5LOX

5-Lipoxygenase (5-LOX) is a member of the lipoxygenase family of non-heme iron–containing enzymes that catalyze the first committed step in the biosynthesis of leukotrienes from arachidonic acid. The enzyme is encoded by the ALOX5 gene and is primarily expressed in leukocytes such as neutrophils, eosinophils, and monocytes, as well as in other immune cells. Activation occurs in response to cellular calcium signals and requires the 5-LOX-activating protein (FLAP) to assemble a functional complex on the nuclear or endoplasmic reticulum membranes.

In the catalytic cycle, 5-LOX converts arachidonic acid to 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which is further converted to leukotriene A4 (LTA4). LTA4 is unstable and can be processed by LTA4 hydrolase to leukotriene B4 (LTB4), a neutrophil chemoattractant, or conjugated with glutathione to form LTC4, which is subsequently converted to LTD4 and LTE4, collectively known as cysteinyl leukotrienes.

These leukotrienes play roles in inflammation, including recruitment of leukocytes, promotion of bronchoconstriction, and increased vascular permeability. 5-LOX can participate in transcellular biosynthesis of additional lipid mediators through interactions with other cells and enzymes in the leukotriene pathway.

Clinical relevance and inhibition: Inhibitors of 5-LOX, such as zileuton, reduce leukotriene synthesis and are used in the treatment of asthma and certain inflammatory conditions. Other therapeutic approaches target FLAP or downstream leukotriene receptors and enzymes. Regulation of 5-LOX activity occurs at transcriptional and post-translational levels, influencing inflammatory responses.