Cloned (Comment) | Organism |
---|---|
gene ALOX15, located on the short arm of chromosome 11 | Mus musculus |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | a non-heme iron in the active side | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
arachidonate + O2 | Mus musculus | - |
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate | - |
? | |
additional information | Mus musculus | 12/15-LOX generates (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate and (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate, when arachidonic acid is the substrate, the enzyme produces small amounts of 15S-HETE and primarily 12S-HETE (ratio of 1:3). In case of linolenic acid as a substrate, 13S-hydroxyoctadecadienoic acid (13S-HODE) is generated via the interstage product 13S-hydroperoxyoctadecadienoic acid (13SHPODE). Inflammatory eicosanoids are produced by eosinophils in a 12/15-LOX dependent manner. Another family of 12/15-LOX products are hepoxilins. They are enzymatic products of the conversion of 12S-HPETE, but can also be produced by non-enzymatic modification of 12S-HPETE or 12RHPETE. In the latter case, hemine or haemoglobin may act as a non-specific catalyst | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | P39654 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
aortic smooth muscle cell | - |
Mus musculus | - |
dendritic cell | immature | Mus musculus | - |
eosinophil | - |
Mus musculus | - |
epithelial cell | - |
Mus musculus | - |
kidney | - |
Mus musculus | - |
macrophage | resident peritoneal | Mus musculus | - |
additional information | not in peripheral monocytes | Mus musculus | - |
pancreatic islet | - |
Mus musculus | - |
respiratory system | - |
Mus musculus | - |
reticulocyte | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
arachidonate + O2 | - |
Mus musculus | (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate | - |
? | |
additional information | 12/15-LOX generates (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate and (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate, when arachidonic acid is the substrate, the enzyme produces small amounts of 15S-HETE and primarily 12S-HETE (ratio of 1:3). In case of linolenic acid as a substrate, 13S-hydroxyoctadecadienoic acid (13S-HODE) is generated via the interstage product 13S-hydroperoxyoctadecadienoic acid (13SHPODE). Inflammatory eicosanoids are produced by eosinophils in a 12/15-LOX dependent manner. Another family of 12/15-LOX products are hepoxilins. They are enzymatic products of the conversion of 12S-HPETE, but can also be produced by non-enzymatic modification of 12S-HPETE or 12RHPETE. In the latter case, hemine or haemoglobin may act as a non-specific catalyst | Mus musculus | ? | - |
? | |
additional information | the enzymatic peroxidation reaction consists of four consecutive steps: At first a hydrogen atom is stereoselectively abstracted from one of the bisallylic methylene-groups forming an enzyme-bound radical. Secondly one of the two associated cis-double bonds is rearranged and forms a conjugated cis-trans-diene. Consecutively a peroxy radical is produced by inserting molecular oxygen. Finally the radical is reduced by antarafacial re-inserting of a hydrogen atom. The resulting product of this peroxidation reaction depends on the respective fatty acid, which is used as a substrate | Mus musculus | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | lipoxygenases are composed of a N-terminal beta-barrel domain and a larger C-terminal catalytic domain harboring a non-heme iron in its active side | Mus musculus |
Synonyms | Comment | Organism |
---|---|---|
12/15-lipoxygenase | - |
Mus musculus |
12/15-LOX | - |
Mus musculus |
Alox15 | - |
Mus musculus |
Organism | Comment | Expression |
---|---|---|
Mus musculus | 12/15-LOX mRNA expression in cultured aortic smooth muscle cells is upregulated by angiotensin II, ATII. ATII also stimulates production of LOX-derived HETEs in arterial vessels and the kidney | up |
General Information | Comment | Organism |
---|---|---|
evolution | gene ALOX15 encodes for human 15-LOX type 1 and murine 12/15-LOX. Although the encoded enzymes display slightly different specificities (15- versus 12-lipoxygenating activity), these proteins represent evolutionary and functionally closely-related enzymes that share a high degree of sequence similarity. Of note, these 12/15LOXs that are encoded by the ALOX15 genes have separated from other LOXs early during evolution, although they share close biochemical properties with other LOXs such as ALOX12 or ALOX15B | Mus musculus |
physiological function | 12/15-LOX is implicated in the pathogenesis of multiple chronic inflammatory diseases, and its physiologic functions seem to include potent immune modulatory properties that physiologically contribute to the resolution of inflammation and the clearance of inflammation-associated tissue damage. 12/15-LOXs are also involved in the synthesis of lipoxins, which likewise act as anti-inflammatory, pro-resolving mediators. Inflammatory eicosanoids are produced by eosinophils in a 12/15-LOX dependent manner. Docosahexaenoic acid (DHA) is a further substrate of 12/15-LOX. The oxidation of DHA leads to the production of 17S-hydroxy-DHA, an anti-inflammatory mediator, which can be further metabolized into highly active and potent anti-inflammatory resolvins and protectins. 12/15-LOX can metabolize not only free PUFAs, but also PUFAs esterified to membrane-bound phospholipids as well as PUFAs within cholesterol esters. 12/15-LOX-derived mediators as regulators of inflammation, role of 12/15-LOX during inflammation, detailed overview. 12/15-LOX activity in resident macrophages interferes with theMFG-E8-dependent uptake of apoptotic cells (ACs) by inflammatory, immune-competent phagocytes and thereby fosters the non-immunogenic clearance of ACs, whereas 12/15-LOX-derived lipoxins directly increase the non-inflammatory uptake of dying cells. Possible role of 12/15-LOX in atherosclerosis | Mus musculus |