BioPAX pathway converted from "ALOX5 dehydrogenates 4(S)-Hp-17(S)-HDHA to 4S(5)-epoxy-17(S)-HDHA" in the Reactome database.1.13.11.34ALOX5 dehydrogenates 4(S)-Hp-17(S)-HDHA to 4S(5)-epoxy-17(S)-HDHAALOX5 dehydrogenates 4(S)-Hp-17(S)-HDHA to 4S(5)-epoxy-17(S)-HDHA5-lipoxygenase (ALOX5) possesses dual lipoxygenase activity (Shimizu et al. 1984). In polymorphonuclear (PMN) cells, ALOX5 can epoxygenate (via dehydration) 4(S)-hydroperoxy-17(S)-hydroxydocosahexaenoic acid (4(S)-Hp-17(S)-HDHA) to form 4S(5)-epoxy-17(S)-hydroxydocosahexaenoic acid (4S(5)-epoxy-17(S)-HDHA (Serhan et al. 2002).Authored: Jassal, Bijay, 2017-09-05Reviewed: Hansen, Trond Vidar, 2018-02-21Edited: Jassal, Bijay, 2017-09-05Reactome DB_ID: 293661cytosolGO0005829NADP(+) [ChEBI:18009]NADP(+)Reactomehttp://www.reactome.orgChEBI18009Reactome DB_ID: 902479714(S)-hydroperoxy-17(S)-hydroxydocosahexaenoic acid [ChEBI:138641]4(S)-hydroperoxy-17(S)-hydroxydocosahexaenoic acidChEBI138641Reactome DB_ID: 293641NADPH [ChEBI:16474]NADPHTPNHChEBI16474Reactome DB_ID: 902478114S(5)-epoxy-17(S)-hydroxydocosahexaenoic acid [ChEBI:138647]4S(5)-epoxy-17(S)-hydroxydocosahexaenoic acidChEBI138647PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 429010UniProt:P09917 ALOX5ALOX5LOG5ALOX5FUNCTION Catalyzes the oxygenation of arachidonic acid to 5-hydroperoxyicosatetraenoic acid (5-HPETE) followed by the dehydration of the hydroperoxide into an epoxide, 5,6- oxidoicosatetraenoic acid (LTA4), thereby participates in the first step in leukotriene biosynthesis and in the inflammatory processes (PubMed:8631361, PubMed:21233389, PubMed:22516296, PubMed:24282679, PubMed:19022417, PubMed:23246375, PubMed:8615788, PubMed:24893149, PubMed:31664810). Also catalyzes the oxygenation of arachidonic acid into 8-hydroperoxyicosatetraenoic acid (8-HPETE) and 12-hydroperoxyicosatetraenoic acid (12-HPETE) (PubMed:23246375). Although arachidonic acid is the preferred substrate, can also metabolize oxidized fatty acids derived from arachidonic acid such as (15S)-HETE, eicosapentaenoic acid (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoic (DHA) acid which leads to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore plays a role in anti-inflammatory response (PubMed:21206090, PubMed:31664810, PubMed:8615788, PubMed:17114001). Also displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Oxidation of docosahexaenoic acid directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). Does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxins isomers (PubMed:31664810). In addition to inflammatory processes, participates in dendritic cell migration, wound healing through an antioxidant mechanism based on HO1 regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, establishes an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). Also may play a role in glucose homeostasis, regulation of INS secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity).ACTIVITY REGULATION Undergoes a sequential loss of the oxygenase and pseudoperoxidase activities which is dependent on the structural characteristics of the substrate for the reaction, on oxygen concentration and on exposure to phospholipids and calcium (PubMed:8631361). 15-HETE and other 15-mono-hydroxyeicosanoids exhibit the highest inhibitory potencies in their capability of suppressing 5-lipoxygenation of arachidonic acid, whereas the other HETEs, (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoic acid (5,15-diHETE) as well as octadecanoids, are modest or poor inhibitors (PubMed:8615788). The formation of (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate is strongly stimulated by either hydroperoxypolyenoic fatty acids or arachidonic acid (PubMed:8615788). Arachidonate 5-lipoxygenase and leukotriene A4 synthase activities are allosterically increased by ATP (PubMed:24893149).PATHWAY Lipid metabolism; leukotriene A4 biosynthesis.SUBUNIT Homodimer (PubMed:22516296, PubMed:21233389). Interacts with ALOX5AP and LTC4S (PubMed:19233132). Interacts with COTL1, the interaction is required for stability and efficient catalytic activity (PubMed:19807693). Interacts with PIK3R1; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS) (PubMed:21200133). Interacts (via PLAT domain) with DICER1 (via Dicer dsRNA-binding fold domain); this interaction enhances arachidonate 5-lipoxygenase activity and modifies the miRNA precursor processing activity of DICER1 (PubMed:19022417).PTM Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid (PubMed:11844797, PubMed:18978352). Phosphorylation on Ser-524 by PKA has an inhibitory effect (PubMed:15280375). Phosphorylation on Ser-272 prevents export from the nucleus (PubMed:11844797, PubMed:18978352). Phosphorylation at Ser-524 is stimulated by 8-bromo-3',5'-cyclic AMP or prostaglandin E2 (PubMed:26210919).SIMILARITY Belongs to the lipoxygenase family.Homo sapiensNCBI Taxonomy9606UniProtP09917Chain Coordinates2EQUAL674EQUALGO0004051GO molecular functionReactome Database ID Release 759020578Database 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=9020578Reactome Database ID Release 759020277Database 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=9020277ReactomeR-HSA-90202771Reactome 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-9020277.16322165Pubmed1984Enzyme with dual lipoxygenase activities catalyzes leukotriene A4 synthesis from arachidonic acidShimizu, TRådmark, OSamuelsson, BProc. Natl. Acad. Sci. U.S.A. 81:689-9312391014Pubmed2002Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signalsSerhan, Charles NHong, SongGronert, KarstenColgan, Sean PDevchand, Pallavi RMirick, GudrunMoussignac, Rose-LaureJ. Exp. Med. 196:1025-37