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MetaCyc Pathway: leukotriene biosynthesis
Traceable author statement to experimental supportInferred by computational analysisAuthor statement

Pathway diagram: leukotriene biosynthesis

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisHormones Biosynthesis

Some taxa known to possess this pathway include : Homo sapiens

Expected Taxonomic Range: Vertebrata

Leukotrienes are proinflammatory metabolites of arachidonic acid that activate and amplify innate and adaptive immune responses. They also have roles in pathologic immune responses, mediating contraction of bronchial smooth muscles and chemoattraction of lymphocytes. The enzymes in this pathway are therefore targets for therapeutic intervention in allergic responses [RinaldoMatthis10]. Leukotriene B4 (LTB4) is a very potent chemoattractant, while LTC4 stimulates bronchial constriction in asthmatics. Enzymes in this biosynthetic pathway are also targets for cardiovascular therapies. Additional regulatory proteins are also candidate drug targets, such as the 5-lipoxygenase activating protein (FLAP), which has been linked to increased risk for myocardial infarction and stroke [Helgadottir04].

Unification Links: Reactome:15354

Created 24-Jun-2010 by Trupp M, SRI International


Helgadottir04: Helgadottir A, Manolescu A, Thorleifsson G, Gretarsdottir S, Jonsdottir H, Thorsteinsdottir U, Samani NJ, Gudmundsson G, Grant SF, Thorgeirsson G, Sveinbjornsdottir S, Valdimarsson EM, Matthiasson SE, Johannsson H, Gudmundsdottir O, Gurney ME, Sainz J, Thorhallsdottir M, Andresdottir M, Frigge ML, Topol EJ, Kong A, Gudnason V, Hakonarson H, Gulcher JR, Stefansson K (2004). "The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke." Nat Genet 36(3);233-9. PMID: 14770184

Murphy07: Murphy RC, Gijon MA (2007). "Biosynthesis and metabolism of leukotrienes." Biochem J 405(3);379-95. PMID: 17623009

RinaldoMatthis10: Rinaldo-Matthis A, Haeggstrom JZ (2010). "Structures and mechanisms of enzymes in the leukotriene cascade." Biochimie 92(6);676-81. PMID: 20097252

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Adachi89: Adachi H, Kubota I, Okamura N, Iwata H, Tsujimoto M, Nakazato H, Nishihara T, Noguchi T (1989). "Purification and characterization of human microsomal dipeptidase." J Biochem 105(6);957-61. PMID: 2768222

Adachi90: Adachi H, Tawaragi Y, Inuzuka C, Kubota I, Tsujimoto M, Nishihara T, Nakazato H (1990). "Primary structure of human microsomal dipeptidase deduced from molecular cloning." J Biol Chem 265(7);3992-5. PMID: 2303490

Adachi93: Adachi H, Katayama T, Nakazato H, Tsujimoto M (1993). "Importance of Glu-125 in the catalytic activity of human renal dipeptidase." Biochim Biophys Acta 1163(1);42-8. PMID: 8097406

Ahamed02: Ahamed J, Ali H (2002). "Distinct roles of receptor phosphorylation, G protein usage, and mitogen-activated protein kinase activation on platelet activating factor-induced leukotriene C(4) generation and chemokine production." J Biol Chem 277(25);22685-91. PMID: 11934880

Anderson82: Anderson ME, Allison RD, Meister A (1982). "Interconversion of leukotrienes catalyzed by purified gamma-glutamyl transpeptidase: concomitant formation of leukotriene D4 and gamma-glutamyl amino acids." Proc Natl Acad Sci U S A 79(4);1088-91. PMID: 6122208

Austruy93: Austruy E, Jeanpierre C, Antignac C, Whitmore SA, Van Cong N, Bernheim A, Callen DF, Junien C (1993). "Physical and genetic mapping of the dipeptidase gene DPEP1 to 16q24.3." Genomics 15(3);684-7. PMID: 7682195

Bigby00: Bigby TD (2000). "The leukotriene C(4) synthase gene and asthma." Am J Respir Cell Mol Biol 23(3);273-6. PMID: 10970815

Funk87: Funk CD, Radmark O, Fu JY, Matsumoto T, Jornvall H, Shimizu T, Samuelsson B (1987). "Molecular cloning and amino acid sequence of leukotriene A4 hydrolase." Proc Natl Acad Sci U S A 84(19);6677-81. PMID: 2821541

Funk89: Funk CD, Hoshiko S, Matsumoto T, Rdmark O, Samuelsson B (1989). "Characterization of the human 5-lipoxygenase gene." Proc Natl Acad Sci U S A 86(8);2587-91. PMID: 2565035

Habib03: Habib GM, Shi ZZ, Cuevas AA, Lieberman MW (2003). "Identification of two additional members of the membrane-bound dipeptidase family." FASEB J 17(10);1313-5. PMID: 12738806

Heisterkamp91: Heisterkamp N, Rajpert-De Meyts E, Uribe L, Forman HJ, Groffen J (1991). "Identification of a human gamma-glutamyl cleaving enzyme related to, but distinct from, gamma-glutamyl transpeptidase." Proc Natl Acad Sci U S A 88(14);6303-7. PMID: 1676842

Jakobsson00: Jakobsson PJ, Morgenstern R, Mancini J, Ford-Hutchinson A, Persson B (2000). "Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG). A widespread protein superfamily." Am J Respir Crit Care Med 161(2 Pt 2);S20-4. PMID: 10673221

Jendraschak96: Jendraschak E, Kaminski WE, Kiefl R, von Schacky C (1996). "The human leukotriene A4 hydrolase gene is expressed in two alternatively spliced mRNA forms." Biochem J 314 ( Pt 3);733-7. PMID: 8615763

Kawagishi02: Kawagishi Y, Mita H, Taniguchi M, Maruyama M, Oosaki R, Higashi N, Kashii T, Kobayashi M, Akiyama K (2002). "Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma." J Allergy Clin Immunol 109(6);936-42. PMID: 12063521

Lam89: Lam BK, Owen WF, Austen KF, Soberman RJ (1989). "The identification of a distinct export step following the biosynthesis of leukotriene C4 by human eosinophils." J Biol Chem 264(22);12885-9. PMID: 2753893

Lam94a: Lam BK, Penrose JF, Freeman GJ, Austen KF (1994). "Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4." Proc Natl Acad Sci U S A 91(16);7663-7. PMID: 8052639

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lee83b: Lee CW, Lewis RA, Corey EJ, Austen KF (1983). "Conversion of leukotriene D4 to leukotriene E4 by a dipeptidase released from the specific granule of human polymorphonuclear leucocytes." Immunology 48(1);27-35. PMID: 6293969

Mancini95: Mancini JA, Evans JF (1995). "Cloning and characterization of the human leukotriene A4 hydrolase gene." Eur J Biochem 231(1);65-71. PMID: 7628486

Mandal08: Mandal AK, Jones PB, Bair AM, Christmas P, Miller D, Yamin TT, Wisniewski D, Menke J, Evans JF, Hyman BT, Bacskai B, Chen M, Lee DM, Nikolic B, Soberman RJ (2008). "The nuclear membrane organization of leukotriene synthesis." Proc Natl Acad Sci U S A 105(51);20434-9. PMID: 19075240

Showing only 20 references. To show more, press the button "Show all references".

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Mon May 2, 2016, biocyc14.