Arachidonate 12-lipoxygenase (12-LOX)

Arachidonate 12-lipoxygenase (ALOX12), commonly referred to as **12-lipoxygenase** or **12S-lipoxygenase**, is an iron-containing enzyme encoded by the *ALOX12* gene on human chromosome 17p13.3.[2] It catalyzes the regioselective incorporation of molecular oxygen into polyunsaturated fatty acids such as arachidonic acid to produce bioactive lipid hydroperoxides—primarily **12(S)-hydroperoxy-eicosatetraenoic acid** [5]. These products can be further metabolized into various signaling molecules involved in inflammation, platelet aggregation, vascular tone regulation, adipose tissue biology, metabolic homeostasis, and neurological processes.[1][2][4][6] The enzyme plays a significant role in both physiological processes like hemostasis/platelet function as well as pathophysiological conditions including diabetes complications, atherosclerosis development/progression,[2] obesity-related disorders,[2] steatohepatitis,[2] neurodegeneration,[2], and general tissue inflammation.[6] Structural studies reveal that it contains a non-heme iron at its active site essential for catalysis; mutations affecting key histidine residues abolish enzymatic activity.[3]

Other names

12-lipoxygenase12S-Lipoxygenase12S-LOXALOX12[2]Platelet-type lipoxygenase (in some contexts)

Drugs or inhibitors targeting this enzyme typically act by blocking its catalytic activity—preventing the oxygenation of arachidonic acid to form pro-inflammatory lipid mediators such as hydroperoxyeicosatetraenoic acids (HETEs) and hepoxilins, thereby modulating inflammatory responses and platelet activation.[4][6]