Information on EC 1.13.11.31 - arachidonate 12-lipoxygenase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
1.13.11.31
-
RECOMMENDED NAME
GeneOntology No.
arachidonate 12-lipoxygenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dehydration
-
-
-
-
dioxygenation
-
-
-
-
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Arachidonic acid metabolism
-
-
arachidonic acid metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
arachidonate:oxygen 12-oxidoreductase
The product is rapidly reduced to the corresponding 12S-hydroxy compound.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
(12R)-lipoxygenase
-
-
11R-lipoxygenase
-
-
12(R)-lipoxygenase
-
-
12(S)-lipoxygenase
-
-
12-lipoxygenase
-
-
-
-
12-lipoxygenase
O75342
-
12-lipoxygenase
P18054
-
12-lipoxygenase
-
-
12-lipoxygenase
Mus musculus C57BL/6
-
-
-
12-lipoxygenase
-
-
12-lipoxygenase
Q02759
-
12-lipoxygenase
-
-
12-lipoxygenase
P16469
-
12-LO
-
-
12-LOX
-
-
-
-
12-LOX
-
-
12-LOX
Q02759
-
12/15 lipoxygenase
-
-
12/15 lipoxygenase
-
-
12/15-lipoxygenase
-
-
-
-
12/15-lipoxygenase
-
-
12/15-lipoxygenase
P39654
-
12/15-lipoxygenase
Mus musculus C57BL/6
-
-
-
12/15-lipoxygenase
-
-
12/15-lipoxygenase
-
-
12/15-lipoxygenase
-
-
12/15-lipoxygenases
-
-
12/15-LO
-
-
12/15-LO
Mus musculus C57BL/6
-
;
-
12/15-LO
-
-
12/15-LO
-
-
12/15-LOX
-
-
12/15-LOX
Mus musculus C57BL/6
-
;
-
12/15LO
-
-
12/15LO
P39654
-
12/15LO
Mus musculus C57BL6
-
-
-
12/15LO
-
-
12DELTA-lipoxygenase
-
-
-
-
12R-lipoxygenase
O70582
-
12R-lipoxygenase
Mus musculus A/J
O70582
-
-
12R-LOX
O75342
-
12R-LOX
O70582
-
12R-LOX
Mus musculus A/J
O70582
-
-
12R-LOX-2
-
-
12S-lipoxygenase
-
-
-
-
12S-lipoxygenase
-
-
2/15-lipoxygenase
-
-
2/15-lipoxygenase
Mus musculus C57BL6
-
-
-
Alox12b
O70582
-
Alox12b
Mus musculus A/J
O70582
-
-
Alox15
-
-
Alox15
Q02759
-
ALOX15B
-
-
ALOX5
-
-
C-12 lipoxygenase
-
-
-
-
DELTA 12-lipoxygenase
-
-
-
-
epidermal-type lipoxygenase
-
-
hp-12LOX
P18054
-
human platelet 12-lipoxygenase
P18054
-
leukocyte-type 12-lipoxygenase
-
-
leukocyte-type 12-LOX
-
-
leukocyte-type 12/15-lipoxygenase
-
-
leukocyte-type lipoxygenase
-
-
leukotriene A4 synthase M
-
-
-
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lipoxygenase 12
-
-
LOX-12
-
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LTA4 synthase
-
-
-
-
oygenase, arachidonate 12-lip-
-
-
-
-
P-12LOX
-
-
p12-LO
-
-
p12-LOX
-
-
platelet-type 12(S)-lipoxygenase
-
-
platelet-type 12-human lipoxygenase
P18054
-
platelet-type 12-lipoxygenase
-
-
platelet-type 12-lipoxygenase
-
-
platelet-type 12-LOX
-
-
Platelet-type lipoxygenase 12
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
82391-43-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
soft coral
-
-
Manually annotated by BRENDA team
gene ALOX15
-
-
Manually annotated by BRENDA team
isozyme 12-hLO
-
-
Manually annotated by BRENDA team
isozyme platelet 12-hLO
UniProt
Manually annotated by BRENDA team
isozymes P-12-LO and L-12-LO
-
-
Manually annotated by BRENDA team
platelet-type 12S-lipoxygenase isozyme
-
-
Manually annotated by BRENDA team
C57BL/6 mice
-
-
Manually annotated by BRENDA team
C57Bl6 mice
-
-
Manually annotated by BRENDA team
four 12-lipoxygenase: 1.platelet-type 12-lipoxygenase, 2. leukocyte-type lipoxygenase, 3. epidermal-type lipoxygenase, 4. 12(R)-lipoxygenase
-
-
Manually annotated by BRENDA team
strain A/J
UniProt
Manually annotated by BRENDA team
Mus musculus A/J
strain A/J
UniProt
Manually annotated by BRENDA team
Mus musculus C57BL/6
C57BL/6 mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BL6
C57Bl6 mice
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
UniProt
Manually annotated by BRENDA team
wild-type Sprague-Dawley rats and iron-deficient Belgrade rats, three isozymes: platelet, leukocyte, and epidermis isozyme, Alox15 is a leukocyte-type isozyme
UniProt
Manually annotated by BRENDA team
Zucker rat
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
P39654
macrophages that lack 12/15LO have enhanced transporter expression, reduced ATP-binding cassette G1 phosphorylation, and increased cholesterol efflux
malfunction
-
12-LOX inhibition attenuates platelet aggregation
malfunction
-
12-LOX-overexpressing PC-3 cells show an enhanced invasive ability which results from an increase in MMP9 expression and secretion
malfunction
-
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
-
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
-
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
-
12/15-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
-
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
-
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
P39654
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
-
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
-
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
-
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
-
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
-
possibility of 12-LOX involvement in ceramide-mediated generation of reactive oxygen species and cellular oxidative stress
physiological function
-
the 12/15-LO pathway participates in the regulation of monocyte chemoattractant protein-1 expression in mouse macrophages
physiological function
-
12-LOX mediates the MMP9 secretion via activation of PI3K/Akt/NF-kappaB
physiological function
-
12/15-lipoxygenase contributes to PDGF-induced activation of STAT3
physiological function
-
ALOX15B might play a major role in human atherosclerosis
physiological function
-
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
-
PDGF-induced STAT3 phosphorylation in primary human aortic smooth muscle cells requires the activity of 15-LO
physiological function
Mus musculus C57BL/6
-
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
-
physiological function
Mus musculus C57BL6
-
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
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(Z,Z,Z,E)-5,8,11,13-eicosatetraenoic acid + O2
?
show the reaction diagram
-
-
-
-
?
1-linoleoyl lysophosphatidic acid + O2
(S)-hydroperoxy 1-linoleoyl lysophosphatidic acid
show the reaction diagram
-
i.e. linoleoyl-lysoPA
major product
-
?
1-linoleoyl lysophosphatidylcholine + O2
(S)-hydroperoxy 1-linoleoyl lysophosphatidylcholine
show the reaction diagram
-
i.e. linoleoyl-lysoPC
major product
-
?
11,14,17-eicosatrienoic acid + O2
?
show the reaction diagram
-
-
-
-
?
11,14,17-eicosatrienoic acid + O2
?
show the reaction diagram
-
poor substrate
-
-
?
11,14,17-eicosatrienoic acid + O2
?
show the reaction diagram
-
no activity with enzyme from platelet
-
-
?
11,14,17-eicosatrienoic acid + O2
?
show the reaction diagram
-
enzyme from leukocyte
-
-
-
11,14,17-eicosatrienoic acid + O2
?
show the reaction diagram
-
enzyme from leukocyte
-
-
?
11,14,17-eicosatrienoic acid + O2
?
show the reaction diagram
-
leukocyte enzyme: 28% of the activity with arachidonic acid, platelet enzyme: less than 2% of the activity with arachidonic acid
-
-
?
11,14-eicosadienoic acid + O2
?
show the reaction diagram
-
-
-
-
?
11,14-eicosadienoic acid + O2
?
show the reaction diagram
-
no activity with enzyme from platelet
-
-
-
11,14-eicosadienoic acid + O2
?
show the reaction diagram
-
no activity with enzyme from platelet
-
-
?
11,14-eicosadienoic acid + O2
?
show the reaction diagram
-
enzyme from leukocyte
-
-
?
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
show the reaction diagram
-
-
(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
-
?
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
show the reaction diagram
Mus musculus C57BL/6
-
-
(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
-
?
20-hydroxyeicosatetraenoic acid methyl ester + O2
8,20-dihydroxyeicosatetraenoic acid + 12,20-dihydroxyeicosatetraenoic acid + 9,20-dihydroxyeicosatetraenoic acid
show the reaction diagram
-
-
-
-
?
4,7,10,13,16,19-docosahexaenoic acid + O2
?
show the reaction diagram
-
-
-
-
?
4,7,10,13,16,19-docosahexaenoic acid + O2
?
show the reaction diagram
-
-
-
-
?
4,7,10,13,16,19-docosahexaenoic acid + O2
?
show the reaction diagram
-
leukocyte enzyme: 92% of the activity with arachidonic acid, platelet enzyme: 7% of the activity with arachidonic acid
-
-
?
4,7,10,13,16,19-docosahexaenoic acid + O2
14-hydroxy-4,7,10,13,16,19-docosahexaenoic acid
show the reaction diagram
-
-
-
-
?
4,7,10,13,16,19-docosahexaenoic acid + O2
14-hydroxy-4,7,10,12,16,19-docosahexaenoic acid
show the reaction diagram
-
activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
-
?
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
show the reaction diagram
-
-
-
-
?
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
show the reaction diagram
-
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
show the reaction diagram
-
enzyme from leukocyte, no activity with enzyme from platelet
-
-
?
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
show the reaction diagram
-
leukocyte enzyme: 15% of the activity with arachidonic acid, platelet enzyme: less than 2% of the activity with arachidonic acid
-
-
?
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
show the reaction diagram
-
40% of the activity with arachidonic acid
-
-
?
5,15-(5S,15S)-dihydroperoxyarachidonic acid + O2
5S,14R,15S-trihydroperoxy-6,10,12-trans-8-cis-eicosatetraenoic acid
show the reaction diagram
-
-
the product is reduced to 5S,14R,15S,-8-cis-lipoxin B due to 14R-oxygenase activity of the enzyme
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
show the reaction diagram
-
-
-
-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
show the reaction diagram
-
-
-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
show the reaction diagram
-
-
-
-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
show the reaction diagram
-
-
-
-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
show the reaction diagram
-
-
12-hydroxyeicosapentaenoic acid
-
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
show the reaction diagram
-
leukocyte enzyme: 73% of the activity with arachidonic acid, platelet enzyme: less than 94% of the activity with arachidonic acid
-
-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
show the reaction diagram
-
14% of the activity with arachidonic acid
-
-
?
5,8,11-eicosatrienoic acid + O2
12-hydroxy-5,8,10-eicosatrienoic acid
show the reaction diagram
-
activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
-
?
6,9,12-octadecatrienoic acid + O2
13-hydroxy-6,9,12-octadecatrienoic acid
show the reaction diagram
-
-
-
?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
show the reaction diagram
-
-
-
?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
show the reaction diagram
-
-
-
-
?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
show the reaction diagram
-
-
-
-
?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
show the reaction diagram
-
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
show the reaction diagram
-
95% of the activity with arachidonic acid
-
-
?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
show the reaction diagram
-
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
show the reaction diagram
-
dihomo-gamma-linolenic acid
-
-
?
adrenic acid + O2
?
show the reaction diagram
-
-
-
-
?
alpha-linolenic acid + O2
?
show the reaction diagram
-
-
-
-
?
alpha-linolenic acid + O2
?
show the reaction diagram
-
-
-
-
?
alpha-linolenic acid + O2
?
show the reaction diagram
-
no activity with enzyme from platelet
-
-
-
alpha-linolenic acid + O2
?
show the reaction diagram
-
no activity with enzyme from platelet
-
-
?
alpha-linolenic acid + O2
?
show the reaction diagram
-
leukocyte enzyme: 17% of the activity with arachidonic acid, platelet enzyme: less than 2% of the activity with arachidonic acid
-
-
?
alpha-linolenic acid + O2
?
show the reaction diagram
-
activity with enzyme from leukocyte
-
-
?
alpha-linolenic acid + O2
13-hydroxy-(9Z,11E,15Z)-octadecatrienoic acid
show the reaction diagram
Q70EX8
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
Q70EX8
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
P39654
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
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
show the reaction diagram
-
-
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
show the reaction diagram
-
-
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
show the reaction diagram
-
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
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
the 12-(S)-enantiomer is the predominant product
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
Mus musculus C57BL/6
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
P18054
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
Q02759
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
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
show the reaction diagram
Q02759
-
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
show the reaction diagram
-
-
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
show the reaction diagram
-
-
further metabolized to 12(S)-hydroxyeicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
i.e. 12(S)-HETE
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
12/15-LO protein levels and activity are increased in pathologically affected regions of Alzheimers 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
show the reaction diagram
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
show the reaction diagram
P18054
arachidonic acid metabolization by lipoxygenases, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
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
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
P18054
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
show the reaction diagram
-
two molecules of arachidonic acid bind to one molecule of the enzyme, role of the PLAT domain in activity and membrane binding, overview
-
-
?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
show the reaction diagram
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, 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
show the reaction diagram
Mus musculus A/J
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, mouse Alox12b protein, 12R-LOX, oxygenates arachidonate methyl ester rather than arachidonic acid to 12(R)-hydroperoxyeicosatetraenoic acid, HETE
-
-
?
arachidonic acid + O2
12R-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid
show the reaction diagram
-
-
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
-
?
arachidonic acid + O2
?
show the reaction diagram
-
-
-
-
?
arachidonic acid + O2
?
show the reaction diagram
-
-
-
-
?
arachidonic acid + O2
(12S)-hydroperoxy-(5Z,8Z,11Z,13Z)-eicosatetraenoic acid
show the reaction diagram
-
-
-
-
?
arachidonic acid + O2
(12S)-hydroperoxy-(5Z,8Z,11Z,14Z)-eicosatetraenoic acid
show the reaction diagram
-
-
-
-
?
arachidonic acid methyl ester + O2
12-hydroxyeicosatetraenoic acid methyl ester
show the reaction diagram
-
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
?
dihomo-gamma linolenic acid + O2
?
show the reaction diagram
-
-
-
-
?
docosahexaenoic acid + O2
14-hydroxydocosahexaenoic acid
show the reaction diagram
Q70EX8
-
-
-
?
docosahexaenoic acid + O2
14-hydroxydocosahexaenoic acid
show the reaction diagram
-
-
-
-
?
eicosapentaenoic acid + O2
12-hydroxyeicosapentaenoic acid
show the reaction diagram
-
-
-
?
eicosapentaenoic acid + O2
12-hydroxyeicosapentaenoic acid
show the reaction diagram
Q70EX8
-
-
-
?
eicosapentaenoic acid + O2
12-hydroxyeicosapentaenoic acid
show the reaction diagram
-
-
-
-
?
gamma linolenic acid + O2
10-hydroxy-octadeca-(6Z,8E,12Z)-trienoic acid
show the reaction diagram
-
poor substrate
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
show the reaction diagram
-
-
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
show the reaction diagram
-
-
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
show the reaction diagram
-
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
show the reaction diagram
-
-
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
show the reaction diagram
-
weak activity
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
show the reaction diagram
-
101% of the activity with arachidonic acid
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
show the reaction diagram
-
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
show the reaction diagram
-
enzyme from leukocyte, no activity with enzyme from platelet
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
show the reaction diagram
-
i.e. 6,9,12-octadecatrienoic acid
-
-
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-(6Z,8E,12Z)-trienoic acid
show the reaction diagram
Q70EX8
-
-
-
?
linoleate + O2
(9Z,11E)-(13S)-13-hydroperoxyoctadeca-9,11-dienoate
show the reaction diagram
-
-
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
-
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
-
-
-
-
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
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
show the reaction diagram
-
no activity with enzyme from platelet
-
-
-
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
no activity with enzyme from platelet
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
enzyme from leukocyte
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
19% of the activity with arachidonic acid
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
35% of the activity with arachidonic acid
-
-
?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
-
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
show the reaction diagram
-
i.e. 9,12-octadecadienoic acid
-
-
?
linoleic acid + O2
?
show the reaction diagram
-
-
-
-
?
linoleic acid + O2
?
show the reaction diagram
-
4% of the activity with arachidonate
-
-
?
linoleic acid + O2
?
show the reaction diagram
-
reaction of EC 1.13.11.12
-
-
?
linoleic acid + O2
13(S)-hydroxy-(9Z,11E)-octadecadienoic acid
show the reaction diagram
Q70EX8
-
-
-
?
linoleic acid + O2
(9Z,11E)-(13S)-13-hydroperoxyoctadeca-9,11-dienoate
show the reaction diagram
-
-
-
-
?
linoleic acid methyl ester + O2
13(S)-hydro(pero)xyoctadecadienoic acid methyl ester
show the reaction diagram
-
activity with epidermal-type (12S)-lipoxygenase, no activity with platelet-type (12S)-lipoxygenase and (12R)-lipoxygenase
-
?
linoleic acid methyl ester + O2
(9R)-hydroxyoctadecadienoic acid methyl ester
show the reaction diagram
-
-
-
-
?
linolenic acid + O2
?
show the reaction diagram
-
poor substrate
-
-
?
methyl arachidonate + O2
(15S,5Z,8Z,11Z,13E)-15-hydroxy-5,8,11,13-eicosatetraenoic acid methyl ester
show the reaction diagram
-
-
-
-
?
11,14-eicosadienoic acid + O2
?
show the reaction diagram
-
leukocyte enzyme: 15% of the activity with arachidonic acid, platelet enzyme: less than 2% 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
-
-
-
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
?
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
?
methyl arachidonate + O2
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
enzyme shows 14R-oxygenase activity and 14,15-leukotriene A synthase activity, pathway of lipoxin biosynthesis
-
-
-
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
?
-
-
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
?
-
-
increased expression of 12-LO has deleterius effects in beta 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
?
-
-
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
?
-
-
the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the Alzheimers disease brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder
-
-
-
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
?
-
-
no reaction with mead acid and methyl esters of linolenic acid and arachidonate
-
-
-
additional information
?
-
-
12-lipoxygenase induces apoptosis of human gastric cancer AGS cells via the ERK1/2 signal pathway, overview
-
-
-
additional information
?
-
O70582
Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
-
-
-
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
?
-
-
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
?
-
Q02759
intestinal leukocyte-type isozyme Alox15 shows poor or no 15-lipoxygenase activity, EC 1.13.11.33
-
-
-
additional information
?
-
P18054
product distributions of lipoxygenases under various conditions, overview
-
-
-
additional information
?
-
-
stereo-selectivity in LOX-catalyzed oxygenation of lysophospholipids, 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
?
-
-
reactive oxygen species formation catalyzed by 12-LOX
-
-
-
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
?
-
Mus musculus C57BL/6
-
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
?
-
Mus musculus A/J
O70582
Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
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
show the reaction diagram
Mus musculus, Mus musculus C57BL/6
-
-
(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
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
P18054
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
-
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
show the reaction diagram
-
-
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
show the reaction diagram
-
-
further metabolized to 12(S)-hydroxyeicosatetraenoic acid
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
12/15-LO protein levels and activity are increased in pathologically affected regions of Alzheimers 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
show the reaction diagram
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
show the reaction diagram
P18054
arachidonic acid metabolization by lipoxygenases, overview
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
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
show the reaction diagram
-
the platelet-type 12S-lipoxygenase isozyme is involved in angiotensin-II induced signaling in vascular smooth muscle cells
-
-
?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
show the reaction diagram
Mus musculus, Mus musculus A/J
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
?
-
-
pathway of lipoxin biosynthesis
-
-
-
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
?
-
-
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
?
-
-
increased expression of 12-LO has deleterius effects in beta 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
?
-
-
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
?
-
-
the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the Alzheimers disease brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder
-
-
-
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
?
-
-
12-lipoxygenase induces apoptosis of human gastric cancer AGS cells via the ERK1/2 signal pathway, overview
-
-
-
additional information
?
-
O70582
Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
-
-
-
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
?
-
Mus musculus A/J
O70582
Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
not essential for activity, partially purified enzyme is stimulated approximately 2fold in the presence of 0.1-5.0 mM Ca2+
Ca2+
-
2 mM ATP + 1 mM CaCl2 stimulate approximately 2fold
Ca2+
-
stimulates
Ca2+
-
10 mM, required for activity
Ca2+
-
1 mM Ca2+-dependent activity
Fe2+
Q02759
dependent on
Fe2+
P18054
required for the catalytic cycle of fatty acid oxidation by lipoxygenase, overview
Fe2+
-
iron content of wild-type and mutant enzymes, 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
Fe2+
-
-
Fe3+
-
non-heme iron-containing enzyme
Iron
-
contains 0.7 gatom of non-heme iron per mol of enzyme
Iron
-
contains 0.7 Fe atoms per enzyme
Iron
-
enzyme contains iron
Mg2+
-
stimulates
Mn2+
-
stimulates
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+
2,3,4,5-tetrabromo-6-(2,4-dibromophenoxy)phenol
-
IC50: 0.0007 mM
2,3,4,5-tetrabromo-6-(4,5-dibromo-2-hydroxyphenoxy)phenol
-
IC50: 0.0041 mM
2,3,5-tribromo-6-(4,5-dibromo-2-hydroxyphenoxy)phenol
-
IC50: 0.00041 mM
2,4-dibromo-6-(2,4-dibromo-6-methoxyphenoxy)phenol
-
IC50: 0.012 mM
2,6-dibromo-4-[1-(3-bromo-4-hydroxyphenyl)-1-methylethyl]phenol
-
IC50: 0.007 mM
2-alkyl benzopyran-4-ones
-
weak inhibition
2-alkyl-6-hydroxy-4-H-benzopyran-4-one
-
weak inhibition
3'-chloro-7,8-dihydroxyisoflavone
-
-
3,15-dihydroxy-8,11,13-eicosatrienoic acid
-
IC50: 0.0075 mM
3,4,6,8-tetrabromooxanthren-1-ol
-
IC50: 0.05 mM
3,4,6-tribromo-2-(2,4-dibromophenoxy)phenol
-
IC50: 0.006 mM
3,4-dibromo-2-(5-bromo-2-hydroxyphenoxy)phenol
-
IC50: 0.047 mM
3,6,8-tribromooxanthren-1-ol
-
IC50: 0.03 mM
3-O-acetyl-11-keto-boswellic acid
-
0.03 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',6,7-trihydroxyisoflavan
-
-
4',6,7-trihydroxyisoflavanone
-
-
4',6,7-trihydroxyisoflavone
-
-
4'-chloro-7,8-dihydroxyisoflavone
-
-
4,15-dihydroxy-5,8,11,13-eicosatetraenoic acid
-
IC50: 0.0081 mM
4,4'-propane-2,2-diylbis(2,6-dibromophenol)
-
IC50: 0.01 mM
4-(2-oxapentadeca-4-yne) phenylpropanoic acid
-
-
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
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%
5,15-dihydroxy-5,8,11,13,17-eicosapentaenoic acid
-
IC50: 0.0008 mM
5,8,11,14-Eicosatetraynoic acid
-
0.001 mM, 77% inhibition
5,8,11,14-Eicosatetraynoic acid
-
0.01 mM, 86% inhibition
5,8,11,14-Eicosatetraynoic acid
-
IC50: 0.00006 mM
5,8,11,14-Eicosatetraynoic acid
-
-
5,8,11-eicosatriynoic acid
-
-
5-Hydroxydopamine
-
-
6,17-dihydroxy-4,7,10,13,15,19-eicosahexaenoic acid
-
IC50: 0.0004 mM
6,7-dihydroxy-3',4'-methylenedioxyisoflavan
-
-
6,7-dihydroxy-3',4'-methylenedioxyisoflavone
-
-
6,7-dihydroxy-3'-methylisoflavan
-
-
6,7-dihydroxy-3'-methylisoflavanone
-
-
6,7-dihydroxy-4'-methoxyisoflavan
-
-
6,7-dihydroxy-4'-methoxyisoflavanone
-
-
6,7-dihydroxy-4'-methoxyisoflavone
-
-
6,7-dihydroxy-4'-nitroisoflavone
-
-
6-Hydroxydopamine
-
-
7,8-dihydroxy-3',4'-dimethoxyisoflavan
-
-
7,8-dihydroxy-3'-methylisoflavone
-
-
7,8-dihydroxy-3'-trifluoromethylisoflavone
-
-
7,8-dihydroxy-4'-methoxyisoflavan
-
-
7,8-dihydroxy-4'-methylisoflavan
-
-
7,8-dihydroxy-4'-methylisoflavone
-
-
7,8-dihydroxyisoflavone
-
-
7-hydroxy-H-benzopyran-4-one derivatives
-
weak inhibition
8-hydroxyquinoline
-
1 mM, 35% inhibition
AA861
-
a 12-LOX inhibitor
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
alpha-mangostin
-
NSC30552, a natural product, caspase-3 pathway inhibitor, performs selective inhibition of 12-LO
arachidonic acid
-
substrate inhibition
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
-
-
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
baicalein
-
potent in vitro inhibitor of platelet 12-LOX
baicalein
-
inhibition of 12-LOX enzymatic activity using baicalein inhibits MMP9 expression in PC3 cells
baicalein
-
12-LOX inhibition attenuates platelet aggregation
benzoyl chloride
-
-
bestatin 7
-
IC50: 0.0023 mM
BW755C
-
0.01 mM, 13% inhibition
BW755C
-
0.01 mM, 72% inhibition
BWA137C
-
-
caffeic acid
-
0.01 mM, 20-30% inhibition
celecoxib
-
0.01 mM inhibits LOX-12 by 7%
chloroglyoxylic acid ethyl ester
-
-
chlorpromazine
-
-
cinnamyl 3,4-dihydroxy-cyanocinnamate
-
CDC
cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate
-
-
cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate
Q02759
-
Cu2+
-
-
dysidenin
-
-
EDTA
-
1 mM, 40% inhibition
eicosatetraynoic acid
-
0.01 mM, 90-95% inhibition
eicosatetraynoic acid
-
0.1 mM, complete inhibition
eicosatetraynoic acid
-
-
eicosatetraynoic acid
-
-
epinephrine
-
-
esculetin
-
0.01 mM, 90-95% inhibition
esculetin
-
0.01 mM, complete inhibition
esculetin
-
-
esculetine
-
inhibits the enzyme and its binding to cytoplasmic muscle fibrills, overview
fluphenazine
-
-
gossypol acetic acid
-
non-competitive with respect to arachidonate
GT-E
-
100 mM, dried radix of Glycine tomentella freeze-dried to a powder, IC50: 0.00072 mg/ml
-
H-benzopyran-4-one derivatives
-
weak inhibition
iodoacetate
-
1 mM, 5% inhibition
isonicotinaldehyde
-
-
Lubrol
-
0.2%, 60% inhibition
-
methyl-4-pyridyl ketone
-
-
N-(4-chlorophenyl)-N-hydroxy-N'-(3-chlorophenyl)urea
-
-
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-benzyl-N-hydroxy-5-phenylpentanamide
-
-
N-[(2,5-dichloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
-
-
N-[(4-chloro-1-hydroxynaphthalen-2-yl)(furan-2-yl)methyl]acetamide
-
-
N-[(5-bromo-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
-
-
N-[(5-bromo-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]propanamide
-
-
N-[(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
-
-
N-[(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
-
N-[(5-bromofuran-2-yl)(5-chloro-8-hydroxyquinolin-7-yl)methyl]propanamide
-
-
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)(4-fluorophenyl)methyl]propanamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]propanamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(5-methylthiophen-2-yl)methyl]propanamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(cyclopropyl)methyl]acetamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(cyclopropyl)methyl]propanamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]-4-methylbenzamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]benzamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]propanamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
-
N-[(5-chloro-8-hydroxyquinolin-7-yl)methyl]acetamide
-
-
N-[(5-chloro-8-methoxyquinolin-7-yl)(furan-2-yl)methyl]propanamide
-
-
N-[(5-fluoro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
-
-
N-[(5-fluoro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
-
-
N-[(8-hydroxy-5-nitroquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
-
N-[(8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
-
N-[(R)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
-
-
N-[(R)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
-
N-[(S)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
-
-
N-[(S)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
-
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)-2-methylpropyl]acetamide
-
-
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)-2-methylpropyl]propanamide
-
-
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)ethyl]acetamide
-
-
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)ethyl]propanamide
-
-
N-[1-(5-fluoro-8-hydroxyquinolin-7-yl)ethyl]acetamide
-
-
N-[furan-2-yl(8-hydroxy-5-nitroquinolin-7-yl)methyl]propanamide
-
-
NCTT-956
-
12-LOX inhibition attenuates platelet aggregation
NEM
-
1 mM, 15% inhibition
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
nicotinoyl chloride
-
-
nordihydroguaiaretic acid
-
0.01 mM, 90-95% inhibition
nordihydroguaiaretic acid
-
0.01 mM, 48% inhibition
nordihydroguaiaretic acid
-
0.01 mM, 97% inhibition
nordihydroguaiaretic acid
-
IC50: 0.0022 mM
nordihydroguaiaretic acid
-
-
nordihydroguaiaretic acid
-
0.04 mM, 65-75% inhibition
nordihydroguaiaretic acid
-
IC50: 0.0051 mM
nordihydroguaiaretic acid
-
100 mM, IC50: 0.0016 mg/ml
NSC172033
-
a synthetic compound from the NCI library
NSC292213
-
a synthetic compound from the NCI library
NSC617570
-
a synthetic compound from the NCI library
p-hydroxymercuribenzoate
-
1 mM, 75% inhibition
PD146176
-
-
PD146176
-
selective inhibitor of 12/15-LOX, macrophages treated with PD146176 elaborate reduced levels of interleukin-12 in response to Toxoplasma gondii antigen
picolinaldehyde
-
-
pyruvoyl chloride
-
-
quercetin
-
-
Renex
-
-
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
-
Sn2+
-
5 mM SnCl2, complete inhibition
Sn2+
-
3.7 mM, complete inhibition
Trifluoperazine
-
-
Triton X-100
-
-
Tween 20
-
-
Zn2+
-
3.7 mM, complete inhibition
michellamine B
-
NSC661755, potent but non-selective inhibitor, a natural anti-viral agent
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
-
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
-
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
13-hydroperoxy-octadecadienoic acid
-
-
2-arachidonoylglycerol
-
activates 12(S)-HETE production in vivo
alpha-Naphthol
Q02759
slight activation of enzyme activity at 0.25 mM, but not at 0.5 mM
ATP
-
2 mM ATP + 1 mM CaCl2 stimulate approximately 2fold
beta-boswellic acid
-
0.03 mM, in the absence of Ca2+
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
-
additional information
-
dihydroceramide has no effect
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0039
(Z,Z,Z,E)-5,8,11,13-eicosatetraenoic acid
-
-
0.0355
1-linoleoyl lysophosphatidic acid
-
pH 7.5, 25C
0.0151
1-linoleoyl lysophosphatidylcholine
-
pH 7.5, 25C
0.0045
5(S)-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid
-
-
0.003
5,8,11,14,17-eicosapentaenoic acid
-
-
0.024
5,8,11,14,17-eicosapentaenoic acid
-
-
0.03
5,8,11,14,17-eicosapentaenoic acid
-
-
0.0035
8,11,14-Eicosatrienoic acid
-
-
0.079
8,11,14-Eicosatrienoic acid
-
-
0.004
arachidonic acid
-
mutant enzyme M338L
0.005
arachidonic acid
-
-
0.0066
arachidonic acid
-
-
0.007
arachidonic acid
-
mutant enzyme M562L
0.0072
arachidonic acid
-
cytosolic hp-12LOX, pH 7.4, recombinant wild-type enzyme
0.008
arachidonic acid
-
-
0.0082
arachidonic acid
-
pH 7.4, 20C, wild-type
0.0087
arachidonic acid
-
membrane hp-12LOX, pH 7.4, recombinant wild-type enzyme
0.009
arachidonic acid
-
wild type enzyme
0.0109
arachidonic acid
-
pH 7.4, 20C, mutant R403L
0.015
arachidonic acid
-
-
0.018
arachidonic acid
-
mutant enzyme M367V
0.022
arachidonic acid
-
-
0.08
arachidonic acid
-
-
0.0125
linoleic acid
-
pH 7.4, 20, mutant Y98A
0.0169
linoleic acid
-
pH 7.4, 20, wild-type
0.0169
linoleic acid
-
pH 7.4, 20C, wild-type
0.0213
linoleic acid
-
pH 7.4, 20, mutant Y98F
0.0213
linoleic acid
-
pH 7.4, 20C, wild-type
0.0281
linoleic acid
-
pH 7.4, 20C, mutant R403L
0.03
linoleic acid
-
-
0.0312
linoleic acid
-
pH 7.5, 25C
0.0114
methyl arachidonate
-
pH 7.4, 20C, mutant R403L
0.0052
O2
-
pH 7.4, wild-type enzyme, with substrate linoleic acid
0.007
O2
-
pH 7.4, mutant L367W, with substrate linoleic acid
0.009
O2
-
pH 7.4, mutant L367E, with substrate linoleic acid; pH 7.4, mutant L367K, with substrate linoleic acid
0.0401
O2
-
pH 7.4, mutant L367F, with substrate linoleic acid
7
O2
-
-
0.018
methyl arachidonate
-
pH 7.4, 20C, wild-type
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
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.5
arachidonate
-
pH 7.5, 15C
3
arachidonate
-
mutant enzyme A416G
14
arachidonate
-
wild-type enzyme
17.8
arachidonate
-
pH 7.5, 30C
46
arachidonate
-
pH 7.5, 45C
1.4
arachidonic acid
-
at 15C, pH 7.5
7.2
arachidonic acid
-
mutant enzyme M561L
8.4
arachidonic acid
-
wild type enzyme and mutant enzyme M338L
18
arachidonic acid
-
mutant enzyme M367V
20
arachidonic acid
-
at 40C, pH 7.5
14.7
linoleic acid
-
pH 7.4, 20, mutant Y98A
44.2
linoleic acid
-
pH 7.4, 20, wild-type
47.23
linoleic acid
-
pH 7.4, 20C, wild-type
65.2
linoleic acid
-
pH 7.4, 20, mutant Y98F
0.3
O2
-
pH 7.4, mutant L367K, with substrate linoleic acid
2.2
O2
-
pH 7.4, mutant L367E, with substrate linoleic acid
4.4
O2
-
pH 7.4, mutant L367W, with substrate linoleic acid
5.6
O2
-
pH 7.4, mutant L367F, with substrate linoleic acid
13.1
O2
-
-
13.7
O2
-
pH 7.4, wild-type enzyme, with substrate linoleic acid
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.4
arachidonic acid
-
at 15C, pH 7.5
290
50
arachidonic acid
-
at 40C, pH 7.5
290
1410
arachidonic acid
-
pH 7.4, 20C, wild-type
290
1950
arachidonic acid
-
pH 7.4, 20C, mutant R403L
290
830
linoleic acid
-
pH 7.4, 20C, mutant R403L
428
1170
linoleic acid
-
pH 7.4, 20, mutant Y98A
428
2600
linoleic acid
-
pH 7.4, 20, wild-type
428
2650
linoleic acid
-
pH 7.4, 20C, wild-type
428
3060
linoleic acid
-
pH 7.4, 20, mutant Y98F
428
170
methyl arachidonate
-
pH 7.4, 20C, mutant R403L
136335
760
methyl arachidonate
-
pH 7.4, 20C, wild-type
136335
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0025
11-thialinoleic acid
-
-
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
0.017
neodysidenin
-
pH 8.0, recombinant enzyme
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0007
2,3,4,5-tetrabromo-6-(2,4-dibromophenoxy)phenol
-
IC50: 0.0007 mM
0.0041
2,3,4,5-tetrabromo-6-(4,5-dibromo-2-hydroxyphenoxy)phenol
-
IC50: 0.0041 mM
0.00041
2,3,5-tribromo-6-(4,5-dibromo-2-hydroxyphenoxy)phenol
-
IC50: 0.00041 mM
0.012
2,4-dibromo-6-(2,4-dibromo-6-methoxyphenoxy)phenol
-
IC50: 0.012 mM
0.007
2,6-dibromo-4-[1-(3-bromo-4-hydroxyphenyl)-1-methylethyl]phenol
-
IC50: 0.007 mM
0.00078
3'-chloro-7,8-dihydroxyisoflavone
-
pH 7.5, 22C
0.0075
3,15-dihydroxy-8,11,13-eicosatrienoic acid
-
IC50: 0.0075 mM
0.05
3,4,6,8-tetrabromooxanthren-1-ol
-
IC50: 0.05 mM
0.006
3,4,6-tribromo-2-(2,4-dibromophenoxy)phenol
-
IC50: 0.006 mM
0.047
3,4-dibromo-2-(5-bromo-2-hydroxyphenoxy)phenol
-
IC50: 0.047 mM
0.03
3,6,8-tribromooxanthren-1-ol
-
IC50: 0.03 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
-
IC50: 0.0004 mM
0.017
4',6,7-trihydroxyisoflavan
-
pH 7.5, 22C
0.0038
4',6,7-trihydroxyisoflavanone
-
pH 7.5, 22C
0.0087
4',6,7-trihydroxyisoflavone
-
pH 7.5, 22C
0.00048
4'-chloro-7,8-dihydroxyisoflavone
-
pH 7.5, 22C
0.0081
4,15-dihydroxy-5,8,11,13-eicosatetraenoic acid
-
IC50: 0.0081 mM
0.01
4,4'-propane-2,2-diylbis(2,6-dibromophenol)
-
IC50: 0.01 mM
0.0008
5,15-dihydroxy-5,8,11,13,17-eicosapentaenoic acid
-
IC50: 0.0008 mM
0.00006
5,8,11,14-Eicosatetraynoic acid
-
IC50: 0.00006 mM
0.0004
6,17-dihydroxy-4,7,10,13,15,19-eicosahexaenoic acid
-
IC50: 0.0004 mM
0.011
6,7-dihydroxy-3',4'-methylenedioxyisoflavan
-
pH 7.5, 22C
0.1
6,7-dihydroxy-3',4'-methylenedioxyisoflavone
-
above, pH 7.5, 22C
0.015
6,7-dihydroxy-3'-methylisoflavan
-
pH 7.5, 22C
0.014
6,7-dihydroxy-3'-methylisoflavanone
-
pH 7.5, 22C
0.0076
6,7-dihydroxy-4'-methoxyisoflavan
-
pH 7.5, 22C
0.0016
6,7-dihydroxy-4'-methoxyisoflavanone
-
pH 7.5, 22C
0.1
6,7-dihydroxy-4'-methoxyisoflavone
-
above, pH 7.5, 22C
0.0058
6,7-dihydroxy-4'-nitroisoflavone
-
pH 7.5, 22C
0.1
7,8-dihydroxy-3',4'-dimethoxyisoflavan
-
above, pH 7.5, 22C
0.0036
7,8-dihydroxy-3'-methylisoflavone
-
pH 7.5, 22C
0.00062
7,8-dihydroxy-3'-trifluoromethylisoflavone
-
pH 7.5, 22C
0.026
7,8-dihydroxy-4'-methoxyisoflavan
-
pH 7.5, 22C
0.07
7,8-dihydroxy-4'-methylisoflavan
-
pH 7.5, 22C
0.0016
7,8-dihydroxy-4'-methylisoflavone
-
pH 7.5, 22C
0.0064
7,8-dihydroxyisoflavone
-
pH 7.5, 22C
0.00058
alpha-mangostin
-
pH 8.0, recombinant enzyme
0.0023
bestatin 7
-
IC50: 0.0023 mM
0.009
dysidenin
-
above, pH 8.0, recombinant enzyme
0.0049
michellamine B
-
pH 8.0, recombinant enzyme
0.075
N-([5-chloro-2-(dimethylamino)-8-hydroxyquinolin-7-yl](furan-2-yl)methyl)acetamide
-
value above, pH 8.0, 23C
0.075
N-([5-chloro-8-hydroxy-2-(piperidin-1-yl)quinolin-7-yl](furan-2-yl)methyl)acetamide
-
value above, pH 8.0, 23C
0.075
N-[(2,5-dichloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
-
value above, pH 8.0, 23C
0.075
N-[(4-chloro-1-hydroxynaphthalen-2-yl)(furan-2-yl)methyl]acetamide
-
value above, pH 8.0, 23C
0.002
N-[(5-bromo-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
-
pH 8.0, 23C
0.002
N-[(5-bromo-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]propanamide
-
pH 8.0, 23C
0.001
N-[(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
-
pH 8.0, 23C
0.014
N-[(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
pH 8.0, 23C
0.075
N-[(5-bromofuran-2-yl)(5-chloro-8-hydroxyquinolin-7-yl)methyl]propanamide
-
value above, pH 8.0, 23C
0.003
N-[(5-chloro-8-hydroxy-1,2,3,4,4a,8a-hexahydroquinolin-7-yl)(furan-2-yl)methyl]propanamide
-
pH 8.0, 23C
0.05
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-fluorophenyl)methyl]propanamide
-
value above, pH 8.0, 23C
0.15
N-[(5-chloro-8-hydroxyquinolin-7-yl)(4-methylphenyl)methyl]propanamide
-
value above, pH 8.0, 23C
0.0035
N-[(5-chloro-8-hydroxyquinolin-7-yl)(5-methylthiophen-2-yl)methyl]propanamide
-
pH 8.0, 23C
0.003
N-[(5-chloro-8-hydroxyquinolin-7-yl)(cyclopropyl)methyl]acetamide
-
pH 8.0, 23C
0.0016
N-[(5-chloro-8-hydroxyquinolin-7-yl)(cyclopropyl)methyl]propanamide
-
pH 8.0, 23C
0.025
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]-4-methylbenzamide
-
value above, pH 8.0, 23C
0.003
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
-
pH 8.0, 23C
0.025
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]benzamide
-
value above, pH 8.0, 23C
0.001
N-[(5-chloro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]propanamide
-
pH 8.0, 23C
0.001
N-[(5-chloro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
-
pH 8.0, 23C
0.001
N-[(5-chloro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
pH 8.0, 23C
0.15
N-[(5-chloro-8-hydroxyquinolin-7-yl)methyl]acetamide
-
value above, pH 8.0, 23C
0.075
N-[(5-chloro-8-methoxyquinolin-7-yl)(furan-2-yl)methyl]propanamide
-
value above, pH 8.0, 23C
0.005
N-[(5-fluoro-8-hydroxyquinolin-7-yl)(furan-2-yl)methyl]acetamide
-
pH 8.0, 23C
0.002
N-[(5-fluoro-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
-
pH 8.0, 23C
0.0008
N-[(8-hydroxy-5-nitroquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
pH 8.0, 23C
0.0034
N-[(8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
pH 8.0, 23C
0.025
N-[(R)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
-
pH 8.0, 23C
0.025
N-[(R)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
pH 8.0, 23C
0.00043
N-[(S)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]acetamide
-
pH 8.0, 23C
0.00038
N-[(S)-(5-bromo-8-hydroxyquinolin-7-yl)(thiophen-2-yl)methyl]propanamide
-
pH 8.0, 23C
0.0026
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)-2-methylpropyl]acetamide
-
pH 8.0, 23C
0.0012
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)-2-methylpropyl]propanamide
-
pH 8.0, 23C
0.15
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)ethyl]acetamide
-
value above, pH 8.0, 23C
0.05
N-[1-(5-chloro-8-hydroxyquinolin-7-yl)ethyl]propanamide
-
value above, pH 8.0, 23C
0.075
N-[1-(5-fluoro-8-hydroxyquinolin-7-yl)ethyl]acetamide
-
value above, pH 8.0, 23C
0.0012
N-[furan-2-yl(8-hydroxy-5-nitroquinolin-7-yl)methyl]propanamide
-
pH 8.0, 23C
0.1
neodysidenin
-
above, pH 8.0, recombinant enzyme
0.0022
nordihydroguaiaretic acid
-
IC50: 0.0022 mM
0.0051
nordihydroguaiaretic acid
-
IC50: 0.0051 mM
0.00021
NSC172033
-
pH 8.0, recombinant enzyme
0.00015
NSC292213
-
pH 8.0, recombinant enzyme
0.00019
NSC617570
-
pH 8.0, recombinant enzyme
0.00044
quercetin
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0003
-
enzyme from platelet
0.0011
-
enzyme from leukocyte
0.0018
-
-
0.033
-
-
0.3
-
epithelial enzyme
0.7
-
leukocyte enzyme
1.7
-
-
8
-
purified enzyme
51.8
-
commercial preparation
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
-
almost inactive at pH 6 and pH 9
6.5 - 7
-
activity with arachidonate and linoleate
7 - 8
-
-
7
-
broad
7.3 - 7.9
-
-
7.4 - 8
-
-
7.5 - 8.5
-
-
7.5
P18054
assay at
7.5
-
assay at
7.5
O70582
assay at
8 - 8.2
Q70EX8
-
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
7.4 - 8.7
-
-
7.5 - 11
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10
-
cytosolic fraction
22
-
assay at
23
-
assay at
25 - 37
-
-
25
P18054
assay at
25
-
assay at
25
-
assay at
30
-
assay at
37
-
assay at
37
O70582
assay at
37
Q02759
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
epidermoid carcinoma cells
Manually annotated by BRENDA team
-
primary human aortic smooth muscle cells
Manually annotated by BRENDA team
-
the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the Alzheimers disease brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder
Manually annotated by BRENDA team
-
12/15-LOX is selectively enhanced in the periphery, 12/15-LOX-expressing myeloid cells are enriched in the brain during chronic toxoplasmosis
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
12/15-LOX is selectively enhanced in the periphery, 12/15-LOX-expressing myeloid cells are enriched in the brain during chronic toxoplasmosis
-
Manually annotated by BRENDA team
-
most tumors show constitutive overexpression of platelet-type mRNA, leukocyte-type specific transcripts are detectable only in a few tumors
Manually annotated by BRENDA team
-
12-LOX is overexpressed in a variety of human tumors
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
capillary endothelial cell line CD4
Manually annotated by BRENDA team
-
umbelical vein endothelial cells and foreskin dermal microvascular endothelial cells
Manually annotated by BRENDA team
-
platelet-type enzyme
Manually annotated by BRENDA team
-
12-LOX overexpression
Manually annotated by BRENDA team
-
macrophage cell line
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
macrophage cell line
-
Manually annotated by BRENDA team
-
platelet-type enzyme is the 12-lipoxygenase isoform responsible for the generation of most of the 12-hydroxyeicosateteaenoic acid
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
induced by a Ca2+ ionophore, from acute myeloid leukemic and acute lymphoid leukemic patients, upregulation of the enzyme, quantitative expression analysis
Manually annotated by BRENDA team
-
polymorphonuclear
Manually annotated by BRENDA team
-
from healthy individuals, quantitative expression analysis
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
enzyme activity is attributed predominantly to the neutrophils appearing in sinusoidal cavities rather than the non-parechymal cells
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
12/15-LOX is a macrophage-selective regulator of interleukin-12 production
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
P39654
macrophages that overexpress 12/15LO have reduced ATP-binding cassette G1 expression, increased transporter phosphorylation, and reduced cholesterol efflux
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
peritoneal, 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
-
Manually annotated by BRENDA team
-
primary cortical culture
Manually annotated by BRENDA team
-
expression is dependent on differentiation of the ovary
Manually annotated by BRENDA team
-
expression of platelet-type 12-LO, isozyme P-12-LO, and leukocyte-type 12-LO, isozyme L-12-LO
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
very high 12-lipoxygenase activity
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
vascular smooth muscle, the enzyme associates with alpha-actin fibers
Manually annotated by BRENDA team
-
umbilical artery, the enzyme associates with alpha-actin fibers
Manually annotated by BRENDA team
-
prostate stromal cells
Manually annotated by BRENDA team
additional information
Q02759
the leukocyte-type isozyme is widely distributed in cell types, while the epidermis-type and the platelet-type isozymes are more limited
Manually annotated by BRENDA team
additional information
-
expression of p12-LOX is significantly higher in JB6P+ cells than in JB6P- cells that are resistant to transformation
Manually annotated by BRENDA team
additional information
-
Plox-86 cells overexpress leukocyte-type 12/15-LO. Significant increase of monocyte chemoattractant protein-1 mRNA in Plox-86 cells
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
-
more than half of the activity
Manually annotated by BRENDA team
-
predominant in
Manually annotated by BRENDA team
-
platelet 12-lipoxygenase
Manually annotated by BRENDA team
-
membrane binding activities of wild-type platelet 12-lipoxygenase and mutant enzymes at pH 7.4, role of the PLAT domain membrane binding, overview
Manually annotated by BRENDA team
-
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
-
Manually annotated by BRENDA team
additional information
-
subcellular distribution analysis, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
77000
-
SDS-PAGE
671591
158000
-
about, recombinant His-tagged wild-type and mutant enzymes, gel filtration
688398
675000
-
about, recombinant no-PLAT-mutant, gel filtration
688398
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 72000, SDS-PAGE
?
-
x * 72000, SDS-PAGE
?
-
x * 75305, calculation of nucleotide sequence
?
-
x * 60000-80000, SDS-PAGE
dimer
-
2 * 76500, recombinant His-tagged enzyme, SDS-PAGE
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
oligomer
-
x * 62650, recombinant no-PLAT-mutant, SDS-PAGE
monomer
-
1 * 74700, dynamic light scattering
additional information
-
structural modeling, overview
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)
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0
-
loses appreciable activity when left overnight in an ice bath
395420
4
-
half-life: 24 h
395408
4
-
90% loss of activity after 4 h
395411
4
-
half-life: less than 1 h
395423
25
-
significant activity decrease above 25C
671591
37
-
rapid inactivation by the product hydroperoxy fatty acid, at low concentrations, 10-100 nM
395402
40
-
10 min, stable below
395417
45
-
10 min, 60% loss of activity
395417
50
-
10 min, 86% loss of activity
395417
50
-
3 min, enzyme solubilized with 1% deoxycholate, 20% loss of activity
395420
65
-
3 min, enzyme solubilized with 1% deoxycholate, complete loss of activity
395420
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the enzyme shows higher activity in 50 mM CAPS buffer (pH 10-11) and glycine buffer (pH 8.5-10.5) than in 50 mM Tris-HCl (pH 7-9)
-
severe autoinactivation is observed at high substrate concentrations if the substrate is not HPLC-purified and stored at -80C
-
15-25% loss of activity upon freezing and thawing
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, stable for at least 1 week
-
4C, half-life of leukocyte enzyme is 2 h, half-life of platelet enzyme is 70 h
-
-80C, 10% glycerol
-
-20C, remains stable for 6 weeks
-
-80C, 10-20% glycerol
-
-80C, 10% glycerol
-
4C, half-life: less than 1 h
-
-70C, 1 month, no appreciable loss of activity
-
-70C, 1 month
-
-70C, 20% glycerol, 10 mM 2-mercaptoethanol, 0.3% Triton X-305, enzyme retains complete activity after 1 month
-
-80C, stable for at least 4 months
-
4C, half-life: 24 h, markedly stabilized by 0.02 mM Fe2+
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
on Ni column
-
by one step Ni2+ affinity chromatography, more than 90% pure
-
recombinant His-tagged enzyme
-
recombinant His-tagged isozyme 12-hLO by nickel affinity chromatography
P18054
recombinant His-tagged wild-type and mutant enzymes from Spodoptera frugiperda Sf9 cells by nickel affinity chromatography
-
to greater than 90% purity
-
using Ni-NTA chromatography
-
on Ni column
-
using Ni-NTA chromatography
-
using Ni-NTA chromatography
-
by anion exchange chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ligated into the pQE-9 plasmid and expressed as N-terminal His-tag fusion protein in Escherichia coli (XL-1 Blue)
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expressed with hexa-His tags
-
expression in CHO and in neuro-2 A neuroblastoma cells both stably expressing human APP carrying the K670N/M671L Swedish mutation, expression analysis
-
expression in Escherichia coli
-
expression of His-tagged enzyme
-
expression of His-tagged wild-type and mutant enzymes in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system
-
expression of isozyme 12-hLO as His-tagged enzyme
P18054
expression of N-terminally His6-tagged enzyme
-
gene ALOX15, DNA and amino acid sequence determination and analysis of wild-type and mutant T560M, promoter sequence analysis, genotyping, overview, expression of wild-type and mutant enzymes in Escherichia coli and HEK-297 cells, the mutant shows a low expression level in both systems compared to the wild-type enzyme
-
overexpressed as N-terminally, His6-tagged protein
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expression in HEK 293 cells
-
expression in HEK-293 cells by using the eukaryotic expression vector pcDNA3
-
full-length cDNA for 12/15LO subcloned into vector pACCMVpLpA. Bone marrow-derived macrophages infected at a multiplicity of infection of 50 for 48 h with recombinant adenoviral vector AdLO to overexpress 12/15LO
P39654
genotyping, overexpression of His-tagged mutant W633X and wild-type Alox12b proteins in COS7 cells
O70582
ligated into the pQE-9 plasmid and expressed as N-terminal His-tag fusion protein in Escherichia coli (XL-1 Blue)
-
rat beta INS-1 cells are transduced with adeno-associated virus vector ACSM12-LO, that encodes mouse leukocyte type 12-lipoxygenase
-
transgenic mice overexpressing 12/15-LOX in cardiomyocytes
-
two cDNA clones encoding the platelet-type and the leukocyte-type isoforms expressed in COS-7 cells
-
expressed in Escherichia coli
-
expressed in Escherichia coli and Sf9 insect cells
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expression in Escherichia coli
Q70EX8
gene alox15, expression analysis and genotyping of wild-type and iron-deficient mutant rats, gene alox15 doesnot respond to iron, transcription regulation via cytokines and growth factors, overview
Q02759
12/15LO stably overexpressed in mouse J774 macrophages
-
enzyme is cloned into the expression vectors pSE280, pSE380, and pSE420. PSE380 yields the highest level of 12-lipoxygenase activity, expression in Escherichia coli Top10 cells
-
expressed from pET-20b(+) plasmid in Escherichia coli Rosetta 2 (DE3) cells
-
expressed in Escherichia coli
-
expression in insect cells using a baculovirus expression vector, expression as an N-terminal fusion protein with a 31-amino acid polypeptide carrying a six-histidine tag and an enterokinase cleavage site
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
level of 12-LOX expression is dose-dependently decreased by UVB and UVA-irradiation. Successful psoralen plus ultraviolet A, UVA-photochemotherapy-mediated inhibition of cell growth and inflammation via decreased 12-LOX expression. 15(S)-hydroxyeicosatetraenoic acid, 15-HETrE and 13(S)-hydroxyoctadecadienoic acid (15-LOX metabolites) significantly inhibit insulin-like growth factor II-induced 12-LOX expression
-
expression of ALOX12 remains on the same level during differentiation from monocyte to macrophage
-
insulin-like growth factor II induces 12-LOX expression and blocks cell cycle progression
-
an increase of ALOX15B expression during the differentiation of monocytes to macrophages is shown. Stimulation of macrophages with a set of cytokines and with hypoxia reveals that IL-4, IL-13, LPS and hypoxia further increase the ALOX15B mRNA
-
reduced monocyte chemoattractant protein-1 expression in mouse peritoneal macrophages from 12/15-LO null mice
-
siRNA decreases 12-LOX protein expression and hydroxyl radical signals occur in a 12-LOX small interfering RNA knockdown protein group compared with the baicalein control
-
12/15-LOX activity is enhanced during chronic, but not acute, toxoplasmosis
-
12/15-LOX is markedly upregulated in heart failure, cardiac expression is upregulated during pressure overload
-
strong expression of 12/15-LO in inflammatory synovial tissue
-
tumor necrosis factor-alpha induces p12-LOX in the early stage of tumorigenesis, induces p12-LOX expression both in JB6P+ and JB6P- cells
-
reduced monocyte chemoattractant protein-1 expression in mouse peritoneal macrophages from 12/15-LO null mice
Mus musculus C57BL/6
-
-
12/15-LOX activity is enhanced during chronic, but not acute, toxoplasmosis
Mus musculus C57BL/6
-
-
ceramide increases mRNA and protein expression, and activity of 12-LOX
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C7S
-
site-directed mutagenesis, the mutant shows highly reduced iron content compared to the wild-type enzyme, but exchange of the surface-exposed cysteine alters neither the catalytic activity nor the reaction specificity
G441A
-
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, wild-type enzyme converts arachidonate only to (12R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid
G441S
-
the mutant enzyme G441A converts arachidonic acid to 8S-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid (major product) and (12R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid (minor product), wild-type enzyme converts arachidonate only to (12R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid
G441T
-
inactive mutant enzyme
Q294L
-
relative catalytic activity: 16.1% compared to wild-type 100%
T560M
-
naturally occurring enzyme mutant, the mutant shows 20fold reduced catalytic activity, genotyping using 12974 samples, the haplotypes show increased risk of coronary artery disease compared to non-carriers, overview
Q303L
-
mutant shows strongly impared catalytic activity, relative catalytic activity: 3.2% compared to wild-type 100%
T570M
-
mutant shows strongly impared catalytic activity, relative catalytic activity: 8.2% compared to wild-type 100%
W633X
O70582
naturally occurring mummy mutation, that introduces a nonsense codon into the C-terminal LOX catalytic domain, which results in truncation of the protein by 68 amino acids, mummy is identified in an ethylnitrosurea mutagenesis screen for autosomal recessive developmental phenotypes, the mutant is catalytically inactive, Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
A455I
-
10% activity of the wild type enzyme
A455W
-
45% activity of the wild type enzyme
F390A
-
50% activity of the wild type enzyme
F390W
-
2% activity of the wild type enzyme
L183E/L192E
-
introduction of negatively charged residues at the intermonomer interface disturbs the hydrophobic dimer interaction of the wild-type LOX. Double mutant does not follow Michaelis-Menten kinetics. Double mutant are gradually inactivated at increasing substrate concentration
L367E
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, L367 is involved in oxygen access, overview
L367F
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, in silico mutagenesis and structural modeling, L367 is involved in oxygen access, overview
L367K
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, L367 is involved in oxygen access, overview
L367W
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site-directed mutagenesis, site-directed mutagenesis, the mutant shows reduced activity with O2 compared to the wild-type enzyme, L367 is involved in oxygen access, overview
R403L
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a loss of electrostatic interaction between Arg403 and negatively charged amino acid residues of alpha2-helix has only minor impact on protein folding, but partially destabilizes the tertiary structure of the enzyme. Arg403Leu exchange induces strong substrate inhibition. kcat/Km values strongly decreased for linoleic acid and methyl arachidonate but almost unchanged for arachidonic acid compared to wild-type
V631A
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150% increase of activity of the wild type enzyme
V631F
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4% activity of the wild type enzyme
V631G
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173% increase of activity of the wild type enzyme
W181E/H585E
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introduction of negatively charged residues at the intermonomer interface disturbs the hydrophobic dimer interaction of the wild-type LOX. Double mutant does not follow Michaelis-Menten kinetics. Double mutant are gradually inactivated at increasing substrate concentration
Y98A
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kcat and Km (linoleic acid) decreased compared to wild-type, mutant shows strongly reduced catalytic activity compared to wild-type
Y98F
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kcat and Km (linoleic acid) increased compared to wild-type
M338L
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Km-value for arachidonic acid is about 1/2 that of the wild type enzyme
M367V
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Km-value for arachidonic acid and turnover number are approximately double that of the wild-type enzyme
M562L
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Km-value for arachidonic acid is 77% of that of the wild type enzyme, turnover number is 85% of that of the wild type
G441V
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inactive mutant enzyme
additional information
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truncation of the N-terminal PLAT domain impairs catalytic activity but does not alter reaction specificity
T560M
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mutant shows impaired catalytic activity, relative catalytic activity: 25% compared to wild-type 100%
additional information
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12/15-LO knockout mice show reduced monocyte chemoattractant protein MCP-1 expression
W633X
Mus musculus A/J
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naturally occurring mummy mutation, that introduces a nonsense codon into the C-terminal LOX catalytic domain, which results in truncation of the protein by 68 amino acids, mummy is identified in an ethylnitrosurea mutagenesis screen for autosomal recessive developmental phenotypes, the mutant is catalytically inactive, Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
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additional information
Mus musculus C57BL/6
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12/15-LO knockout mice show reduced monocyte chemoattractant protein MCP-1 expression
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Y98R
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mutant shows strongly reduced catalytic activity compared to wild-type, mutant does not follow Michaelis-Menten-kinetics. Mutant is strongly inhibited by linoleic acid at concentrations above 0.01 mM
additional information
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 Belgrade rats, the lipids are almoste absent in wild-type rats, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the Alzheimers disease brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder. Thus, drugs that specifically reduce or block the 12/15-LOX metabolic pathway activation may warrant consideration as potential therapeutic interventions for Alzheimers disease
medicine
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psoralen plus ultraviolet A decreases 12-LOX expression, thus this UVA photochemotherapy is considered to be first-line treatment for patients with moderate to severe psoriasis. Interruption of 12-LOX catalytic activity and the 12-hydroxyeicosatetraenoic acid signaling pathway by increasing 15-LOX metabolites may be a promising target for psoriasis therapies
drug development
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cardiac 12/15-LOX is involved in the development of heart failure and inhibition of 12/15-LOX may be a novel treatment for this condition
drug development
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inhibition of 12/15-LOX provides robust protection against cell death preventing mitochondrial damage in oxidative stress-related brain injury
drug development
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p12-LOX pathway may be an effective target of chemoprevention for skin carcinogenesis
medicine
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prevention of increased 12-LO expression or activity in pancreatic beta cells could be a new way to prevent inflammation and damage to beta cells
drug development
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induction of pro-carcinogenic 12-LOX pathway by an anticancer ceramide, which may be relevant to cancer biologists studying drug resistant tumors and devising potent anticancer therapeutic strategies to treat drug resistant tumors. Induction of 12-LOX pathway by ceramide may have implications in understanding pathophysiology of neurodegenerative diseases involving reactive oxygen species generation and inflammation