title: Inactivation of chicken liver fatty acid synthetase by malonyl coenzyme A. Effects of acetyl coenzyme A and nicotinamide adenine dinucleotide phosphate.
abstract: Chicken liver fatty acid synthetase complex is irreversibly inactivated by one of the substrates, malonyl-CoA. Acetyl-CoA has a dual role. At concentrations less than or comparable to those of malonyl-CoA, the rate of inactivation is enhanced, whereas at acetyl-CoA/malonyl-CoA ratios greater than 2, the rte of inactivation is slowed down. NADP+ at low concentrations (25 microM) affords considerable protection against malonyl-CoA mediated inactivation whereas NAD+ even at 1.0 mM concentration has no effect. The inactivation process does not lead to the dissociation of the enzyme complex and is accompanied by subtle conformational changes as measured by circular dichroism measurements. Of all the model partial reactions, decarboxylation of malonyl-CoA and the condensation--CO2 exchange are the only reactions which are not catalyzed by the modified species. The process of inactivation is accompanied by enhanced covalent binding of malonyl groups such that approximately 6 mol of the acyl group is bound per mol of the enzyme at complete inactivation. The available evidence suggests that the inactivation of the enzyme results from the binding of malonyl group(s) at or near the condensing site of the enzyme.
mesh_terms: D000105:Acetyl Coenzyme A / Q000494:pharmacology*; D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D002645:Chickens; D002942:Circular Dichroism; D004229:Dithiothreitol / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008316:Malonyl Coenzyme A / Q000494:pharmacology*; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology*; D010084:Oxidation-Reduction
chemical_list: D000214:Acyl Coenzyme A; D009243:NAD; D008316:Malonyl Coenzyme A; D009249:NADP; D000105:Acetyl Coenzyme A; D064429:Fatty Acid Synthases; D004229:Dithiothreitol