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Enzyme Nomenclature
Information on EC 1.13.11.31 - arachidonate 12-lipoxygenase
for references in articles please use BRENDA:EC1.13.11.31
Word Map on EC 1.13.11.31
- 1.13.11.31
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arachidonic
- inflammation
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cyclooxygenase
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eicosanoids
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12-hete
- macrophage
- prostaglandin
- vascular
- aa
- neutrophil
- artery
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linoleic
- atherosclerosis
- endothelial
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polyunsaturated
- indomethacin
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12-hydroxyeicosatetraenoic
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hetes
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lipoxins
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thromboxane
- reticulocyte
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nordihydroguaiaretic
- baicalein
- monocyte
- asthma
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hydroperoxide
- atherogenesis
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eicosapentaenoic
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polymorphonuclear
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docosahexaenoic
- ndga
- aspirin
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a23187-stimulated
- etya
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polyenoic
- drug development
- zileuton
- medicine
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hydroxyeicosatetraenoic
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1-14carachidonic
- erythroderma
- ichthyosis
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5-lipoxygenase-activating
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resolvins
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5,8,11,14-eicosatetraynoic
- phenidone
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ichthyosiform
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13-hode
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hydroperoxy
- esculetin
- lipoxygenase-1
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eicosatetraynoic
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
1.13.11.31
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RECOMMENDED NAME
GeneOntology No.
arachidonate 12-lipoxygenase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dehydration
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dioxygenation
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oxidation
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redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
arachidonate:oxygen 12-oxidoreductase
The product is rapidly reduced to the corresponding 12S-hydroxy compound.
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CAS REGISTRY NUMBER
COMMENTARY
82391-43-3
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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395400, 395411, 395415, 395420, 395426, 395432, 395435, 657508, 657993, 658673, 659680, 660365, 660410, 676096, 686330, 686569, 688509, 688751, 702324, 702629, 703699, 706032, 712802, 726846, 727634, 727878, 727969, 728093, 728826
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395421, 395426, 395432, 395434, 657746, 659461, 659765, 659822, 671667, 684350, 702435, 703078, 703805, 704901, 704947, 705256, 727878, 728826
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four 12-lipoxygenase: 1.platelet-type 12-lipoxygenase, 2. leukocyte-type lipoxygenase, 3. epidermal-type lipoxygenase, 4. 12(R)-lipoxygenase
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wild-type Sprague-Dawley rats and iron-deficient Belgrade rats, three isozymes: platelet, leukocyte, and epidermis isozyme, Alox15 is a leukocyte-type isozyme
UniProt
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
macrophages that lack 12/15LO have enhanced transporter expression, reduced ATP-binding cassette G1 phosphorylation, and increased cholesterol efflux
malfunction
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12-LOX-overexpressing PC-3 cells show an enhanced invasive ability which results from an increase in MMP9 expression and secretion
malfunction
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cells with RNAi silenced 12/15-LO and stimulated with PDGF show an impaired STAT3 phosphorylation compared to cells transfected with the scrambled control
malfunction
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the time to cessation of bleeding in 12-LOX-/- mice is significantly prolonged. Mice deficient in 12-LOX show a significant attenuation of alphaIIbeta3 activation for both agonists compared to wild-type mice
physiological function
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the 12/15-LO pathway participates in the regulation of monocyte chemoattractant protein-1 expression in mouse macrophages
physiological function
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the 12/15-LO pathway participates in the regulation of monocyte chemoattractant protein-1 expression in mouse macrophages
physiological function
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12/15LO activity in the vessel wall contributes to atherogenesis by impairing the macrophage ATP-binding cassette transporter G1 cholesterol efflux pathway. 12/15LO activity reduces high density lipoprotein-mediated cholesterol efflux, ATP-binding cassette transporter G1 cellular expression. 12/15LO activity does not affect ATP-binding cassette transporter G1 mRNA expression
physiological function
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p12-LOX plays an important role in tumor development, is required for tumor promotion of epidermal cells. The enzyme is involved in activation of NF-kappaB in the tumor necrosis factor-alpha-stimulated JB6 P+ cells
physiological function
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12/15-LOX is a critical mediator of the chronic type 1 inflammatory response. Evolution of the immune response to Toxoplasma gondii is accompanied by an increasing requirement for 12/15-LOX mediated signaling. Although 12/15-LOX deficient mice are resistant to acute Toxoplasma gondii infection, 80% of 12/15-LOX-deficient mice die during chronic toxoplasmosis, compared to no deaths in wild-type controls. The enhanced susceptibility of 12/15-LOX-deficient mice to chronic toxoplasmosis is associated with reduced production of IL-12 and gamma interferon (IFN-gamma) that is not evident during acute infection. Ex vivo IFN-gamma production by 12/15-LOX-deficient splenocytes can be rescued by the addition of recombinant IL-12. 12/15-LOX does not play a role in macrophage killing of Toxoplasma gondii in vitro
physiological function
12/15LO plays a key role in activating the mitogen-activated protein kinase pathway. 12/15LO regulates ATP-binding cassette G1 expression and function through p38- and c-Jun N-terminal kinase 2-dependent mechanisms
physiological function
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increased expression of 2/15-LOX causes heart failure. 2/15-LOX induces cardiac inflammation. Alox15 transgenic mice develop systolic dysfunction. Cardiac fibrosis increases in Alox15 transgenic mice with advancing age and is associated with the infiltration of macrophages. Cardiac expression of monocyte chemoattractant protein 1 is up-regulated in Alox15 transgenic mice compared with wild-type mice. Disruption of 12/15-LOX significantly reduces cardiac monocyte chemoattractant protein-1 expression and macrophage infiltration, thereby improving systolic dysfunction induced by chronic pressure overload
physiological function
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endogenous 12/15-LOX defines the resident peritoneal macrophage population and regulates both the recruitment of monocytes/peritoneal macrophage and cytokine response to bacterial products in vivo
physiological function
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anti-inflammatory and tissue-protective role of 12/15-LO and its eicosanoidic products during chronic inflammatory disorders such as arthritis. 12/15-LO-deficient mice show enhanced inflammatory gene expression and decreased levels of the eicosanoid lipoxin A(4) within their inflamed synovia. 12/15-LO-deficient macrophages display significantly reduced levels of lipoxin A(4), which correlate with increased activation of p38MAPK and an enhanced inflammatory gene expression after stimulation with TNF-alpha
physiological function
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12/15-LOX is the central executioner in an oxidative stress-related neuronal death program. In neuronal HT22 cells subjected to glutamate-induced oxidative stress, 12/15-LOX damages mitochondria, which represents the committed step that condemns the cell to die. Mitochondria incubated with 12/15-LOX generate reactive oxygen species
physiological function
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possibility of 12-LOX involvement in ceramide-mediated generation of reactive oxygen species and cellular oxidative stress
physiological function
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12/15LO expression increases chemokine production. 2/15LO mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding. Adipose tissue from high fat diet-fed 12/15LO KO mice is not infiltrated by macrophages and does not display any increase in the inflammatory markers compared to adipose tissue from normal chow-fed mice. 12/15LO KO mice exhibit no high fat diet-induced change in insulin-stimulated glucose disposal rate or hepatic glucose output. Insulin-stimulated Akt phosphorylation in muscle tissue from high fat diet-fed mice is significantly greater in 12/15LO KO mice than in wild-type mice
physiological function
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ALOX15B might play a major role in human atherosclerosis
physiological function
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12-LOX mediates the MMP9 secretion via activation of PI3K/Akt/NF-kappaB
physiological function
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PDGF-induced STAT3 phosphorylation in primary human aortic smooth muscle cells requires the activity of 15-LO
physiological function
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12/15-lipoxygenase contributes to PDGF-induced activation of STAT3
physiological function
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inhibition of 12-LOX activity inhibits platelet aggregation, which is coupled to a significant shift in the ability of the platelet to induce normal integrin activation, dense granule secretion, and platelet adhesion under venous shear
physiological function
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12/15LO expression increases chemokine production. 2/15LO mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding. Adipose tissue from high fat diet-fed 12/15LO KO mice is not infiltrated by macrophages and does not display any increase in the inflammatory markers compared to adipose tissue from normal chow-fed mice. 12/15LO KO mice exhibit no high fat diet-induced change in insulin-stimulated glucose disposal rate or hepatic glucose output. Insulin-stimulated Akt phosphorylation in muscle tissue from high fat diet-fed mice is significantly greater in 12/15LO KO mice than in wild-type mice
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physiological function
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12/15-LOX is a critical mediator of the chronic type 1 inflammatory response. Evolution of the immune response to Toxoplasma gondii is accompanied by an increasing requirement for 12/15-LOX mediated signaling. Although 12/15-LOX deficient mice are resistant to acute Toxoplasma gondii infection, 80% of 12/15-LOX-deficient mice die during chronic toxoplasmosis, compared to no deaths in wild-type controls. The enhanced susceptibility of 12/15-LOX-deficient mice to chronic toxoplasmosis is associated with reduced production of IL-12 and gamma interferon (IFN-gamma) that is not evident during acute infection. Ex vivo IFN-gamma production by 12/15-LOX-deficient splenocytes can be rescued by the addition of recombinant IL-12. 12/15-LOX does not play a role in macrophage killing of Toxoplasma gondii in vitro; endogenous 12/15-LOX defines the resident peritoneal macrophage population and regulates both the recruitment of monocytes/peritoneal macrophage and cytokine response to bacterial products in vivo; the 12/15-LO pathway participates in the regulation of monocyte chemoattractant protein-1 expression in mouse macrophages
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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
1-linoleoyl lysophosphatidic acid + O2
(S)-hydroperoxy 1-linoleoyl lysophosphatidic acid
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i.e. linoleoyl-lysoPA
major product
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?
1-linoleoyl lysophosphatidylcholine + O2
(S)-hydroperoxy 1-linoleoyl lysophosphatidylcholine
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i.e. linoleoyl-lysoPC
major product
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?
2 arachidonate + 2 O2 + 2 H+
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate + (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate + H2O
20-hydroxyeicosatetraenoic acid methyl ester + O2
8,20-dihydroxyeicosatetraenoic acid + 12,20-dihydroxyeicosatetraenoic acid + 9,20-dihydroxyeicosatetraenoic acid
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-
-
-
?
4,7,10,13,16,19-docosahexaenoic acid + O2
14-hydroxy-4,7,10,12,16,19-docosahexaenoic acid
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activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
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?
4,7,10,13,16,19-docosahexaenoic acid + O2
14-hydroxy-4,7,10,13,16,19-docosahexaenoic acid
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-
-
-
?
5(S)-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid + O2
5,12-(5S,12S)-dihydroxy-6E,8Z,10E,14Z-eicosatetraenoic acid + 5,12-(5S,15S)-dihydroxy-6E,8Z,11Z,13E-eicosatetraenoic acid
5,15-(5S,15S)-dihydroperoxyarachidonic acid + O2
5S,14R,15S-trihydroperoxy-6,10,12-trans-8-cis-eicosatetraenoic acid
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the product is reduced to 5S,14R,15S,-8-cis-lipoxin B due to 14R-oxygenase activity of the enzyme
?
5,8,11-eicosatrienoic acid + O2
12-hydroxy-5,8,10-eicosatrienoic acid
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activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
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?
6,9,12-octadecatrienoic acid + O2
13-hydroxy-6,9,12-octadecatrienoic acid
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?
alpha-linolenic acid + O2
13-hydroxy-(9Z,11E,15Z)-octadecatrienoic acid
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?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
arachidonic acid + O2
(12R)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoic acid
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the mutant enzyme G441A converts arachidonic acid to 8S-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid and 12R-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid in a 1.4:1 ratio
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?
arachidonic acid methyl ester + O2
12-hydroxyeicosatetraenoic acid methyl ester
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activity with (12R)-lipoxygenase and epidermal-type-(12S)-lipoxygenase, no activity with platelet-type (12S)-lipoxygenase
epidermal-type (12S)-lipoxygenase produces only 12-hydroxyeicosatetraenoic acid methyl ester, (12R)-lipoxygenase produces (12R)-hydroxyeicosatetraenoic acid methyl ester and (4R)-hydroxyeicosatetraenoic acid methyl ester
?
gamma linolenic acid + O2
10-hydroxy-octadeca-(6Z,8E,12Z)-trienoic acid
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poor substrate
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?
gamma-linolenic acid + O2
10-hydroxy-octadeca-(6Z,8E,12Z)-trienoic acid
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?
linoleic acid + O2
13(S)-hydroxy-(9Z,11E)-octadecadienoic acid
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?
linoleic acid methyl ester + O2
(9R)-hydroxyoctadecadienoic acid methyl ester
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?
linoleic acid methyl ester + O2
13(S)-hydro(pero)xyoctadecadienoic acid methyl ester
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activity with epidermal-type (12S)-lipoxygenase, no activity with platelet-type (12S)-lipoxygenase and (12R)-lipoxygenase
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?
methyl arachidonate + O2
(15S,5Z,8Z,11Z,13E)-15-hydroxy-5,8,11,13-eicosatetraenoic acid methyl ester
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?
11,14,17-eicosatrienoic acid + O2
?
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leukocyte enzyme: 28% of the activity with arachidonic acid, platelet enzyme: less than 2% of the activity with arachidonic acid
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?
11,14,17-eicosatrienoic acid + O2
?
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no activity with enzyme from platelet
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?
11,14-eicosadienoic acid + O2
?
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leukocyte enzyme: 15% of the activity with arachidonic acid, platelet enzyme: less than 2% of the activity with arachidonic acid
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?
2 arachidonate + 2 O2 + 2 H+
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate + (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate + H2O
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(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate increases expression of monocyte chemoattractant protein MCP-1 in macrophages, also but less by 15(S)-hydroxyeicosatetranoic acid, and 12(S)-HETE activates NADPH oxidase, overview, i.e. 12(S)-HPETE and 12(S)-HETE, the first is the predominant product
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?
2 arachidonate + 2 O2 + 2 H+
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate + (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate + H2O
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(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate increases expression of monocyte chemoattractant protein MCP-1 in macrophages, also but less by 15(S)-hydroxyeicosatetranoic acid, and 12(S)-HETE activates NADPH oxidase, overview, i.e. 12(S)-HPETE and 12(S)-HETE, the first is the predominant product
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?
4,7,10,13,16,19-docosahexaenoic acid + O2
?
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leukocyte enzyme: 92% of the activity with arachidonic acid, platelet enzyme: 7% of the activity with arachidonic acid
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?
5(S)-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid + O2
5,12-(5S,12S)-dihydroxy-6E,8Z,10E,14Z-eicosatetraenoic acid + 5,12-(5S,15S)-dihydroxy-6E,8Z,11Z,13E-eicosatetraenoic acid
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enzyme from leukocyte, no activity with enzyme from platelet
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-
?
5(S)-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid + O2
5,12-(5S,12S)-dihydroxy-6E,8Z,10E,14Z-eicosatetraenoic acid + 5,12-(5S,15S)-dihydroxy-6E,8Z,11Z,13E-eicosatetraenoic acid
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leukocyte enzyme: 15% of the activity with arachidonic acid, platelet enzyme: less than 2% of the activity with arachidonic acid
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-
?
5(S)-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid + O2
5,12-(5S,12S)-dihydroxy-6E,8Z,10E,14Z-eicosatetraenoic acid + 5,12-(5S,15S)-dihydroxy-6E,8Z,11Z,13E-eicosatetraenoic acid
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weak activity
5S,12S-dihydroxy-6E,8Z,10E,14Z-eicosatetraenoic acid and 5S,15S-dihydroxy-6E,8Z,11Z,13E-eicosatetraenoic acid are produced in a ratio of about 8:2
?
5(S)-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid + O2
5,12-(5S,12S)-dihydroxy-6E,8Z,10E,14Z-eicosatetraenoic acid + 5,12-(5S,15S)-dihydroxy-6E,8Z,11Z,13E-eicosatetraenoic acid
-
-
-
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?
5(S)-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid + O2
5,12-(5S,12S)-dihydroxy-6E,8Z,10E,14Z-eicosatetraenoic acid + 5,12-(5S,15S)-dihydroxy-6E,8Z,11Z,13E-eicosatetraenoic acid
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40% of the activity with arachidonic acid
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-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
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-
-
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?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
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leukocyte enzyme: 73% of the activity with arachidonic acid, platelet enzyme: less than 94% of the activity with arachidonic acid
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-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
-
-
-
-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
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-
12-hydroxyeicosapentaenoic acid
-
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
-
-
-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
-
-
-
-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
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14% of the activity with arachidonic acid
-
-
?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
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leukocyte enzyme: 78% of the activity with arachidonic acid, platelet enzyme: 7% of the activity with arachidonic acid
-
-
?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
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dihomo-gamma-linolenic acid
-
-
?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
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activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
12-hydroxy-8,10,14-eicosatrienoic acid
?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
-
95% of the activity with arachidonic acid
-
-
?
alpha-linolenic acid + O2
?
-
leukocyte enzyme: 17% of the activity with arachidonic acid, platelet enzyme: less than 2% of the activity with arachidonic acid
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
further metabolized to (12S)-hydroxyeicosatetraenoate, which inhibits apoptosis in gastric cancer and activates ERK phosphorylation and the ERK1/2 signalling pathway, 12-LOX activates protein kinase C in AGS cells, overview
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
further metabolized to (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate, 12-HETE, has no effect on the spontaneous and lipopolysaccharide-stimulated growth of leukemic blasts
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
further metabolized to 12(S)-hydroxyeicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
i.e. 12(S)-HETE
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
12/15-LO protein levels and activity are increased in pathologically affected regions of Alzheimer’s disease brains, enzyme inhibition causes a decrease in amyloid-beta protein, 12/15-LO influences amyloid-beta protein precursor protein metabolism, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
arachidonic acid metabolization by lipoxygenases, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
the platelet-type 12S-lipoxygenase isozyme is involved in angiotensin-II induced signaling in vascular smooth muscle cells
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
regioselective oxidation is achieved through control over the position of hydrogen atom abstraction by the geometry and size of the enzyme active site and through control by the protein over the interaction of molecular oxygen with the generated delocalized substrate radical, analysis of catalytic mechanisms of lipoxygenases using 10,10-dideuterated arachidonic acid, 13,13-dideuterated arachidonic acid, and 0,10,13,13-d4-AA, overview
i.e. 12-HPETE, 12-hLO also forms small amounts of 11-HPETE, 8-HPETE, and 15-HPETE, overview
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
two molecules of arachidonic acid bind to one molecule of the enzyme, role of the PLAT domain in activity and membrane binding, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
high oxygen affinity is important for effective catalysis, L367 is involved in oxygen access, channel structure, overview, arachidonic acid closes the substrate-binding pocket for oxygen diffusion but opens a fourth oxygen access channel
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
further metabolized to (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
arachidonate induces cellular membrane disturbance and alters the mitochondrial membrane potential. 12-LOX is involved in covalent binding of alpha-naphthol to arachidonic acid in intact platelets, peroxidase-mediated co-oxidation with arachidonic acid, and peroxidase-mediated xenobiotic activation of alpha-naphthol cytotoxicity, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
arachidonic acid promotes the glutamate-induced cell death, reduces caspase-3 activity, and diminishes internucleosomal DNA fragmentation, it also reduces intracellular NAD, ATP and membrane potentials due to mitochondrila membrane dysfunction, and reduces the inhibitory effect of N-alpha-tosyl-L-phenylalanine chloromethyl ketone and 3,4-dichloroisocumarin on the glutamate-induced cell death, overview
is further metabolized to 12(S)-hydroxyeicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
poly(ADP-ribose) polymerase activation of 12-LOX, but not NADPH oxidase, following zinc release, might play an important role in reactive oxygen species generation and decrease of viability in glucose-reload-treated neurons, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
the enzyme is involved in production of biologically active lipid mediators, (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate, 13-HODE, and 13-HOTE, in the intestine of iron-deficient rats, the lipids are almoste absent in wild-type rats, overview
further metabolized to (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
15-H(p)ETE is the major reaction product independent of the pH
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
12-H(p)ETE is the major reaction product of 12/15-LOX independent of the pH
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
platelet-type (12S)-lipoxygenase produces (12S)-hydroxyeicosatetraenoic acid and (8R)-hydroxyeicosatetraenoic acid, epidermal-type (12S)-lipoxygenase produces only 12-hydroxyeicosatetraenoic acid
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
leukocyte-type enzyme produces 12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid, platelet-type enzyme produces only 12-hydroxyeicosatetraenoic acid
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
platelet-type (12S)-lipoxygenase produces (12S)-hydroxyeicosatetraenoic acid and (8R)-hydroxyeicosatetraenoic acid, epidermal-type (12S)-lipoxygenase produces only 12-hydroxyeicosatetraenoic acid
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid in the ratio of 6:1
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
12-monohydroxy derivatives + 14-monohydroxy derivatives + a mixture of the 8,11,12- and 10,11,12-trihydroxy products of arachidonic acid and 10,13,14- and 12,13,14-trihydroxy derivatives of docosahexaenoic acid
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
12/15LO eicosanoid products reduce cholesterol efflux to high density lipoproteins, regulate ATP-binding cassette transporter G1 expression and enhance ATP-binding cassette transporter G1 degradation and ATP-binding cassette transporter G1 serine phosphorylation
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
selective oxygenation at carbon 14 yields only the S-isomer
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
the 12-(S)-enantiomer is the predominant product
?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
mouse Alox12b protein, 12R-LOX, oxygenates arachidonate methyl ester rather than arachidonic acid to 12(R)-hydroperoxyeicosatetraenoic acid, HETE, and to 12(R)-HETE methyl ester
-
-
?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
mouse Alox12b protein, 12R-LOX, oxygenates arachidonate methyl ester rather than arachidonic acid to 12(R)-hydroperoxyeicosatetraenoic acid, HETE
-
-
?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
mouse Alox12b protein, 12R-LOX, oxygenates arachidonate methyl ester rather than arachidonic acid to 12(R)-hydroperoxyeicosatetraenoic acid, HETE, and to 12(R)-HETE methyl ester
-
-
?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
mouse Alox12b protein, 12R-LOX, oxygenates arachidonate methyl ester rather than arachidonic acid to 12(R)-hydroperoxyeicosatetraenoic acid, HETE
-
-
?
arachidonic acid + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonic acid + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
docosahexaenoic acid + O2
14-hydroxydocosahexaenoic acid
-
-
-
?
eicosapentaenoic acid + O2
12-hydroxyeicosapentaenoic acid
-
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
-
leukocyte enzyme: 32% of the activity with arachidonic acid, platelet enzyme: less than 2% of the activity with arachidonic acid
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
-
enzyme from leukocyte, no activity with enzyme from platelet
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
-
i.e. 6,9,12-octadecatrienoic acid
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
-
-
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
-
weak activity
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
-
101% of the activity with arachidonic acid
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
-
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
no activity with enzyme from platelet
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
enzyme from leukocyte
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
leukocyte enzyme: 11% of the activity with arachidonic acid, platelet enzyme: less than 2% of the activity with arachidonic acid
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
i.e. 9,12-octadecadienoic acid
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
-
-
-
-
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
no activity with enzyme from platelet
-
-
-
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
35% of the activity with arachidonic acid
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
enzyme from leukocyte
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
-
19% of the activity with arachidonic acid
-
-
?
15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid + O2
additional information
-
-
-
-
-
?
15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid + O2
additional information
-
-
leukocyte enzyme: 18% of the activity with arachidonic acid, platelet enzyme: 6% of the activity with arachidonic acid
-
-
?
15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid + O2
additional information
-
-
enzyme possesses 14,15-leukotriene A4 synthase activity, 8-oxygenase activity and 14-oxygenase activity
14R,15S-dihydroxy-5Z,8Z,10E,12E-eicosatetraenoic acid + 14S,15S-dihydroxy-5Z,8Z,10E,12E-eicosatetraenoic acid + 8S,15S-dihydroxy-5Z,9E,11Z,13E-eicosatetraenoic acid + 8R,15S-dihydroxy-5Z,9E,11Z,13E-eicosatetraenoic acid + 8R,15S-dihydroxy-5Z,9E,11E,13E-eicosatetraenoic acid + 8S,15S-dihydroxy-5Z,9E,11E,13E-eicosatetraenoic acid
?
15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid + O2
additional information
-
-
-
-
-
?
15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid + O2
additional information
-
-
-
14R,15S-dihydroxy-5Z,8Z,10E,12E-eicosatetraenoic acid + 14R,15S-epoxy-5Z,8Z,10E,12E-eicosatetraenoic acid
?
15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid + O2
additional information
-
-
-
(8S,15S)-dihydroperoxy-5Z,9E,11Z,13E-eicosatetraenoic acid + (14R,15S)-erythro-dihydroperoxy-5Z,8Z,10E,12E-eicosatetraenoic acid
?
additional information
?
-
-
no reaction with mead acid and methyl esters of linolenic acid and arachidonate
-
-
-
additional information
?
-
-
the 12-lipoxygenase pathway plays a critical role in angiogenesis
-
-
-
additional information
?
-
-
endogenous phospholipid hydroperoxide glutathione peroxidase plays a pivotal role in the regulation of 12(S)-lipoxygenase and cyclooxygenase 1 activities by reducing the level of intracellular lipid hydroperoxides in arachidonate metabolism in A431 cells
-
-
-
additional information
?
-
-
interaction between c-Jun and Sp1 may account for the functional regulation of 12(S)-lipoxygenase gene regulation. The direct and cooperative interaction between c-Jun and Sp1 induced by EGF or PMA activates the expression of the human 12(S)-lipoxygenase gene. Sp1 may serve at least in part as a carrier to bring c-Jun to the promoter, thus transactivating the transcriptional activity of the human 12(S)-lipoxygenase gene
-
-
-
additional information
?
-
-
the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the Alzheimer‘s disease brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder
-
-
-
additional information
?
-
-
12-lipoxygenase induces apoptosis of human gastric cancer AGS cells via the ERK1/2 signal pathway, overview
-
-
-
additional information
?
-
-
exogenously added arachidonic acid and 12(S)-hydroxyeicosatetraenoate, but not 12(R)-hydroxyeicosatetraenoate, as well as 2-arachidonoylglycerol increase invasion by PC-3 cancer cells, overview
-
-
-
additional information
?
-
-
a bifunctional enzyme exhibiting 12-lipoxygenase and 15-lipoxygenase, EC 1.13.11.33, activities
-
-
-
additional information
?
-
-
a bifunctional enzyme exhibiting 12-LO and 15-LO activity
-
-
-
additional information
?
-
product distributions of lipoxygenases under various conditions, overview
-
-
-
additional information
?
-
-
the 12-lipoxygenase pathway plays a critical role in angiogenesis
-
-
-
additional information
?
-
-
12-lipoxygenase metabolites of arachidonic acid mediate metabotropic glutamate receptor-dependent long-term depression at hippocampal CA3-CA1 synapses
-
-
-
additional information
?
-
-
increased expression of 12-LO has deleterius effects in beta cells
-
-
-
additional information
?
-
-
lipoxin A4 and docosahexaenoic acid-derived neuroprotectin D1 are lipid autacoids formed by 12/15-lipoxygenase pathway that exhibit anti-inflammatory and neuroprotective properties. The enzyme also shows action in wound healing that is distinct from the anti-inflammatory properties
-
-
-
additional information
?
-
Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
-
-
-
additional information
?
-
-
a bifunctional enzyme exhibiting 12-LO and 15-LO activity, the enzyme is also able to catalyze stereoselective oxidation of linoleic acid at position 13 over 9 to preferentially form 13(S)-hydroperoxyoctadienoic acid, which enhances MCP-1 expression, overview
-
-
-
additional information
?
-
-
reactive oxygen species formation catalyzed by 12-LOX
-
-
-
additional information
?
-
Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
-
-
-
additional information
?
-
-
a bifunctional enzyme exhibiting 12-LO and 15-LO activity, the enzyme is also able to catalyze stereoselective oxidation of linoleic acid at position 13 over 9 to preferentially form 13(S)-hydroperoxyoctadienoic acid, which enhances MCP-1 expression, overview
-
-
-
additional information
?
-
-
the bifunctional enzyme also forms (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyeicosa-5,8,11,13-tetraenoate, the product of 15-LO activity, EC 1.13.11.33, in a ratio of 9:1 15(S)-HPETE to 12(S)-HPETE
-
-
-
additional information
?
-
-
binding of allosteric effector [13(S)-hydroxyoctadeca-9(Z),11(E)-dienoic acid] shifts the monomer-dimer equilibrium toward dimer formation
-
-
-
additional information
?
-
-
the enzyme might, in a fast and effective way, be involved in the formation of signal and/or defense molecules thus contributing to the breoad resistance of mosses against pathogens
-
-
-
additional information
?
-
the enzyme might, in a fast and effective way, be involved in the formation of signal and/or defense molecules thus contributing to the breoad resistance of mosses against pathogens
-
-
-
additional information
?
-
-
the 12-lipoxygenase pathway plays a critical role in angiogenesis
-
-
-
additional information
?
-
intestinal leukocyte-type isozyme Alox15 shows poor or no 15-lipoxygenase activity, EC 1.13.11.33
-
-
-
additional information
?
-
-
enzyme shows 14R-oxygenase activity and 14,15-leukotriene A synthase activity
-
-
-
additional information
?
-
-
stereo-selectivity in LOX-catalyzed oxygenation of lysophospholipids, overview
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
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
2 arachidonate + 2 O2 + 2 H+
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate + (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate + H2O
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
2 arachidonate + 2 O2 + 2 H+
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate + (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate + H2O
-
-
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate increases expression of monocyte chemoattractant protein MCP-1 in macrophages, also but less by 15(S)-hydroxyeicosatetranoic acid, and 12(S)-HETE activates NADPH oxidase, overview
-
?
2 arachidonate + 2 O2 + 2 H+
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate + (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate + H2O
-
-
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate increases expression of monocyte chemoattractant protein MCP-1 in macrophages, also but less by 15(S)-hydroxyeicosatetranoic acid, and 12(S)-HETE activates NADPH oxidase, overview
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
P18054
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
further metabolized to (12S)-hydroxyeicosatetraenoate, which inhibits apoptosis in gastric cancer and activates ERK phosphorylation and the ERK1/2 signalling pathway, 12-LOX activates protein kinase C in AGS cells, overview
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
further metabolized to (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate, 12-HETE, has no effect on the spontaneous and lipopolysaccharide-stimulated growth of leukemic blasts
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
further metabolized to 12(S)-hydroxyeicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
12/15-LO protein levels and activity are increased in pathologically affected regions of Alzheimer’s disease brains, enzyme inhibition causes a decrease in amyloid-beta protein, 12/15-LO influences amyloid-beta protein precursor protein metabolism, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
P18054
arachidonic acid metabolization by lipoxygenases, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
the platelet-type 12S-lipoxygenase isozyme is involved in angiotensin-II induced signaling in vascular smooth muscle cells
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
Q02759
arachidonate induces cellular membrane disturbance and alters the mitochondrial membrane potential. 12-LOX is involved in covalent binding of alpha-naphthol to arachidonic acid in intact platelets, peroxidase-mediated co-oxidation with arachidonic acid, and peroxidase-mediated xenobiotic activation of alpha-naphthol cytotoxicity, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
arachidonic acid promotes the glutamate-induced cell death, reduces caspase-3 activity, and diminishes internucleosomal DNA fragmentation, it also reduces intracellular NAD, ATP and membrane potentials due to mitochondrila membrane dysfunction, and reduces the inhibitory effect of N-alpha-tosyl-L-phenylalanine chloromethyl ketone and 3,4-dichloroisocumarin on the glutamate-induced cell death, overview
is further metabolized to 12(S)-hydroxyeicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
poly(ADP-ribose) polymerase activation of 12-LOX, but not NADPH oxidase, following zinc release, might play an important role in reactive oxygen species generation and decrease of viability in glucose-reload-treated neurons, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
Q02759
the enzyme is involved in production of biologically active lipid mediators, (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate, 13-HODE, and 13-HOTE, in the intestine of iron-deficient rats, the lipids are almoste absent in wild-type rats, overview
further metabolized to (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
O70582
mouse Alox12b protein, 12R-LOX, oxygenates arachidonate methyl ester rather than arachidonic acid to 12(R)-hydroperoxyeicosatetraenoic acid, HETE, and to 12(R)-HETE methyl ester
-
-
?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
O70582
mouse Alox12b protein, 12R-LOX, oxygenates arachidonate methyl ester rather than arachidonic acid to 12(R)-hydroperoxyeicosatetraenoic acid, HETE, and to 12(R)-HETE methyl ester
-
-
?
additional information
?
-
-
the 12-lipoxygenase pathway plays a critical role in angiogenesis
-
-
-
additional information
?
-
-
endogenous phospholipid hydroperoxide glutathione peroxidase plays a pivotal role in the regulation of 12(S)-lipoxygenase and cyclooxygenase 1 activities by reducing the level of intracellular lipid hydroperoxides in arachidonate metabolism in A431 cells
-
-
-
additional information
?
-
-
interaction between c-Jun and Sp1 may account for the functional regulation of 12(S)-lipoxygenase gene regulation. The direct and cooperative interaction between c-Jun and Sp1 induced by EGF or PMA activates the expression of the human 12(S)-lipoxygenase gene. Sp1 may serve at least in part as a carrier to bring c-Jun to the promoter, thus transactivating the transcriptional activity of the human 12(S)-lipoxygenase gene
-
-
-
additional information
?
-
-
the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the Alzheimer‘s disease brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder
-
-
-
additional information
?
-
-
12-lipoxygenase induces apoptosis of human gastric cancer AGS cells via the ERK1/2 signal pathway, overview
-
-
-
additional information
?
-
-
exogenously added arachidonic acid and 12(S)-hydroxyeicosatetraenoate, but not 12(R)-hydroxyeicosatetraenoate, as well as 2-arachidonoylglycerol increase invasion by PC-3 cancer cells, overview
-
-
-
additional information
?
-
-
the 12-lipoxygenase pathway plays a critical role in angiogenesis
-
-
-
additional information
?
-
-
12-lipoxygenase metabolites of arachidonic acid mediate metabotropic glutamate receptor-dependent long-term depression at hippocampal CA3-CA1 synapses
-
-
-
additional information
?
-
-
increased expression of 12-LO has deleterius effects in beta cells
-
-
-
additional information
?
-
-
lipoxin A4 and docosahexaenoic acid-derived neuroprotectin D1 are lipid autacoids formed by 12/15-lipoxygenase pathway that exhibit anti-inflammatory and neuroprotective properties. The enzyme also shows action in wound healing that is distinct from the anti-inflammatory properties
-
-
-
additional information
?
-
O70582
Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
-
-
-
additional information
?
-
O70582
Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
-
-
-
additional information
?
-
-
the enzyme might, in a fast and effective way, be involved in the formation of signal and/or defense molecules thus contributing to the breoad resistance of mosses against pathogens
-
-
-
additional information
?
-
Q70EX8
the enzyme might, in a fast and effective way, be involved in the formation of signal and/or defense molecules thus contributing to the breoad resistance of mosses against pathogens
-
-
-
additional information
?
-
-
the 12-lipoxygenase pathway plays a critical role in angiogenesis
-
-
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Fe2+
Iron
Ca2+
-
not essential for activity, partially purified enzyme is stimulated approximately 2fold in the presence of 0.1-5.0 mM Ca2+
Fe2+
required for the catalytic cycle of fatty acid oxidation by lipoxygenase, overview
Fe2+
-
0.94 atoms of iron per molecule. Loss of the mass of an iron atom from the protein as the pH is lowered from 5 to 4. The iron goes through acid-induced unfolding accompanied by the appearance of an iron-free intermediate that retains a native conformation
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
11-thialinoleic acid
-
is a competitive inhibitor of 12-lipoxygenase with arachidonate as substrate. Presence of inhibitor does not alter the product distribution for 12-lipoxygenase. It does not change the regioselectivity of 12-lipoxygenase
2,2'-dipyridyl
-
1 mM, 87% inactivation, no reactivation by addition of excess Fe2+ or Fe3+
2,6-dibromo-4-[1-(3-bromo-4-hydroxyphenyl)-1-methylethyl]phenol
-
IC50: 0.007 mM
3-[3-bromo-5-(2,6-dibromo-4-{2-[2-(3-bromo-4-hydroxy-phenyl)-ethylcarbamoyl]-2-[(E)-hydroxyimino]-ethyl}-phenoxy)-4-methyl-phenyl]-N-[(E)-2-(3,5-dibromo-4-hydroxy-phenyl)-vinyl]-2-[(E)-hydroxyimino]-propionamide
-
IC50: 0.0004 mM
4-[5-(1H-indol-3-yl)-3-trifluoromethyl-4,5-dihydropyrazol-1-yl]-benzenesulfonamide
-
0.01 mM inhibits LOX-12 by 5%
4-[5-(7-chloro-1H-indol-3-yl)-3-trifluoromethyl-4,5-dihydropyrazol-1-yl]-benzenesulfonamide
-
0.01 mM inhibits LOX-12 by 3%
alpha-mangostin
-
NSC30552, a natural product, caspase-3 pathway inhibitor, performs selective inhibition of 12-LO
esculetine
-
inhibits the enzyme and its binding to cytoplasmic muscle fibrills, overview
GT-E
-
100 mM, dried radix of Glycine tomentella freeze-dried to a powder, IC50: 0.00072 mg/ml
-
michellamine B
-
NSC661755, potent but non-selective inhibitor, a natural anti-viral agent
N-([5-chloro-2-(dimethylamino)-8-hydroxyquinolin-7-yl](furan-2-yl)methyl)acetamide
-
-
N-([5-chloro-8-hydroxy-2-(piperidin-1-yl)quinolin-7-yl](furan-2-yl)methyl)acetamide
-
-
N-[(5-chloro-8-hydroxy-1,2,3,4,4a,8a-hexahydroquinolin-7-yl)(furan-2-yl)methyl]propanamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(5-methylthiophen-2-yl)methyl]propanamide
-
-
neodysidenin
-
natural product from marine sponge Dysidea herbacea from Papua New Guinea, extraction and purification, overview, steady-state inhibition kinetics, competitive mode of inhibition, selective for 12-LO
siRNA
-
inhibition of p12-LOX in JB6 P+ cells by siRNA transfection, causes a significant suppression of 12-O-tetradecanoylphorbol-13-acetate-induced neoplastic transformation by 61% compared with that in control cells
-
4-(2-oxapentadeca-4-yne)phenylpropanoic acid
-
mixed type inhibition towards the ferric form of 12-lipoxygenase
4-(2-oxapentadeca-4-yne)phenylpropanoic acid
-
shows the oxidation of the inactive ferrous enzyme to the active ferric enzyme and competes with arachidonic acid for the ferric enzyme
AA861
-
prevents cell death, the 12/15-LOX inhibitor and the proteasome protect against exogenous glutamate, but not by preventing glutathione depletion. LOX inhibition, but not proteasome inhibition, reduces oxidative stress in glutamate-treated HT22 cells. The mitochondrial membrane potential is protected by coinhibition with baicalien
arachidonic acid
-
inhibits reaction with 5-hydroxy-6,8,11,14-eicodatetraenoic acid
baicalein
-
inhibits the enzyme and its binding to cytoplasmic muscle fibrills, overview
baicalein
-
inhibition of 12-LOX enzymatic activity using baicalein inhibits MMP9 expression in PC3 cells
baicalein
-
p12-LOX specific inhibitor, suppresses proliferation of JB6 P+ cells when cells are seeded at a low density in a culture plate by 81%
baicalein
-
prevents cell death, the 12/15-LOX inhibitor and the proteasome protect against exogenous glutamate, but not by preventing glutathione depletion. LOX inhibition, but not proteasome inhibition, reduces oxidative stress in glutamate-treated HT22 cells. The mitochondrial membrane potential is protected by coinhibition with AA861
PD146176
-
selective inhibitor of 12/15-LOX, macrophages treated with PD146176 elaborate reduced levels of interleukin-12 in response to Toxoplasma gondii antigen
additional information
-
development of an assay method for high throughput screening of libraries for platelet-type 12-hLO selective inhibitors, four organo-mercurial compounds with NCI library IDs NSC20410, NSC268879, NSC321237, and NSC321239, are also found to be selectively inhibitory, but not pursued further due to their potentially toxic side effects, overview
-
additional information
-
comparison of structural requirements for flavonoid inhibitory potency and selectivity against platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2, the two latter belong to EC 1.13.11.33, overview, catechols are essential for high potency, isoflavones and isoflavanones tend to select against 12-hLO, isoflavans tend to select against isozyme 15-hLO-1, but few flavonoids target isozyme 15-hLO-2, molecular modeling analysis, overview
-
additional information
-
the histone deacetylase inhibitor trichostatin A inhibits EGF-induced 12(S)-lipoxygenase expression via downregulation of c-Jun and Sp1 expression, enhancement of Sp1 acetylation, and inhibition of Sp1, c-Jun, and p300 recruitment to the gene promoter of 12-LO, overview
-
additional information
-
enzyme inhibition causes a decrease in amyloid-beta protein
-
additional information
-
0.01 mM 4-[5-(6-chloro-1H-indol-3-yl)-3-trifluoromethyl-4,5-dihydropyrazol-1-yl]-benzenesulfonamide or rofecoxib do not inhibit LOX-12
-
additional information
-
physico-chemical state of the substrate and the complex equilibrium between fatty acid monomers, acid soaps and micelles may impact the reaction specificity of LOX-isoforms
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
alpha-Naphthol
slight activation of enzyme activity at 0.25 mM, but not at 0.5 mM
additional information
-
the enzyme is induced by the epidermal growth factor, EGF
-
additional information
-
a significant increase of 12-lipoxygenase enzyme activity in presence of arachidonic acid under GSH depletion induced by glutamate in C6 glimoa cells, overview
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0072
arachidonic acid
-
cytosolic hp-12LOX, pH 7.4, recombinant wild-type enzyme
0.0087
arachidonic acid
-
membrane hp-12LOX, pH 7.4, recombinant wild-type enzyme
0.009
O2
-
pH 7.4, mutant L367E, with substrate linoleic acid; pH 7.4, mutant L367K, with substrate linoleic acid
additional information
additional information
-
kinetics with lysophospholipid substrates
-
additional information
additional information
-
dependence of the recombinant His-tagged isozyme hp-12LOX enzymatic reaction rate on the concentration of arachidonic acid and pH, kinetics, overview
-
additional information
additional information
-
free-energy distribution for oxygen inside the substrate-free rabbit 12/15-LOX, containing four nested free-energy isosurfaces with different energy levels, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.002
4-(2-oxapentadeca-4-yne)phenylpropanoic acid
-
inhibition of the ferric form of 12-lipoxygenase, free enzyme
0.0045
4-(2-oxapentadeca-4-yne)phenylpropanoic acid
-
inhibition of the ferric form of 12-lipoxygenase, substrate-bound form of enzyme
0.07
4-(2-oxapentadeca-4-yne)phenylpropanoic acid
-
inhibition of the ferrous form of 12-lipoxygenase
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0041
2,3,4,5-tetrabromo-6-(4,5-dibromo-2-hydroxyphenoxy)phenol
Homo sapiens;
-
IC50: 0.0041 mM
0.00041
2,3,5-tribromo-6-(4,5-dibromo-2-hydroxyphenoxy)phenol
Homo sapiens;
-
IC50: 0.00041 mM
0.007
2,6-dibromo-4-[1-(3-bromo-4-hydroxyphenyl)-1-methylethyl]phenol
Homo sapiens;
-
IC50: 0.007 mM
0.0004
3-[3-bromo-5-(2,6-dibromo-4-{2-[2-(3-bromo-4-hydroxy-phenyl)-ethylcarbamoyl]-2-[(E)-hydroxyimino]-ethyl}-phenoxy)-4-methyl-phenyl]-N-[(E)-2-(3,5-dibromo-4-hydroxy-phenyl)-vinyl]-2-[(E)-hydroxyimino]-propionamide
Homo sapiens;
-
IC50: 0.0004 mM
0.075
N-([5-chloro-2-(dimethylamino)-8-hydroxyquinolin-7-yl](furan-2-yl)methyl)acetamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.075
N-([5-chloro-8-hydroxy-2-(piperidin-1-yl)quinolin-7-yl](furan-2-yl)methyl)acetamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.075
N-[(2,5-dichloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.075
N-[(4-chloro-1-hydroxynaphthalen-2-yl)(furan-2-yl)methyl]acetamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.002
N-[(5-bromo-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
Homo sapiens;
-
pH 8.0, 23°C
0.002
N-[(5-bromo-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.001
N-[(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
Homo sapiens;
-
pH 8.0, 23°C
0.014
N-[(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.075
N-[(5-bromofuran-2-yl)(5-chloro-8-hydroxyquinolin-7-yl)methyl]propanamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.003
N-[(5-chloro-8-hydroxy-1,2,3,4,4a,8a-hexahydroquinolin-7-yl)(furan-2-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.05
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-fluorophenyl)methyl]propanamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.15
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]propanamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.0035
N-[(5-chloro-8-hydroxyquinolin-7-yl)(5-methylthiophen-2-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.003
N-[(5-chloro-8-hydroxyquinolin-7-yl)(cyclopropyl)methyl]acetamide
Homo sapiens;
-
pH 8.0, 23°C
0.0016
N-[(5-chloro-8-hydroxyquinolin-7-yl)(cyclopropyl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.025
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]-4-methylbenzamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.003
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
Homo sapiens;
-
pH 8.0, 23°C
0.025
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]benzamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.001
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.001
N-[(5-chloro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
Homo sapiens;
-
pH 8.0, 23°C
0.001
N-[(5-chloro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.15
N-[(5-chloro-8-hydroxyquinolin-7-yl)methyl]acetamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.075
N-[(5-chloro-8-methoxyquinolin-7-yl)(furan-2-yl)methyl]propanamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.005
N-[(5-fluoro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
Homo sapiens;
-
pH 8.0, 23°C
0.002
N-[(5-fluoro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
Homo sapiens;
-
pH 8.0, 23°C
0.0008
N-[(8-hydroxy-5-nitroquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.0034
N-[(8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.025
N-[(R)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
Homo sapiens;
-
pH 8.0, 23°C
0.025
N-[(R)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.00043
N-[(S)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
Homo sapiens;
-
pH 8.0, 23°C
0.00038
N-[(S)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.0026
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)-2-methylpropyl]acetamide
Homo sapiens;
-
pH 8.0, 23°C
0.0012
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)-2-methylpropyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
0.15
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)ethyl]acetamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.05
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)ethyl]propanamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.075
N-[1-(5-fluoro-8-hydroxyquinolin-7-yl)ethyl]acetamide
Homo sapiens;
-
value above, pH 8.0, 23°C
0.0012
N-[furan-2-yl(8-hydroxy-5-nitroquinolin-7-yl)methyl]propanamide
Homo sapiens;
-
pH 8.0, 23°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.3
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.5
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.1 - 8.6
-
pH 6.1: 37% of maximal activity, pH 8.6: 44% of maximal activity
6.3 - 8.8
-
pH 6.3: about 70% of maximal activity, pH 8.8: about 40% of maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
induced by a Ca2+ ionophore, from acute myeloid leukemic and acute lymphoid leukemic patients, upregulation of the enzyme, quantitative expression analysis
-
expression of both platelet and leukocyte-type 12-lipoxygenase in distal convoluted tubule cell line. mDCT cells show an active 12-LOX metabolism that appears to be modulated by cAMP and vasopressin
-
vascular smooth muscle, the enzyme associates with alpha-actin fibers
-
umbilical artery, the enzyme associates with alpha-actin fibers
additional information
-
the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the Alzheimer‘s disease brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder
-
12/15-LOX is selectively enhanced in the periphery, 12/15-LOX-expressing myeloid cells are enriched in the brain during chronic toxoplasmosis
-
12/15-LOX is selectively enhanced in the periphery, 12/15-LOX-expressing myeloid cells are enriched in the brain during chronic toxoplasmosis
-
-
most tumors show constitutive overexpression of platelet-type mRNA, leukocyte-type specific transcripts are detectable only in a few tumors
-
umbelical vein endothelial cells and foreskin dermal microvascular endothelial cells
-
platelet-type enzyme is the 12-lipoxygenase isoform responsible for the generation of most of the 12-hydroxyeicosateteaenoic acid
-
-
395399, 395400, 395403, 395406, 395408, 395409, 395410, 395425, 395428, 395429, 395431, 685330, 701926
-
enzyme activity is attributed predominantly to the neutrophils appearing in sinusoidal cavities rather than the non-parechymal cells
-
12/15-LOX is a macrophage-selective regulator of interleukin-12 production
macrophages that overexpress 12/15LO have reduced ATP-binding cassette G1 expression, increased transporter phosphorylation, and reduced cholesterol efflux
-
12/15-LOX is expressed by 95% of resident peritoneal CD11bhigh cells, with the remaining 5% being 12/15-LOX-. 12/15-LOX+ cells are phenotypically defined by high F4/80, SR-A, and Siglec1 expression, and enhanced IL-10 and G-CSF generation. In contrast, 12/15-LOX- cells are a dendritic cell population. Resident peritoneal macrophage numbers are significantly increased in 12/15-LOX-/- mice, suggesting alterations in migratory trafficking or cell differentiation in vivo
-
12/15-LOX is a macrophage-selective regulator of interleukin-12 production; 12/15-LOX is expressed by 95% of resident peritoneal CD11bhigh cells, with the remaining 5% being 12/15-LOX-. 12/15-LOX+ cells are phenotypically defined by high F4/80, SR-A, and Siglec1 expression, and enhanced IL-10 and G-CSF generation. In contrast, 12/15-LOX- cells are a dendritic cell population. Resident peritoneal macrophage numbers are significantly increased in 12/15-LOX-/- mice, suggesting alterations in migratory trafficking or cell differentiation in vivo; peritoneal
-
-
expression of platelet-type 12-LO, isozyme P-12-LO, and leukocyte-type 12-LO, isozyme L-12-LO
additional information
-
expression of p12-LOX is significantly higher in JB6P+ cells than in JB6P- cells that are resistant to transformation
additional information
the leukocyte-type isozyme is widely distributed in cell types, while the epidermis-type and the platelet-type isozymes are more limited
additional information
-
Plox-86 cells overexpress leukocyte-type 12/15-LO. Significant increase of monocyte chemoattractant protein-1 mRNA in Plox-86 cells
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
primarily associated with cytoplasmic vascular smooth muscle cell muscle fibrils binding to alpha-actin, a component of the cytoplasmic myofilaments, not associated with 12-LO serine or tyrosine phosphorylation, overview, the binding is induced by angiotensin II
-
membrane binding activities of wild-type platelet 12-lipoxygenase and mutant enzymes at pH 7.4, role of the PLAT domain membrane binding, overview
-
enzyme is expressed in a cryptic, microsomal-type form in primary culture epithelial cells, this form of enzyme may be selectively regulated by changes in cellular oxidation-reduction conditions dependent on cytosolic levels of GSH versus lipid hydroperoxide
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
72000
158000
-
about, recombinant His-tagged wild-type and mutant enzymes, gel filtration
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
dimer
-
binding of allosteric effector [13(S)-hydroxyoctadeca-9(Z),11(E)-dienoic acid] shifts the monomer-dimer equilibrium toward dimer formation. Enzyme dimerization may protect the enzyme from kinetic substrate inhibition by shielding the hydrophobic alpha2 helixes
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
low-resolution 16 A structure of enzyme in solution, dynamic light scattering and SAXS analysis of hp-12LOX shows that this enzyme as a whole is stable in the dimeric form, while mutants without PLAT domains associate into larger aggregates
-
crystals diffracting to high resolution (1.9 A) are obtained for a complex between the catalytic domain of leukocyte 12-lipoxygenase and the isoform-specific inhibitor, 4-(2-oxapentadeca-4-yne) phenylpropanoic acid (OPP)
-
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
rapid inactivation by the product hydroperoxy fatty acid, at low concentrations, 10-100 nM
50
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GENERAL STABILITY