This chapter describes the preparation and effects of 12-hydroxyeicosatetraenoic acid and related compounds. 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid is one of the major metabolites of arachidonic acid in many tissues or organs. It is the enzymatic product of a novel lipoxygenase present in platelets, leukocytes, spleen, lung, skin, and possibly other tissues. The initial oxygenation of arachidonic acid by the lipoxygenase produces 12-L-hydroxyperoxy-5,8,11,14-eicosatetraenoic acid (12-HPETE). The hydroxyperoxy precursor is subsequently reduced by a peroxidase to give the hydroxy acid. 12-HPETE has been detected in the incubation mixture of arachidonic acid and platelet homogenate. The other oxygenation pathway of arachidonic acid in these tissues is based on the cyclooxygenase. This enzyme catalyzes the transformation of substrate to prostaglandin endoperoxides PGGz and PGH2, which are the precursors of compounds of the prostaglandin family. The biological functions of the lipoxygenase pathway and its products have not been clearly defined, and there is considerable research effort directing toward this field.
