ALOX12
Description
The ALOX12 (arachidonate 12-lipoxygenase, 12S type) is a protein-coding gene located on chromosome 17.
ALOX12 (EC 1.13.11.31), also known as arachidonate 12-lipoxygenase, 12-lipoxygenase, 12S-Lipoxygenase, 12-LOX, and 12S-LOX is a lipoxygenase-type enzyme that in humans is encoded by the ALOX12 gene which is located along with other lipoyxgenases on chromosome 17p13.3. ALOX12 is 75 kilodalton protein composed of 663 amino acids.
== Nomenclature ==
Other systematic names for ALOX12 include 12S-Lipoxygenase, platelet-type 12-lipoxygenase, arachidonate:oxygen 12-oxidoreductase, Delta12-lipoxygenase, 12Delta-lipoxygenase, and C-12 lipoxygenase. ALOX12, often termed plate platelet-type 12-lipoxygenase, is distinguished from leukocyte-type 12-lipoxygenase which is found in mice, rats, cows, and pigs but not humans. Leukocyte-type 12-lipoxygenase in these animal species shares 73-86% amino acid identity with human ALOX15 but only 57-66% identity with human platelet-type 12-lipoxygenase and, like ALOX15, metabolizes arachidonic acid primarily to 15(S)-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid (i.e. 15(S)-HpETE; see 15-Hydroxyeicosatetraenoic acid). Accordingly, rodent leukocyte 12-lipoxygenase is deemed an ortholog of ALOX15 and is designated as Alox15. Human ALOX12 and ALOX15 along with rodent leukocyte-type Alox12 and Alox15 are commonly termed 12/15-lipoxygenases based on their ability to metabolize arachidonic acid to both 12(S)-HpETE and 15(S)-HpETE and to conduct this same metabolism on arachidonic acid that is esterified to membrane phospholipids; human ALOX15B makes 15(S)-HpETE but not 12(S)-HpETE and therefore is not regarded as a 12/15-lipoxygenase. Studies on the role of ALOX12 in pathophysiology using the main models for such functional studies, rats and mice, are complicated because neither species possesses a lipoxygenase that makes a predominance of 12(S)-HETE and therefore is metabolically equivalent to ALOX12. For example, the functions inferred for Alox12 in mice made deficient in Alox12 using knockout methods may not indicate a similar function for ALOX12 in humans due to differences in these two enzymes' metabolic activities.
ALOX12 is a key enzyme involved in the metabolism of polyunsaturated fatty acids, specifically arachidonic acid and docosahexaenoic acid (DHA). It catalyzes the addition of molecular oxygen to these fatty acids, both in their free and esterified forms, resulting in the production of lipid hydroperoxides. These hydroperoxides can then be further reduced to their corresponding hydroxy species. ALOX12 is primarily known for converting arachidonic acid into (12S)-hydroperoxyeicosatetraenoate ((12S)-HPETE), a bioactive lipid involved in various biological processes, including platelet activation. ALOX12 can also participate in the epoxidation of double bonds in polyunsaturated fatty acids like DHA, leading to the formation of (13S,14S)-epoxy-DHA. Additionally, ALOX12 plays a role in the synthesis of specialized pro-resolving mediators (SPMs) like resolvin D5, which have anti-inflammatory and anti-aggregation properties. ALOX12 can also transform leukotriene A4 (LTA4) into the bioactive lipids lipoxin A4 (LXA4) and lipoxin B4 (LXB4), both of which have vasoactive properties. Furthermore, ALOX12 can peroxidize linoleate to (13S)-hydroperoxyoctadecadienoate (13S-HPODE). ALOX12 has been implicated in the regulation of vascular endothelial growth factor (VEGF) and integrin beta-1 expression, suggesting a potential role in tumorigenesis. ALOX12 is important for cell survival, potentially playing a role in both proliferation and the prevention of apoptosis in vascular smooth muscle cells. {ECO:0000250|UniProtKB:P39655, ECO:0000269|PubMed:16638750, ECO:0000269|PubMed:17493578, ECO:0000269|PubMed:18311922, ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:22237009, ECO:0000269|PubMed:22984144, ECO:0000269|PubMed:23504711, ECO:0000269|PubMed:23578768, ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:32404334, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693, ECO:0000269|PubMed:8500694, ECO:0000269|PubMed:9751607}
ALOX12 is also known as 12-LOX, 12S-LOX, LOG12.
