Saturable binding sites for the coenzyme A ester of nafenopin, a peroxisome proliferator, in rat liver cytosol.
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.
Morgan
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Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Bronfman
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D000105:Acetyl Coenzyme A / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002850:Chromatography, Gel; D003600:Cytosol / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D009255:Nafenopin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
D000214:Acyl Coenzyme A; D000960:Hypolipidemic Agents; D011506:Proteins; D009255:Nafenopin; D014316:Tritium; C051515:nafenopin-coenzyme A; D000105:Acetyl Coenzyme A