STEREOCHEMICAL ASPECTS OF FATTY-ACID OXIDATION - HYDROPEROXIDE ISOMERASES

Lipoxygenases catalyze dioxygenation of polyunsaturated fatty acids to produce fatty-acid hydroperoxides. The reaction involves initial ster eospecific abstraction of a hydrogen atom from a bis-allylic methylene group followed by antarafacial attack by dioxygen at one of the termi nal carbon atoms of the pentadienyl radical. 8(R)-Dioxygenase, recentl y discovered in the fungus Gaeumannomyces graminis, catalyzes formatio n of 8-hydroperoxy derivatives of linoleic and oleic acids by abstract ing one hydrogen from C-8 and inserting dioxygen at the same carbon at om. Isotope-labeling studies show that the configuration at C-8 is inv erted during this process. The fungus Saprolegnia parasitica, a fish p arasite, contains an omega 6-lipoxygenase and an epoxy alcohol synthas e. The latter enzyme catalyzes isomerization of fatty acid hydroperoxi des into alpha,beta- and gamma,delta-epoxy alcohols. Experiments with O-18-labelled hydroperoxides demonstrate that the hydroperoxide --> ep oxy alcohol conversion consists of intramolecular transfer of the term inal hydroperoxide oxygen to either of the two conjugated double bonds . The reactions proceed with retention of geometrical configuration, i .e. epoxidation of the alpha,beta (E) and gamma,delta (Z) double bonds of the parent fatty acid hydroperoxide gives rise to trans and cis ep oxides, respectively. G. graminis, as well as the marine red alga Grac ilariopsis lemaneiformis, contain vicinal diol synthases that catalyze isomerization of fatty-acid hydroperoxides into vicinal dihydroxy fat ty acids. Studies using O-18-labelled hydroperoxides show that the hyd roperoxide --> diol conversions occur by intramolecular transfer of th e terminal hydroperoxide oxygen to the vicinal methylene group. Experi ments with stereospecifically deuteriated fatty-acid hydroperoxides de monstrate that the intramolecular hydroxylations catalyzed by the two vicinal diol synthases proceed with retention of absolute configuratio n of the carbon hydroxylated.