HPETEs

HPETEs, or hydroperoxyeicosatetraenoic acids, are a family of lipid hydroperoxide derivatives formed from arachidonic acid by lipoxygenase enzymes. The common members are 5-, 8-, 12-, and 15-HPETE, named for the position of the hydroperoxy group on the 20-carbon chain. HPETEs are transient intermediates rather than end products of the arachidonic acid cascade.

Biosynthesis of HPETEs begins when arachidonic acid is released from membrane phospholipids and oxygen is introduced by lipoxygenases. 5-LOX predominantly yields 5-HPETE, while 12-LOX and 15-LOX generate 12-HPETE and 15-HPETE, respectively. These hydroperoxides can be further processed enzymatically into hydroxyl derivatives (such as HETEs) or into other bioactive lipids. For example, 5-HPETE can be converted by additional enzymatic steps to leukotriene A4, a precursor to other leukotrienes, while 15-HPETE can participate in lipoxin formation through interactions with other lipoxygenases. Thus HPETEs occupy a central position in the network of pathways that produce inflammatory and resolving mediators.

Functionally, HPETEs act as reactive intermediates in lipid signaling and inflammation. Their downstream products, including leukotrienes, hydroxylated fatty acids, and lipoxins, have diverse roles in recruiting immune cells, regulating vascular tone, and resolving inflammatory responses. Because HPETEs can be unstable and readily transformed, their levels often reflect the activity of the lipoxygenase pathways and the oxidative environment of tissues.

In research and clinical contexts, HPETEs are typically measured to assess lipoxygenase activity or oxidative status. Alterations in HPETE metabolism have been explored in conditions such as asthma, inflammatory diseases, and cardiovascular disorders.