptidase released from the specific granule of human polymorphonuclear leucocytes.''; Immunology, 1983 PubMed Europe PMC Scholia
  8. Mesa J, Alsina C, Oppermann U, Parés X, Farrés J, Porté S; ''Human prostaglandin reductase 1 (PGR1): Substrate specificity, inhibitor analysis and site-directed mutagenesis.''; Chem Biol Interact, 2015 PubMed Europe PMC Scholia
  9. Petrich K, Ludwig P, Kühn H, Schewe T; ''The suppression of 5-lipoxygenation of arachidonic acid in human polymorphonuclear leucocytes by the 15-lipoxygenase product (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid: structure-activity relationship and mechanism of action.''; Biochem J, 1996 PubMed Europe PMC Scholia
  10. Ivanov I, Golovanov AB, Ferretti C, Canyelles-Niño M, Heydeck D, Stehling S, Lluch JM, González-Lafont À, Kühn H; ''Mutations of Triad Determinants Changes the Substrate Alignment at the Catalytic Center of Human ALOX5.''; ACS Chem Biol, 2019 PubMed Europe PMC Scholia
  11. Sala A, Voelkel N, Maclouf J, Murphy RC; ''Leukotriene E4 elimination and metabolism in normal human subjects.''; J Biol Chem, 1990 PubMed Europe PMC Scholia
  12. Odlander B, Claesson HE, Bergman T, Rådmark O, Jörnvall H, Haeggström JZ; ''Leukotriene A4 hydrolase in the human B-lymphocytic cell line Raji: indications of catalytically divergent forms of the enzyme.''; Arch Biochem Biophys, 1991 PubMed Europe PMC Scholia
  13. Gupta N, Gresser MJ, Ford-Hutchinson AW; ''Kinetic mechanism of glutathione conjugation to leukotriene A4 by leukotriene C4 synthase.''; Biochim Biophys Acta, 1998 PubMed Europe PMC Scholia
  14. Rudberg PC, Tholander F, Andberg M, Thunnissen MM, Haeggström JZ; ''Leukotriene A4 hydrolase: identification of a common carboxylate recognition site for the epoxide hydrolase and aminopeptidase substrates.''; J Biol Chem, 2004 PubMed Europe PMC Scholia
  15. Rouzer CA, Matsumoto T, Samuelsson B; ''Single protein from human leukocytes possesses 5-lipoxygenase and leukotriene A4 synthase activities.''; Proc Natl Acad Sci U S A, 1986 PubMed Europe PMC Scholia
  16. Adachi H, Kubota I, Okamura N, Iwata H, Tsujimoto M, Nakazato H, Nishihara T, Noguchi T; ''Purification and characterization of human microsomal dipeptidase.''; J Biochem, 1989 PubMed Europe PMC Scholia
  17. Kalsotra A, Turman CM, Kikuta Y, Strobel HW; ''Expression and characterization of human cytochrome P450 4F11: Putative role in the metabolism of therapeutic drugs and eicosanoids.''; Toxicol Appl Pharmacol, 2004 PubMed Europe PMC Scholia
  18. Smyrniotis CJ, Barbour SR, Xia Z, Hixon MS, Holman TR; ''ATP allosterically activates the human 5-lipoxygenase molecular mechanism of arachidonic acid and 5(S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid.''; Biochemistry, 2014 PubMed Europe PMC Scholia
  19. Kikuta Y, Kusunose E, Sumimoto H, Mizukami Y, Takeshige K, Sakaki T, Yabusaki Y, Kusunose M; ''Purification and characterization of recombinant human neutrophil leukotriene B4 omega-hydroxylase (cytochrome P450 4F3).''; Arch Biochem Biophys, 1998 PubMed Europe PMC Scholia
  20. Horn T, Reddy Kakularam K, Anton M, Richter C, Reddanna P, Kuhn H; ''Functional characterization of genetic enzyme variations in human lipoxygenases.''; Redox Biol, 2013 PubMed Europe PMC Scholia
  21. Kikuta Y, Kusunose E, Kusunose M; ''Characterization of human liver leukotriene B(4) omega-hydroxylase P450 (CYP4F2).''; J Biochem, 2000 PubMed Europe PMC Scholia
  22. Berry KA, Borgeat P, Gosselin J, Flamand L, Murphy RC; ''Urinary metabolites of leukotriene B4 in the human subject.''; J Biol Chem, 2003 PubMed Europe PMC Scholia
  23. Raulf M, König W, Köller M, Stüning M; ''Release and functional characterization of the leukotriene D4-metabolizing enzyme (dipeptidase) from human polymorphonuclear leucocytes.''; Scand J Immunol, 1987 PubMed Europe PMC Scholia
  24. 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 PubMed Europe PMC Scholia
  25. McGee J, Fitzpatrick F; ''Enzymatic hydration of leukotriene A4. Purification and characterization of a novel epoxide hydrolase from human erythrocytes.''; J Biol Chem, 1985 PubMed Europe PMC Scholia
  26. Kikuta Y, Kato M, Yamashita Y, Miyauchi Y, Tanaka K, Kamada N, Kusunose M; ''Human leukotriene B4 omega-hydroxylase (CYP4F3) gene: molecular cloning and chromosomal localization.''; DNA Cell Biol, 1998 PubMed Europe PMC Scholia
  27. Stec DE, Roman RJ, Flasch A, Rieder MJ; ''Functional polymorphism in human CYP4F2 decreases 20-HETE production.''; Physiol Genomics, 2007 PubMed Europe PMC Scholia
  28. Dalli J, Vlasakov I, Riley IR, Rodriguez AR, Spur BW, Petasis NA, Chiang N, Serhan CN; ''Maresin conjugates in tissue regeneration biosynthesis enzymes in human macrophages.''; Proc Natl Acad Sci U S A, 2016 PubMed Europe PMC Scholia
  29. Sjölinder M, Tornhamre S, Claesson HE, Hydman J, Lindgren J; ''Characterization of a leukotriene C4 export mechanism in human platelets: possible involvement of multidrug resistance-associated protein 1.''; J Lipid Res, 1999 PubMed Europe PMC Scholia
  30. Dalli J, Zhu M, Vlasenko NA, Deng B, Haeggström JZ, Petasis NA, Serhan CN; ''The novel 13S,14S-epoxy-maresin is converted by human macrophages to maresin 1 (MaR1), inhibits leukotriene A4 hydrolase (LTA4H), and shifts macrophage phenotype.''; FASEB J, 2013 PubMed Europe PMC Scholia
  31. Murphy RC, Gijón MA; ''Biosynthesis and metabolism of leukotrienes.''; Biochem J, 2007 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
125324
Approved
RARE
view22:15, 31 January 2023LarsgwFix references
122629view10:53, 22 April 2022FehrhartUpdated layout for pathways
122590view10:21, 20 April 2022EweitzModified title
122520
IEM
view12:55, 13 April 2022DeSlUpdated chapter nr in description
122499view08:17, 13 April 2022DeSlOntology Term : 'brain ischemia' added !
122498view08:16, 13 April 2022DeSlOntology Term : 'cerebrovascular disease' added !
122497view08:13, 13 April 2022DeSlAdded more details to description
122496view07:55, 13 April 2022DeSlUpdated description of PW
122495view07:50, 13 April 2022DeSlUpdated info for DPEP1 disorder; added link to other relevant PW
122494view07:42, 13 April 2022DeSlOntology Term : 'gamma-glutamyl transpeptidase deficiency' added !
122257view13:36, 16 March 2022PeterSwanenbergadded references
122173view21:26, 14 March 2022PeterSwanenbergOntology Term : 'cerebral infarction' added !
122172view21:24, 14 March 2022PeterSwanenbergOntology Term : 'autosomal dominant nonsyndromic deafness' added !
122171view21:18, 14 March 2022PeterSwanenbergtried making the RHEA and reactome IDs functional

some small layout changes

added 2 new diseases
122098view22:39, 10 March 2022DeSlConnected unconnected line
122097view22:27, 10 March 2022DeSlAdded comments on 16-carboxy-LTB4
122096view22:08, 10 March 2022DeSlAdded some more IDs for metabolites
122090view16:34, 10 March 2022DeSlAdded LTE3 metabolite node (no ID found yet)
122089view16:23, 10 March 2022DeSlAdded additonal ref for not annotated metabolites bottom right corner, added two protein annotations
122000view08:34, 9 March 2022PeterSwanenbergOntology Term : 'glutathionuria disease pathway' added !
121999view08:33, 9 March 2022PeterSwanenbergOntology Term : 'leukotriene C4 synthase deficiency pathway' added !
121650view11:17, 23 February 2022PeterSwanenbergLayout changes
121647view11:07, 23 February 2022PeterSwanenbergLayout changes
121642view10:05, 23 February 2022PeterSwanenbergAdded literature and some layout changes
121635view16:24, 22 February 2022PeterSwanenbergChanged one identifier
121599view18:10, 21 February 2022AndraOntology Term : 'leukotriene metabolic pathway' added !
121544view10:13, 21 February 2022PeterSwanenbergModified description
121540view10:10, 21 February 2022PeterSwanenbergAdded Legend
121534view09:07, 21 February 2022PeterSwanenbergForgot an arrow
121533view09:06, 21 February 2022PeterSwanenbergChange layout and addes some Pahtway nodes
121374view19:30, 16 February 2022PeterSwanenbergAdded enzymes and changed the layout
121344view18:15, 15 February 2022PeterSwanenbergCorrected the Rhea pathways

added extra found enzymes

applied OMIM numbers to disease
121188view22:06, 10 February 2022PeterSwanenbergAdded rhea pathways
121129view14:06, 9 February 2022PeterSwanenberg
121120view10:13, 9 February 2022PeterSwanenberg
121119view10:00, 9 February 2022PeterSwanenbergNew pathway

External references

DataNodes

View all...
Name  ↓Type  ↓Database reference  ↓Comment  ↓
(C2)-COOH-LTBMetabolite
(C2)-COOH-LTEMetabolite
12-Oxo-LTB4MetaboliteCHEBI:27814 (ChEBI) Found in reactome reaction: arachidonic acid metabolism
16-carboxy-LTB4Metabolite
16-carboxy-LTE4Metabolite
18-COOH-LTB4MetaboliteCHEBI:63980 (ChEBI)
  • Found in reactome reaction: arachidonic acid metabolism
  • Full name: 18-hydroxy-18-oxo-dinorleukotriene B4
18-carboxy-LTE4Metabolite
20-COOH-LTB4MetaboliteCHEBI:27562 (ChEBI)
  • CHEBI id lead to20-hydroxy-20-oxoleukotriene but according to Rhea is the same as 20-carboxy-LTB4
  • have both CHEBI: 27562 and 90722 who are very similair
20-carboxy-LTE4MetaboliteCHEBI:134517 (ChEBI)
20-hydroxy-LTB4MetaboliteCHEBI:15646 (ChEBI)
20-hydroxy-LTE4MetaboliteCHEBI:28700 (ChEBI)
20-oxo-LTB4MetaboliteCHEBI:63979 (ChEBI)
  • looks firs like a conversion from hydroxy to oxo (RHEA:48668) and then from oxo to carboxy (RHEA:48672)
  • found by RHE reactions described above
5-HPETEMetaboliteCHEBI:15632 (ChEBI) 5-HPETE: 5-Hydroperoxyeicosatetraenoic acid
5-LOAPGeneProductENSG00000132965 (Ensembl) 5-LOAP: 5-lipoxygenase-activating protein found as ALOX5AP
5-LOGeneProductENSG00000012779 (Ensembl)
  • 5-LO: 5-lipoxygenase
  • Found as gene ALOX5
ABCC1???GeneProductENSG00000103222 (Ensembl)
  • Found in reactome reaction: arachidonic acid metabolism
  • do i need to show that LTC4 is tranpsorted to the extracellular region
Arachidonic acidMetaboliteCHEBI:15843 (ChEBI)
CYP4F3GeneProductENSG00000186529 (Ensembl) CYP4F3 or LTB4H
DPEP1?GeneProductENSG00000015413 (Ensembl)
  • DPEP1: membrane-bound dipeptidase
DPEP2GeneProductENSG00000167261 (Ensembl)
  • Full name: Dipeptidase 1
  • Found in RHEA reaction with uniprot
GGT1GeneProductENSG00000100031 (Ensembl) GGT1: Gamma-glutamyl transpeptidase
GGT5GeneProductENSG00000099998 (Ensembl)
  • GGT5 or GGTLA1
  • Founde by rhea reaction and than the uniprot search
GlutathioneMetaboliteCHEBI:16856 (ChEBI)
LTA4MetaboliteCHEBI:15651 (ChEBI)
LTA4HGeneProductENSG00000111144 (Ensembl)
LTB4MetaboliteCHEBI:15647 (ChEBI)
LTC4MetaboliteCHEBI:16978 (ChEBI)
LTC4SGeneProductENSG00000213316 (Ensembl) LTC4S: LTC4 synthase
LTD4MetaboliteCHEBI:28666 (ChEBI)
LTE4MetaboliteCHEBI:15650 (ChEBI)
N-acetyl-LTE4MetaboliteCHEBI:7210 (ChEBI)
Other reactome pathways needed?Metabolite
PTGR1GeneProductENSG00000106853 (Ensembl) Found in reactome reaction: arachidonic acid metabolism
leukotriene-E4 20-monooxygenaseGeneProductBRENDA:EC1.14.13.34 (BRENDA)
  • Found on Rhea in the cross-references section in MetaCyc that leukotriene-E4 20-monooxygenase is involved in this reaction

    https://biocyc.org/META/NEW-IMAGE?type=REACTION&object=LEUKOTRIENE-E4-20-MONOOXYGENASE-RXN

  • BRENDA site: https://www.brenda-enzymes.org/enzyme.php?ecno=1.14.13.34#SYSTEMATIC%20NAME

Annotated Interactions

View all...
Source  ↓Target  ↓Type  ↓Database reference  ↓Comment  ↓
20-COOH-LTB418-COOH-LTB4mim-conversionId: R-HSA-2161790.2 (Reactome)
20-hydroxy-LTB420-oxo-LTB4mim-conversionRHEA:48669 (Rhea)
20-oxo-LTB420-COOH-LTB4mim-conversionRHEA:48673 (Rhea) looks firs like a conversion from hydroxy to oxo (RHEA:48668) and then from oxo to carboxy (RHEA:48672)
5-HPETELTA4mim-conversionRHEA:17962 (Rhea)
Arachidonic acid5-HPETEmim-conversionRHEA:17486 (Rhea)
LTA4LTB4mim-conversionRHEA:22325 (Rhea)
LTA4LTC4mim-conversionRHEA:17619 (Rhea)
LTB412-Oxo-LTB4mim-conversionRHEA:50609 (Rhea) Found in reactome reaction: arachidonic acid metabolism
LTB420-hydroxy-LTB4mim-conversionRHEA:22177 (Rhea)
LTC4LTC4ArrowId: R-HSA-266070.1 (Reactome)
LTC4LTD4mim-conversionRHEA:31564 (Rhea)
LTD4LTE4mim-conversionRHEA:48616 (Rhea)
  • DPEP1 is in the undefined reaction direction not from left-to-right
  • Reactome Id does say conversion to LTE4 ID:R-HSA-266012.3
LTD4LTE4mim-conversionRHEA:48617 (Rhea) DPEP1 is in the undefined reaction direction in RHEA:48616, but not from left-to-right
LTE420-hydroxy-LTE4mim-conversionRHEA:24121 (Rhea)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5171"
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