[1] However, cells undergoing aging, senescence, apoptosis, oxidative stress, or other conditions that raise their levels of reactive oxygen species (e.g. superoxide anion, oxygen radicals, and peroxides) either physiologically (e.g. human phagocytes engulfing bacteria) or pathologically (e.g. oxidatively challenged B-lymphocytes) use up NADP+, have low NADPH/NADP+ ratios, and therefore readily convert 5(S)-HETE to 5-oxo-ETE.

[1] Thus, many pathological conditions that involve oxidative stress such as occurs in rapidly growing cancers may be important promoters of 5-oxo-ETE accumulation in vivo.

5-Oxo-ETE can also be made from either 5(S)-HpETE (and possibly 5(R)-HpEPE) by the action of cytochrome P450 (CYP) enzymes such as CYP1A1, CYP1A2, CYP1B1, and CYP2S1;[4] from 5(S)-HETE (and probably 5(R)-HETE) by the non-enzymatic attack with heme or various other dehydrating agents.

This byproduct differs from 5-oxo-ETE not only in the position and geometry of its double bounds but also in its activity: it stimulates human neutrophils apparently by acting on one or more LTB4 receptors rather than OXER1.

[3][7] It is theorized that this transcellular metabolism occurs in vivo and provides a mechanism for controlling 5-oxo-ETE production by allowing it to occur or be augmented at sites were 5-lipoxygenase-containing cells congregate with cell types possessing 5-HEDH and favorable NADPH/NADP+ ratios; such sites, it is theorized, might include those involving allergy, inflammation, oxidative stress, and rapidly growing cancers.

[10][11] Studies in human neutrophils first detected a plasma membrane-localized site which reversibly bound 5-oxo-ETE and had the attributes of a Gi alpha subunit-linked G protein-coupled receptor based on the ability of 5-oxo-ETE to activate this class of membrane G proteins by a pertussis toxin-sensitive mechanism.

[3][17] 5-Oxo-ETE is a potent in vitro stimulator and/or enhancer of chemotaxis (i.e. directional migration) and, depending on the cell type, various other responses such as degranulation (i.e. release of granule-bound enzymes), oxidative metabolism (i.e. generation of reactive oxygen species), and production of mediators such as various arachidonic acid metabolites and platelet-activating factor in human eosinophils, basophils, neutrophils, and monocytes.

[3][18] Furthermore, the injection of 5-oxo-ETE into the skin of humans causes the local accumulation of circulating blood cells, particularly eosinophils but also to lesser extents neutrophils and monocyte-derived macrophages.

[3][20] These results suggest that 5-oxo-ETE is not directly involved in the bronchoconstriction) that occurs in eosinophil-based allergic asthma reactions in humans.

5-Oxo-ETE (or other 5-HETE family member) stimulates the growth and/or survival of human cell lines derived from cancers of the prostate, breast, lung, ovary, colon and pancreas[1][3][16][21] These preclinical studies suggest that 5-oxo-ETE (or other 5-HETE family member) may contribute to the cited cancers progression in humans.

5-oxo-ETE stimulates human H295R adrenocortical cells to increase transcription of steroidogenic acute regulatory protein messenger RNA and produce aldosterone and progesterone by an apparent OXER1-dependent pathway.

Translation studies are needed to learn if the preclinical studies implicating 5-Oxo-ETE and other 5(S)-HETE family members in allergic diseases, inflammatory diseases, cancer, steroid production, bone remodeling, parturition, and other pathophysiological events, as outlined here and on the 5-HETE page, are relevant to humans and therefore of clinical significance.

This same receptor antagonist likewise blocked the infiltration of eosinophils into the lung in rhesus monkeys that were sensitized to and then challenged with the original allergen.

Increased levels of 5-oxo-ETE have been detected in the exhaled breath condensate of humans who developed an asthma-like bronchoconstriction response to the inhalation of house dust mite allergen: the levels of these increases were higher in individuals who developed a more severe late asthmatic response.