5HETE

5HETE, or 5-hydroxyeicosatetraenoic acid, is a hydroxylated derivative of arachidonic acid and a member of the eicosanoid family. It is produced by cells of the immune system, especially leukocytes, through the lipoxygenase pathway. The natural form is primarily the 5S enantiomer in humans.

Biosynthesis and relationships to other eicosanoids: When arachidonic acid is acted on by 5-lipoxygenase (5-LO) in the presence of the 5-LO activating protein (FLAP), 5-HPETE (5-hydroperoxyeicosatetraenoic acid) is formed, which is subsequently reduced to 5HETE. 5-HPETE is also a branching point toward leukotriene synthesis, with 5-HPETE serving as a precursor to leukotriene A4 in the pathway toward LTBs and other downstream mediators. 5HETE can be further metabolized to more oxidized forms, such as 5-oxo-ETE, which has distinct receptor interactions.

Biological activity: 5HETE acts as a signaling molecule involved in inflammatory responses. It can promote neutrophil chemotaxis and contribute to vascular and inflammatory changes observed in inflammatory conditions. Its activity is enhanced when oxidized to 5-oxo-ETE, a potent activator of the oxoeicosanoid receptor (OXER1/GPR170) in various cells. In addition to cellular assays, 5HETE is detected in biological fluids during inflammatory states and is measured by chromatographic methods coupled to mass spectrometry.

Clinical and research relevance: 5HETE serves as a biomarker of lipoxygenase activity and inflammatory status in several conditions, including infections and chronic inflammatory diseases. It is generally studied within the broader context of arachidonic acid metabolism and leukotriene pathways rather than as a sole therapeutic target.