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FUNCTION Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced lipoxygenases activity (PubMed:12881489, PubMed:17045234, PubMed:20921226, PubMed:20923767). The hydroperoxide isomerase activity catalyzes the isomerization of hydroperoxides, derived from arachidonic and linoleic acid by ALOX12B, into hepoxilin-type epoxyalcohols and ketones (PubMed:12881489, PubMed:17045234, PubMed:20923767). In presence of oxygen, oxygenates polyunsaturated fatty acids, including arachidonic acid, to produce fatty acid hydroperoxides (PubMed:20921226). In the skin, acts downstream of ALOX12B on the linoleate moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins (PubMed:21558561). Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss (PubMed:21558561). In parallel, it may have a signaling function in barrier formation through the production of hepoxilins metabolites (PubMed:21558561). Also plays a role in adipocyte differentiation through hepoxilin A3 and hepoxilin B3 production which in turn activate PPARG (By similarity). Through the production of hepoxilins in the spinal cord, it may regulate inflammatory tactile allodynia (By similarity).CATALYTIC ACTIVITY a hydroperoxyeicosatetraenoate = a hydroxy-epoxy-eicosatetraenoateCATALYTIC ACTIVITY (12R)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = (8R)-hydroxy-(11R,12R)-epoxy-(5Z,9E,14Z)-eicosatrienoateCATALYTIC ACTIVITY (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = (8R)-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoateCATALYTIC ACTIVITY (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = (10R)-hydroxy-(11S,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoateCATALYTIC ACTIVITY (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = (13R)-hydroxy-(14S,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoateCATALYTIC ACTIVITY (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = 7R-hydroxy-5S,6S-epoxy-(8Z,11Z,14Z)-eicosatrienoateCATALYTIC ACTIVITY (13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 11-hydroxy-(12S,13S)-epoxy-(9Z)-octadecenoateCATALYTIC ACTIVITY N-[omega-(9R)-hydroperoxy-(10E,12Z)-octadecadienoyloxy]acyl-beta-D-glucosyl-(1<->1)-octadecasphing-4E-enine = a N-[omega-(9R,10R)-epoxy-(13R)-hydroxy-(11E)-octadecenoyloxy]acyl-beta-D-glucosyl-(1<->1)-sphing-4E-enineCATALYTIC ACTIVITY a N-[omega-(9R)-hydroperoxy-(10E,12Z)-octadecadienoyloxy]-acylsphin-4E-enine = a N-[omega-(9R,10R)-epoxy-(13R)-hydroxy-(11E)-octadecenoyloxy]-acylsphing-4E-enineCATALYTIC ACTIVITY a hydroperoxyeicosatetraenoate = an oxoeicosatetraenoate + H2OCATALYTIC ACTIVITY (12R)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = 12-oxo-(5Z,8Z,10E,14Z)-eicosatetraenoate + H2OCATALYTIC ACTIVITY (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = 12-oxo-(5Z,8Z,10E,14Z)-eicosatetraenoate + H2OCATALYTIC ACTIVITY (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2OCATALYTIC ACTIVITY (13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 13-oxo-(9Z,11E)-octadecadienoate + H2OCATALYTIC ACTIVITY (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate = (10R)-hydroxy-(8S,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoateCATALYTIC ACTIVITY (8R)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate = 8-oxo-(5Z,9E,11Z,14Z)-eicosatetraenoate + H2OCATALYTIC ACTIVITY (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate = 8-oxo-(5Z,9E,11Z,14Z)-eicosatetraenoate + H2OCOFACTOR Binds 1 Fe cation per subunit.ACTIVITY REGULATION Lipoxygenase activity is activated by 13(S)-HPODE leading to an active free ferric enzyme (PubMed:20921226). The lipoxygenase and hydroperoxide isomerase activities are in competition and are reciprocally regulated by oxygen (PubMed:20923767). The oxygen reacts with an epoxyallylic radical intermediate leading to an epoxyallylic peroxyl radical, which, due to its limited reactivity within the enzyme active site, it dissociates and leaves the enzyme in the activated free ferric state (PubMed:20923767).BIOPHYSICOCHEMICAL PROPERTIES Has a 5 to 10 fold higher activity toward (12R)-HPETE (hydroperoxyeicosatetraenoic acid) compared to (12S)-HPETE and (15S)-HPETE (PubMed:12881489). From (12R)-HPETE produces a stereoisomer of hepoxilin A3 (PubMed:12881489). More active on hydroperoxides with an R configuration than an S one (PubMed:17045234).PATHWAY Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis.PATHWAY Lipid metabolism; sphingolipid metabolism.INTERACTION Predominantly expressed in skin.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the lipoxygenase family.ONLINE INFORMATION about water - Issue 153 of September 2013
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