Evidence for multiple condensing enzymes in rat hepatic microsomes catalyzing the condensation of saturated, monounsaturated, and polyunsaturated acyl coenzyme A.
The condensation of palmitoyl-CoA with malonyl-CoA by rat hepatic microsomes was competitively inhibited by myristoyl-CoA, whereas it was noncompetitively inhibited by palmitoleoyl and gamma-linolenoyl-CoA. Furthermore, the condensation of palmitoleoyl-CoA with malonyl-CoA was also noncompetitively inhibited by gamma-linolenoyl-CoA. Replacement of normal diet by a fat-free high carbohydrate diet resulted in 8-, 2.5-, and 2.3-fold increases in the condensation rates of both palmitoyl- and myristoyl-CoA, palmitoleoyl-CoA, and gamma-linolenoyl-CoA, respectively. On the other hand, administration of di-(2-ethylhexyl)phthalate (DEHP) resulted in a 2-fold stimulation of the condensation activities with myristoyl- and palmitoyl-CoA, while those with palmitoleoyl- and gamma-linolenoyl-CoA decreased to about 83 and 63%, respectively. Similar results following dietary changes or DEHP administration were obtained for total elongation activities. Finally condensation activities of 16:0, 16:1, and gamma-18:3 CoA were differently affected by the proteolytic enzyme, chymotrypsin. The competitive substrate studies, those of dietary and DEHP administration, and the differential action of chymotrypsin strongly suggest the existence of at least three discrete condensing enzymes catalyzing the condensation of saturated, monounsaturated, and polyunsaturated acyl-CoAs. These studies also indicate that the condensation reaction is the regulating and rate-limiting step of the fatty acid chain elongation system.
D000214:Acyl Coenzyme A / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002918:Chymotrypsin / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D004051:Diethylhexyl Phthalate / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated; D007700:Kinetics; D008316:Malonyl Coenzyme A / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology*; D010169:Palmitic Acids / Q000494:pharmacology; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D051381:Rats
D000214:Acyl Coenzyme A; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005229:Fatty Acids, Monounsaturated; D010169:Palmitic Acids; D010171:Palmitoyl Coenzyme A; C008757:palmitoleic acid; C040349:S-tetradecanoyl-coenzyme A; C026562:linoleoyl-coenzyme A; D008316:Malonyl Coenzyme A; D004051:Diethylhexyl Phthalate; D002918:Chymotrypsin