12dioxygenases

12-dioxygenases are enzymes that catalyze the incorporation of molecular oxygen into substrates at the 12-position. In biochemistry and pharmacology, the term most often refers to 12-lipoxygenases (12-LOX), a subset of the lipoxygenase family that acts on polyunsaturated fatty acids such as arachidonic acid. These enzymes insert two oxygen atoms into the fatty acid, forming 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which is subsequently reduced to 12-hydroxyeicosatetraenoic acid (12-HETE) or rearranged into other oxylipins.

12-LOX enzymes are non-heme iron-dependent dioxygenases. They typically bind substrate in a hydrophobic pocket and use a catalytic iron to activate O2 for insertion. Isoforms exist in vertebrates and plants, including human 12S-LOX (ALOX12), human 12R-LOX (ALOX12B), and related enzymes in other species. These isoforms may have distinct tissue distributions and product profiles, contributing to inflammatory signaling, platelet function, epidermal barrier formation, and defense responses in plants.

Biological roles: 12-LOX products act as signaling mediators in inflammation, vascular function, and wound healing; in plants, 12-LOX–derived oxylipins participate in defense signaling and development.

Regulation and clinical relevance: activity is regulated at the level of expression and post-translational modifications, and dysregulation has been linked to inflammatory diseases and cancer. Inhibitors of 12-LOX are used in research to probe inflammatory and metabolic pathways.

See also lipoxygenases, oxylipins, arachidonic acid metabolism, non-heme iron enzymes.