5HPETE

5-Hydroperoxyeicosatetraenoic acid (5-HPETE) is a hydroperoxide derivative of arachidonic acid produced by the enzyme 5-lipoxygenase (5-LOX) in various mammalian cells. It is an unstable intermediate in the leukotriene biosynthesis pathway, formed when 5-LOX catalytically inserts oxygen at the 5-position of arachidonic acid to yield a hydroperoxy eicosatetraenoic acid.

In the next step of the pathway, 5-HPETE is converted by leukotriene A4 synthase to leukotriene A4 (LTA4), an epoxide-containing intermediate that can be further processed to cysteinyl leukotrienes LTC4, LTD4, and LTE4, or hydrolyzed to other metabolites. Alternatively, cellular peroxidases can reduce 5-HPETE to 5-HETE, providing a competing route away from leukotriene formation. Thus, 5-HPETE serves as a branch point between pro-inflammatory leukotrienes and non-epoxide metabolites.

Physiological relevance: Through its role as a precursor to leukotrienes, 5-HPETE participates in inflammatory and allergic responses, including bronchoconstriction and leukocyte recruitment associated with asthma and other inflammatory conditions. Its accumulation is associated with conditions that upregulate 5-LOX activity, such as infection, tissue injury, and chronic inflammation.

Chemical and analytical aspects: As a reactive hydroperoxide, 5-HPETE is relatively labile and rapidly metabolized in biological systems. In research contexts, its detection and quantification typically rely on sensitive chromatographic methods coupled with mass spectrometry.