Arachidonic acid 15-hydroperoxide

Arachidonic acid 15-hydroperoxide (15-HPETE) is a hydroperoxide derivative of arachidonic acid, an essential polyunsaturated fatty acid involved in the biosynthesis of various eicosanoids. It is an important intermediate in the lipoxygenase pathway, which is responsible for the production of leukotrienes and other bioactive lipid mediators.

Biochemical Pathway

Arachidonic acid 15-hydroperoxide is formed through the action of the enzyme 15-lipoxygenase (15-LOX) on arachidonic acid. This enzyme catalyzes the oxygenation of arachidonic acid to produce 15-HPETE. The reaction involves the insertion of molecular oxygen into the 15th carbon of the arachidonic acid chain, resulting in the formation of a hydroperoxide group.

15-HPETE can be further metabolized into various other eicosanoids, including 15-hydroxyeicosatetraenoic acid (15-HETE) and lipoxins, which have roles in inflammation and resolution processes. The conversion of 15-HPETE to these products is mediated by specific enzymes, such as peroxidases and epoxide hydrolases.

Biological Functions

15-HPETE and its metabolites play significant roles in the regulation of inflammatory responses. They are involved in:

• Modulation of Inflammation: 15-HPETE can act as a precursor to anti-inflammatory lipoxins, which help resolve inflammation and promote tissue repair.
• Cell Signaling: As a lipid mediator, 15-HPETE influences various cell signaling pathways, affecting cell proliferation, apoptosis, and differentiation.
• Oxidative Stress: The hydroperoxide group in 15-HPETE can participate in redox reactions, contributing to oxidative stress and cellular damage if not properly regulated.

Clinical Relevance

The dysregulation of 15-HPETE and its metabolic pathways has been implicated in several diseases, including:

• Asthma: Abnormal production of leukotrienes from 15-HPETE can exacerbate inflammatory responses in the airways.
• Cardiovascular Diseases: Imbalances in eicosanoid production can affect vascular function and contribute to atherosclerosis.
• Cancer: Altered lipoxygenase activity and 15-HPETE levels have been associated with tumor progression and metastasis.

Research and Therapeutic Potential

Research into 15-HPETE and its derivatives is ongoing, with potential therapeutic applications in modulating inflammation and treating related disorders. Inhibitors of 15-lipoxygenase are being explored as potential drugs to reduce excessive eicosanoid production in inflammatory diseases.

Also see

• Arachidonic acid
• Lipoxygenase
• Eicosanoids
• Leukotrienes
• Inflammation