BioPAX pathway converted from "LTA4 is hydolysed to LTB4 by LTA4H" in the Reactome database. LEFT-TO-RIGHT 3.3.2.6 LTA4 is hydrolyzed to LTB4 LTA4 is hydolysed to LTB4 by LTA4H Leukotriene A4 hydrolase (LTA4H) is a monomeric, soluble enzyme that catalyzes the hydrolysis of the allylic epoxide leukotriene A4 (LTA4) to the dihydroxy acid leukotriene B4 (LTB4) (Radmark et al. 1984, McGee & Fitzpatrick 1985). Authored: Jassal, Bijay, 2008-10-01 Reviewed: Rush, MG, 2012-11-10 Edited: Jassal, B, 2008-04-21 14:30:22 H2O water Reactome DB_ID: 29356 cytosol GENE ONTOLOGY GO:0005829 water [ChEBI:15377] water ChEBI CHEBI:15377 Reactome Database ID Release 82 29356 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29356 Reactome R-ALL-29356 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29356.5 Reactome http://www.reactome.org COMPOUND C00001 additional information MI MI:0361 LTA4 leukotriene A4 Reactome DB_ID: 265281 leukotriene A4 [ChEBI:15651] leukotriene A4 ChEBI CHEBI:15651 Reactome Database ID Release 82 265281 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=265281 Reactome R-ALL-265281 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-265281.3 COMPOUND C00909 LTB4 Leukotriene-B(4) omega-hydroxylase leukotriene B4 Leukotriene-B(4) 20-monooxygenase Reactome DB_ID: 266056 leukotriene B4 [ChEBI:15647] leukotriene B4 ChEBI CHEBI:15647 Reactome Database ID Release 82 266056 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=266056 Reactome R-ALL-266056 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-266056.3 COMPOUND C02165 ACTIVATION LTA4H:Zn2+ LTA4 hydrolase (Zinc cofactor) Reactome DB_ID: 266038 LTA4H Leukotriene A-4 hydrolase-1 LKHA4_HUMAN Reactome DB_ID: 266022 UniProt:P09960 LTA4H LTA4H LTA4 FUNCTION Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities. Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the pro-inflammatory mediator leukotriene B4 (LTB4) (PubMed:11917124, PubMed:12207002, PubMed:15078870, PubMed:18804029, PubMed:1897988, PubMed:1975494, PubMed:2244921). Has also aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides (PubMed:20813919, PubMed:18804029). In addition to its pro-inflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL) (PubMed:20813919, PubMed:24591641). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions (PubMed:21206090).ACTIVITY REGULATION Inhibited by bestatin (PubMed:11175901). The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379 (PubMed:7667299). 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity (PubMed:24591641).PATHWAY Lipid metabolism; leukotriene B4 biosynthesis.SUBUNIT Monomer.TISSUE SPECIFICITY Isoform 1 and isoform 2 are expressed in monocytes, lymphocytes, neutrophils, reticulocytes, platelets and fibroblasts.PTM Phosphorylation at Ser-416 inhibits leukotriene-A4 hydrolase activity.SIMILARITY Belongs to the peptidase M1 family. Homo sapiens NCBI Taxonomy 9606 UniProt P09960 2 EQUAL 611 EQUAL Reactome Database ID Release 82 266022 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=266022 Reactome R-HSA-266022 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-266022.1 1 Zn2+ Zn++ zinc(2+) Zinc ion Zn(II) Reactome DB_ID: 29426 zinc(2+) [ChEBI:29105] zinc(2+) ChEBI CHEBI:29105 Reactome Database ID Release 82 29426 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29426 Reactome R-ALL-29426 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29426.3 COMPOUND C00038 1 Reactome Database ID Release 82 266038 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=266038 Reactome R-HSA-266038 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-266038.1 GENE ONTOLOGY GO:0004463 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 82 266024 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=266024 Reactome Database ID Release 82 266072 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=266072 Reactome R-HSA-266072 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-266072.1 2995393 Pubmed 1985 Enzymatic hydration of leukotriene A4. Purification and characterization of a novel epoxide hydrolase from human erythrocytes McGee, J Fitzpatrick, F J Biol Chem 260:12832-7 6490615 Pubmed 1984 Leukotriene A4 hydrolase in human leukocytes. Purification and properties Rådmark, O Shimizu, T Jörnvall, H Samuelsson, B J Biol Chem 259:12339-45