Lipoxygenases

Lipoxygenases are a family of non-heme iron-containing enzymes that catalyze the stereo- and regioselective incorporation of molecular oxygen into polyunsaturated fatty acids. The typical substrates are linoleic acid, linolenic acid, and arachidonic acid, yielding fatty acid hydroperoxides such as HPETEs in plants or animals, depending on the enzyme. LOX activity is characterized by distinct positional specificities (for example, 5-LOX, 8-LOX, 12-LOX, 15-LOX).

LOX enzymes are widespread in plants, animals, and microorganisms, but are especially studied in plants and vertebrates. In animals, LOX products include leukotrienes and hydroxyeicosatetraenoic acids that modulate inflammation, immunity, and vascular tone; 5-LOX participates in generating leukotrienes. In plants, LOX products function as oxylipins involved in defense responses, wound signaling, and the biosynthesis of jasmonates, which regulate growth and defense.

Chemically, LOX enzymes contain an iron center that cycles between Fe(II) and Fe(III) during catalysis. A hydrogen is abstracted from the fatty acid, and molecular oxygen is added to form a fatty acid hydroperoxide. The reaction is highly regio- and stereo-specific. In mammals, LOX activities are often associated with membrane lipids and may require accessory proteins; in the 5-LOX–FLAP system, FLAP assists substrate delivery.

Clinical and industrial relevance: LOX pathways are targets of anti-inflammatory therapy; zileuton inhibits 5-LOX and is used for asthma. LOX inhibitors and natural products are studied for inflammatory and allergic diseases. In food science, plant LOX activity can affect flavor and quality of oils and grains, sometimes causing off-flavors, while controlled LOX activity is used to generate aroma compounds in some fermented foods.

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