Arachidonate 15-lipoxygenase

Arachidonate 15-lipoxygenase

Arachidonate 15-lipoxygenase (ALOX15) is an enzyme that plays a crucial role in the metabolism of polyunsaturated fatty acids, particularly arachidonic acid. It is a member of the lipoxygenase family of enzymes, which are responsible for the oxygenation of fatty acids to form hydroperoxy derivatives. ALOX15 specifically catalyzes the conversion of arachidonic acid to 15-hydroperoxyeicosatetraenoic acid (15-HPETE), which can be further metabolized into various bioactive lipid mediators.

Function

ALOX15 is involved in the biosynthesis of eicosanoids, which are signaling molecules that exert complex control over many bodily systems, including inflammation and immunity. The enzyme is expressed in various tissues, including the lungs, skin, and reticulocytes, and is known to participate in the resolution of inflammation by producing anti-inflammatory lipid mediators such as lipoxins.

Mechanism of Action

ALOX15 catalyzes the insertion of molecular oxygen into arachidonic acid at the C-15 position, resulting in the formation of 15-HPETE. This reaction involves the abstraction of a hydrogen atom from the substrate, followed by the addition of oxygen. The enzyme contains a non-heme iron at its active site, which is essential for its catalytic activity.

Clinical Significance

Dysregulation of ALOX15 activity has been implicated in various diseases, including asthma, atherosclerosis, and certain types of cancer. The enzyme's role in the production of pro-resolving lipid mediators makes it a potential target for therapeutic intervention in inflammatory diseases.

Genetic Information

The human ALOX15 gene is located on chromosome 17p13.3. It is highly conserved across species, indicating its important biological function. Variations in the ALOX15 gene have been studied in relation to susceptibility to inflammatory diseases and metabolic disorders.

Research and Development

Current research on ALOX15 focuses on understanding its role in disease pathogenesis and exploring its potential as a drug target. Inhibitors of ALOX15 are being investigated for their therapeutic potential in treating inflammatory and proliferative diseases.

Also see

• Lipoxygenase
• Arachidonic acid
• Eicosanoid
• Inflammation
• Lipoxin