The substrate specificity of 5-HEDH has been evaluated in a variety of intact cells and in crude microsome preparations isolated from cultured human blood monocytes differentiated into macrophages.
[1][2][3] 5-HEDH is therefore hydroxy dehydrogenase that acts in a stereospecific manner to oxidize 5(S)-hydoxy residues in 6-trans unsaturated intermediate but not short-chain fatty acids.
However, cells suffering oxidative stress generate excesses in toxic reactive oxygen species such as hydrogen peroxide (H2O2).
While cells suffering oxidative stress can replenish NADPH by reducing NADP+ through the pentose phosphate pathway, they often develop very high NADP+/NADPH ratios and therefore preferentially convert 5-(S)-HETE to 5-oxo-ETE.
Furthermore, 5-oxo-ETE appears to be involved in various animal and human reactions: injected into the skin of rabbits, it causes a severe edema with an inflammatory cell infiltrate resembling an urticaria-like lesion;[13] it is present in bronchoalveolar lavage fluid from cats undergoing experimentally induced asthma;[14] it stimulates the local accumulation of eosinophils, neutrophils, and monocytes when injected into the skin of humans;[15] and it has been extracted from scales of psoriatic patients.
[16] Most if not all of these allergic and inflammatory conditions as well as rapidly growing cancerous lesions are associated with oxidative stress.
[17] Studies therefore suggest that 5-HEDH contributes to the development and progression of these reactions and diseases by being responsible for generating 5-oxo-ETE.