Inhibition of animal acetyl-coenzyme A carboxylase by 2-(p-chlorophenoxy)-2-methylpropionic acid and 2-ethylhexanoic acid.
Peroxisome proliferators are generally known as activators of fatty acid beta-oxidation which is one of degradation pathways. However, since it is unknown whether peroxisome proliferators have an effect on biosynthesis of fatty acid or not, we commenced to study if acetyl-CoA carboxylase, the rate-limiting enzyme of fatty acid biosynthesis, is inhibited by 2-(p-chlorophenoxy)-2-methylpropionic acid or 2-ethylhexanoic acid which is a typical peroxisome proliferator. Acetyl-CoA carboxylase(s) from rat, mouse, hamster, rabbit, dog and monkey were completely inhibited by 2-(p-chlorophenoxy)-2-methylpropionic acid or 2-ethylhexanoic acid at the concentration of 10(-3)M. For both compounds, there was not a large species difference in the inhibition. However, there was only several times difference between I50 values for the two compounds. The findings imply that inhibition of acetyl-CoA carboxylase by the chemicals leads to reduction of fatty acid biosynthesis when the chemicals are administered to the animals at high dose levels.
Sumida
K
K
Environmental Health Science Laboratory, Sumitomo Chemical Co. Ltd., Osaka, Japan.
Kaneko
H
H
Yoshitake
A
A
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D002208:Caproates / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002995:Clofibric Acid / Q000494:pharmacology*; D006224:Cricetinae; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007553:Isotope Labeling; D008253:Macaca mulatta; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008813:Mice, Inbred ICR; D008830:Microbodies / Q000187:drug effects*; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D002208:Caproates; D004791:Enzyme Inhibitors; C040668:2-ethylhexanoic acid; D002245:Carbon Dioxide; D002995:Clofibric Acid; D000103:Acetyl-CoA Carboxylase