INDUCTION OF (OMEGA-1)-OXIDATION OF MONOCARBOXYLIC ACIDS BY ACETYLSALICYLIC-ACID

Monocarboxylic acids may be oxidized at the omega- and (omega-1)- posi tions to form dicarboxylic acids (DCAs) and (omega-1)-hydroxy- or (ome ga-1)-oxoacids. The significance of this pathway under normal conditio ns is unknown, but DCAs and (omega-1)-hydroxyacids are prominent featu res of disease states. The stimulation of this pathway has been linked to induction of fatty acid-binding protein and peroxisomal proliferat ion. In this study, we examined the effect of acetylsalicylic acid (AS A) on (omega-1)-oxidation. (Omega-1)-oxidation was assessed in subcell ular fractions of rat liver. Rats were fed a normal diet or an ASA-sup plemented diet. Products were identified by gas chromatography-mass sp ectrometry (GC-MS) and by comparison with the properties of authentic synthetic standards. Doses of ASA that produced relatively low serum c oncentrations (12-24 mg/dl) resulted in as much as a 20-fold increase in the capacity for (omega-1)-oxidation of medium (C12-C15) and long c hain (C16-C20) monocarboxylic acids. Normal rat liver oxidizes monocar boxylic acids to (omega-1)-oxoacids, while liver from ASA-treated rats converts these substrates to (omega-1)-oxodicarboxylic acids and (ome ga-1)-oxoacids. The formation of oxoacids and oxodicarboxylic acids ma y be due to different enzymes. The formation of oxodicarboxylic acids appears to be more labile than the formation of oxoacids. These two pr ocesses also are differentially induced by ASA and have different subs trate specificities. These results demonstrate that ASA is a potent st imulant of (omega-1)-oxidation and induces the formation of products t hat can be shortened in peroxisomes to key metabolic intermediates.