Saturable binding sites for the coenzyme A ester of nafenopin, a peroxisome proliferator, in rat liver cytosol

Abstract

1. At least three different molecular weight binding sites exist in rat liver cytosol for nafenopin-CoA, the coenzyme A ester and metabolic product of the carcinogenic peroxisome proliferator nafenopin. No binding sites for the free drug were observed.

2. Polypeptides of 35–40 kDa molecular weight range where no acyl-CoA binding proteins have been previously described bind the highest proportion of nafenopin-CoA (60-70%). Binding is displaceable by the CoA esters of other peroxisome proliferators (ciprofibrate and tibric acid) and also by oleoyl-CoA but by palmitoyl-CoA. Direct binding studies show that 35–40-kDa polypeptides bind oleoyl-CoA but not oleic or palmitic acid, or palmitoyl-CoA.

3. Polypeptides of 10–14 and 65–70 kDa also bind nafenopin-CoA. However, in contrast with 35–40-kDa polypeptides they also bind oleic and palmitic acid as well as their correspondent acyl-CoA thioesters.