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Information on EC 1.13.11.33 - arachidonate 15-lipoxygenase and Organism(s) Rattus norvegicus and UniProt Accession Q8K4F2
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1.13.11.33 arachidonate 15-lipoxygenaseIUBMB Comments
The product is rapidly reduced to the corresponding 15S-hydroxy compound.
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Word Map
- 1.13.11.33
- lipoxygenases
- cox-2
- 15-hete
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polyunsaturated
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leukotriene
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eicosanoids
- hydroperoxide
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12-lipoxygenase
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cyclooxygenases
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lipoxins
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15s-hydroxyeicosatetraenoic
- ndga
- alox15b
- 12/15-lipoxygenase
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nordihydroguaiaretic
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pro-resolving
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lipoxygenation
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resolvins
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hodes
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13-hydroxyoctadecadienoic
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lipid-peroxidating
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leukocyte-type
- oxylipins
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platelet-type
- medicine
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protectins
- drug development
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
Synonyms
15-lox, 15-lo-1, 15-lox-2, 15-lox2, arachidonate 15-lipoxygenase, soybean 15-lipoxygenase, 15-lipoxygenase-2, 15lo1, 15-hlo, 15-lipoxygenase 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
15-lipoxygenase
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15-LOX
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arachidonic acid 15-lipoxygenase
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linoleic acid omega-6-lipoxygenase
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omega-6 lipoxygenase
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oxygenase, arachidonate 15-lip-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate
the reaction proceeds via hydrogen abstraction, peroxide cleavage, radical rearrangement, and epoxide formation. To initiate the reaction the ferrous LOX is first activated by peroxide-dependent oxidation to a ferric form. The lipohydroperoxidase activity is initiatedwhen a lipid hydroperoxide (ROOH) is bound at the active site of the enzyme. The enzyme then catalyzes a homolytic cleavage of the hydroperoxy bond, which leads to the formation of an oxygen-centered alkoxy radical, a hydroxyl and oxidizes the ferrous iron to a ferric form. Then the enzyme binds a linoleic acid molecule (or an alterative reductant such as guaiacol) and releases a carbon-centered linoleic radical. This reaction reduces the ferric LOX back to its ferrous form to start the next catalytic cycle. The released radical intermediates may then initiate free radical secondary reactions leading to the formation of mixed oxygenated and non-oxygenated linoleic acid dimer
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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oxidation
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reduction
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dioxygenation
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PATHWAY SOURCE
PATHWAYS
BRENDA
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-, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
arachidonate:oxygen 15-oxidoreductase
The product is rapidly reduced to the corresponding 15S-hydroxy compound.
CAS REGISTRY NUMBER
COMMENTARY
82249-77-2
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arachidonate + O2
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyeicosa-5,8,11,13-tetraenoate
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?
arachidonate + O2
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate
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?
arachidonate + O2
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyeicosa-5,8,11,13-tetraenoate
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?
arachidonate + O2
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyeicosa-5,8,11,13-tetraenoate
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the enzyme is regulated pretranslational, translational and posttranslational
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?
arachidonate + O2
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyeicosa-5,8,11,13-tetraenoate
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induction of experimental anemia leads to a systemic up-regulation of 12/15-lipoxygenases expression
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?
additional information
?
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trans-10,cis-12-conjugated linoleic acid is not a substrate for 15-LOX-1
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?
additional information
?
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in the brain, the principal 12/15-LOX metabolites of arachidonate are (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate, cf. EC 1.13.11.31, and (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate
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?
additional information
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the major reaction products are identified as(8S,15S,5Z,9E,11Z,13E)-8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8S,15S-DiHpETE) and (5S,15S,6E,8Z,11Z,13E)-5,15-dihydroperoxy-6,8,11,13-eicosatetraenoic acid (5S,15S-DiHPETE) and the stereochemistry of the reaction is compatible with an inverse substrate orientation
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?
additional information
?
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enzyme substrate specificity, overview. The ALOX15 enzyme activity is not restricted to free polyenoic fatty acids since phospholipids and even biomembranes and lipoproteins are suitable ALOX15 substrates. The ALOX15 orthologue is capable of converting hydroperoxy fatty acids to epoxy leukotrienes. Product specificity with polyenoic acids and with complex substrates, and alteration of product specificity by substrate modification. Intraenzyme oxygen movement
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arachidonate + O2
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate
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?
arachidonate + O2
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyeicosa-5,8,11,13-tetraenoate
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the enzyme is regulated pretranslational, translational and posttranslational
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?
arachidonate + O2
(5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyeicosa-5,8,11,13-tetraenoate
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induction of experimental anemia leads to a systemic up-regulation of 12/15-lipoxygenases expression
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?
additional information
?
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in the brain, the principal 12/15-LOX metabolites of arachidonate are (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate, cf. EC 1.13.11.31, and (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate
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?
additional information
?
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the major reaction products are identified as(8S,15S,5Z,9E,11Z,13E)-8,15-dihydroperoxy-5,9,11,13-eicosatetraenoic acid (8S,15S-DiHpETE) and (5S,15S,6E,8Z,11Z,13E)-5,15-dihydroperoxy-6,8,11,13-eicosatetraenoic acid (5S,15S-DiHPETE) and the stereochemistry of the reaction is compatible with an inverse substrate orientation
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
certain oxazole-4-carbonitrile based LOX inhibitors share a high inhibitory potency for human and mouse ALOX15 but hardly inhibit other mammalian LOX-isoforms
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
ALOX15 is usually present as catalytically silent ferrous enzyme. To initiate fatty acid oxygenation, the enzyme must first be oxidized to a ferric form capable of initiating hydrogen abstraction. Unfortunately, single activation of the enzyme is not sufficient to keep it running, since during catalysis small quantities of radical intermediates might escape from the active site leaving the enzyme in an inactive ferrous (Fe2+) form. To keep the reaction at quasistationary levels, repeated enzyme activation is required and the primary oxygenation products appear to serve as enzyme activators. In this sense, the LOX exhibits autocatalytic properties
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
increased expression of 12/15-LOX, predominantly in neurons, and elevated production of 12(S)-hydroperoxyicosatetraenoate and 15(S)-hydroperoxyicosatetraenoate in ischemic brain
primary cortical neurons, increased expression of 12/15-LOX, predominantly in neurons, and elevated production of 12(S)-hydroperoxyicosatetraenoate and 15(S)-hydroperoxyicosatetraenoate in ischemic brain
additional information
tissue specific expression of ALOX15 and transcriptional expression regulation, overview
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
12/15-lipoxygenase metabolites of arachidonic acid activate PPARgamma, involvement of 12(S)- and 15(S)-hydroperoxyicosatetraenoate in the regulation of PPARgamma following cerebral ischemia and effects on ischemia-induced inflammatory response. 12(S)-HETE and 15(S)-HETE elicit neuroprotection in rats exposed to focal ischemia. PPARgamma is a member of the nuclear hormone receptorfamily of ligand-dependent transcription factors. PPARgamma regulates genes that are implicated in adipocyte differentiation, lipid and glucose metabolism, and insulin sensitivity
physiological function
lipoxygenases (LOX) form a family of lipid peroxidizing enzymes, which are implicated in a number of physiological processes and in the pathogenesis of inflammatory, hyperproliferative and neurodegenerative diseases. Physiological roles of ALOX15, detailed overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). LX15B_RAT
677
0
76145
Swiss-Prot
other Location (Reliability: 4)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
mammalian ALOX15 enzyme structure comparisons, overview
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kuehn, H.; Heydeck, D.; Brinckman, R.; Trebus, F.
Regulation of cellular 15-lipoxygenase activity on pretranslational, translational, and posttranslational levels
Lipids
34
S273-S279
1999
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus
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Reinhold, S.W.; Vitzthum, H.; Filbeck, T.; Wolf, K.; Lattas, C.; Riegger, G.A.; Kurtz, A.; Kraemer, B.K.
Gene expression of 5-, 12-, and 15-lipoxygenases and leukotriene receptors along the rat nephron
Am. J. Physiol. Renal Physiol.
290
F864-F872
2006
Rattus norvegicus (Q8K4F2)
Cho, H.; Gallaher, D.D.; Csallany, A.S.
Conjugated linoleic acid, cis-9,trans-11, is a substrate for pulmonary 15-lipoxygenase-1 in rat
J. Agric. Food Chem.
53
7262-7266
2005
Rattus norvegicus
Bhattacharya, S.; Mathew, G.; Jayne, D.G.; Pelengaris, S.; Khan, M.
15-lipoxygenase-1 in colorectal cancer: a review
Tumour Biol.
30
185-199
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Ivanov, I.; Kuhn, H.; Heydeck, D.
Structural and functional biology of arachidonic acid 15-lipoxygenase-1 (ALOX15)
Gene
573
1-32
2015
Oryctolagus cuniculus (P12530), Oryctolagus cuniculus, Homo sapiens (P16050), Homo sapiens, Mus musculus (P39654), Mus musculus, Rattus norvegicus (Q02759)
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