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.
The function of ALOX12 is further clouded by human ALOX15 which metabolizes arachidonic acid primarily to 15(S)-HpETE but also makes lesser but still significant amounts of 12(S)-HpETE (see ALOX15).
[13] The control of ALOX12 activity appears to rest principally on the availability of its polyunsaturated fatty acid (PUFA) substrates which are released from storage in membrane phospholipids by cell stimulation.
Far more commonly, however, 12S-HpETE is rapidly reduced to its hydroxyl product by ubiquitous cellular peroxidase activities thereby forming 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid, i.e. 12-hydroxyeicosatetraenoic acid or 12S-HETE:[19] 12S-HETE promotes inflammation responses, may be involved in the perception of puritis (i.e. itching) in the skin, and regulates regional blood flow in animal models; it also promotes the malignant behavior of cultured human cancer cells as well as the growth of certain cancers in animal models (see 12-HETE).
[22] Studies on rodents lacking or made deficient in the leukocyte-type 12-lipoxygenase, Alox12 (which is most closely related to human ALOX15) implicate this enzyme in: a) preventing the development and complications of dietary-induced and/or genetically induced diabetes, adipose cell/tissue dysfunction, and obesity; b) the development of atherosclerosis and Steatohepatitis; b) regulating blood vessel contraction, dilation, pressure, remodeling, and angiogenesis; c) maintaining normal renal, neurological, and brain function; and d) the development of Alzheimer's disease.
Indeed, in one study a Single-nucleotide polymorphism, rs2073438,[24] located in an intron region of the ALOX12 gene was significantly associated with total and percentage fat mass of obese compared to non-obese young Chinese men.
12(S)-HETE also dilates human coronary microcirculation arteries by activating these vessels' smooth muscle BKca Potassium channels and is therefore suggested to be an Endothelium-derived hyperpolarizing factor.
[9][25] Patients with Alzheimer's disease or other forms of dementia have significantly higher levels of 12(S)-HETE (and 15(S)-HETE) in cerebrospinal fluid compared to aged-matched normal individuals.
[19] Recently, hypermethylation of the ALOX12 gene in prostate cancer tissue was associated with clinical predictors for a high rate of recurrent disease.