Lipoxygenase
Lipoxygenase (LOX) is an enzyme that catalyzes the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4-pentadiene structure. Lipoxygenases are non-heme iron-containing enzymes that are widely distributed in plants, animals, and fungi. They play a crucial role in the metabolism of fatty acids, leading to the formation of various bioactive lipid mediators.
Structure
Lipoxygenases are typically composed of a single polypeptide chain and contain a non-heme iron atom at their active site. The iron atom is coordinated by three histidine residues and one asparagine residue. The enzyme's structure allows it to bind to its fatty acid substrate and facilitate the addition of molecular oxygen.
Function
Lipoxygenases are involved in the metabolism of arachidonic acid, linoleic acid, and other polyunsaturated fatty acids. They catalyze the formation of hydroperoxides, which are then converted into various signaling molecules, including leukotrienes, lipoxins, and hepoxilins. These lipid mediators are involved in a wide range of biological processes, including inflammation, immune response, and cell proliferation.
Types of Lipoxygenases
There are several types of lipoxygenases, classified based on the position at which they insert oxygen into the fatty acid substrate:
- 5-Lipoxygenase (5-LOX): Catalyzes the formation of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) from arachidonic acid.
- 12-Lipoxygenase (12-LOX): Catalyzes the formation of 12-hydroperoxyeicosatetraenoic acid (12-HPETE) from arachidonic acid.
- 15-Lipoxygenase (15-LOX): Catalyzes the formation of 15-hydroperoxyeicosatetraenoic acid (15-HPETE) from arachidonic acid.
Biological Significance
Lipoxygenases are involved in various physiological and pathological processes. In plants, they play a role in growth, development, and defense mechanisms against pathogens. In animals, lipoxygenases are involved in the regulation of inflammation and immune responses. Dysregulation of lipoxygenase activity has been implicated in several diseases, including asthma, arthritis, and cancer.
Clinical Implications
Inhibitors of lipoxygenases are being investigated as potential therapeutic agents for the treatment of inflammatory diseases, such as asthma and arthritis. By blocking the activity of lipoxygenases, these inhibitors can reduce the production of pro-inflammatory lipid mediators.
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