12-Hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid

12-Hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid

12-Hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HPETE) is a hydroperoxide derivative of arachidonic acid, an essential polyunsaturated fatty acid that plays a critical role in the biosynthesis of various eicosanoids. 12-HPETE is an important intermediate in the lipoxygenase pathway, which is involved in the production of leukotrienes, lipoxins, and other bioactive lipid mediators.

Structure and Nomenclature

12-HPETE is a 20-carbon fatty acid with four cis double bonds located at the 5, 8, 10, and 14 positions, and a hydroperoxy group at the 12 position. The systematic name reflects the positions and configurations of the double bonds and the hydroperoxy group:

• 12-hydroperoxy: indicating the presence of a hydroperoxy group at the 12th carbon.
• 5Z,8Z,10E,14Z: indicating the positions and configurations (Z for cis, E for trans) of the double bonds.
• eicosatetraenoic acid: indicating a 20-carbon chain with four double bonds.

Biosynthesis

12-HPETE is synthesized from arachidonic acid by the action of the enzyme 12-lipoxygenase (12-LOX). This enzyme catalyzes the insertion of molecular oxygen into arachidonic acid, forming the hydroperoxy group at the 12th carbon. The reaction can be summarized as follows:

Arachidonic acid + O₂ → 12-HPETE

Biological Functions

12-HPETE serves as a precursor for several biologically active compounds, including:

• 12-Hydroxyeicosatetraenoic acid (12-HETE): Formed by the reduction of 12-HPETE, 12-HETE is involved in various cellular processes, including inflammation and platelet aggregation.
• Lipoxins: Anti-inflammatory mediators that are synthesized from 12-HPETE through further enzymatic reactions.
• Leukotrienes: Although primarily derived from 5-HPETE, leukotrienes can also be influenced by the presence of 12-HPETE in certain pathways.

Clinical Significance

The metabolites of 12-HPETE, such as 12-HETE and lipoxins, have been implicated in various physiological and pathological processes, including:

• Inflammation: 12-HPETE and its derivatives play roles in modulating inflammatory responses.
• Cancer: Altered levels of 12-HPETE and its metabolites have been observed in certain types of cancer, suggesting a role in tumor progression and metastasis.
• Cardiovascular diseases: The balance of eicosanoids derived from 12-HPETE can influence cardiovascular health, affecting processes like vasodilation and platelet function.

Also see

• Arachidonic acid
• Lipoxygenase
• Eicosanoids
• 12-Hydroxyeicosatetraenoic acid
• Leukotrienes
• Lipoxins