5Lipoxygenase

5-Lipoxygenase (5-LOX) is a non-heme iron–containing enzyme encoded by the ALOX5 gene in humans. It is a key enzyme in the lipoxygenase pathway of arachidonic acid metabolism, converting free arachidonic acid into leukotrienes in leukocytes and other inflammatory cells. 5-LOX activity requires the 5-LOX-activating protein (FLAP) for efficient conversion of arachidonic acid to 5-HPETE and subsequent formation of leukotriene A4 (LTA4). LTA4 can be hydrolyzed to leukotriene B4 (LTB4) or conjugated with glutathione to form LTC4, which is further converted to LTD4 and LTE4. The enzyme is cytosolic and contains non-heme iron; it is regulated by calcium, calmodulin, and membrane localization via FLAP.

Role in physiology and disease: 5-LOX–derived leukotrienes are potent mediators of inflammation and allergic responses. LTB4 acts as a neutrophil chemoattractant, while cysteinyl leukotrienes (LTC4, LTD4, LTE4) mediate bronchoconstriction and vascular permeability, contributing to asthma and allergic rhinitis, among other inflammatory conditions.

Clinical relevance: Given its central role in leukotriene synthesis, 5-LOX is a target for anti-inflammatory therapy. Zileuton is a 5-LOX inhibitor approved for asthma management; other 5-LOX inhibitors and dual inhibitors are under investigation. Genetic variations in ALOX5 can affect leukotriene production and disease susceptibility.

Genetics and biology: The ALOX5 gene is located on chromosome 10 in humans. The enzyme is highly expressed in leukocytes and mast cells, with activity modulated by cellular signals and FLAP-assisted localization.