12dioxygenase

12-dioxygenase is a term used in biochemistry to describe dioxygenase enzymes that insert both atoms of molecular oxygen into a substrate at the 12-position. In practice, the designation most often refers to enzymes in the lipoxygenase family, commonly called 12-lipoxygenases (12-LOX). These non-heme iron–containing enzymes act on polyunsaturated fatty acids such as arachidonic acid to produce a 12-hydroperoxide product, 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which is typically reduced to 12-hydroxy derivatives (12-HETE) by cellular reductases.

12-LOX activity has been described in various organisms, including mammals and plants. In mammals, platelet and leukocyte isoforms contribute to the generation of 12-HPETE/12-HETE, metabolites that participate in inflammatory signaling, hemostasis, and pathologies such as atherosclerosis. In plants, analogous dioxygenases contribute to oxylipin signaling and defense responses.

Biochemically, these enzymes are classified as oxygenases that catalyze regioselective insertion of oxygen into fatty acids, requiring iron at the active site. Substrate specificity and product profiles vary by organism and isoform, with some enzymes producing 12-HPETE, others favoring different oxygenation positions.

Terminology notes: 12-dioxygenase is not a universally standardized name; in many contexts it overlaps with 12-LOX terminology. Because different enzymes may exhibit 12-selective oxygenation, the precise activity should be described in terms of substrate, product, and organism.

Research on 12-dioxygenases informs understanding of lipid signaling, inflammation, and plant defense, and continues to be developed through lipidomics and structural biochemistry.