Discovery of Novel Brain Lipoxygenase Products Formed from Docosahexaenoic Acid (22:6w3)

It is known that alcohol exposure leads to a decline in brain docosahexaeonate (22:6w3). We hypothesized that alcohol could stimulate the metabolism of this polyunsaturated fatty to bioactive products. Several oxidized products of 22:6w3 were indeed observed when rat brain homogenate was incubated with 14C22:6w3 in vitro. A similar group of metabolites was formed in vivo from 14C-22:6w3 injected into the lateral ventricle. These metabolites were characterized by thermospray- and GC/MS as well as by the synthesis of standards using purified enzymes. Platelet lipoxygenase also proved useful in identifying one of the brain metabolites and served as a source of enzyme for preparative studies. Their physiological effects on smooth muscle tone and platelet aggregation will be presented.