title: Substrate-dependent kinetic behavior of horse plasma cholinesterase: evidence for kinetically distinct populations of active sites.
abstract: The inhibition of horse plasma cholinesterase by propranolol showed characteristics which depended upon the identity of the substrate used. With butyrylthiocholine as substrate, the inhibition showed a first-order dependence on inhibitor concentration, and was characterized by a Ki of 8 microM (pH 7.4, 20 degrees C). With p-nitrophenylbutyrate as substrate, a biphasic v-1 versus [I] relationship was obtained. The biphasic curve could be resolved into two components, with apparent Ki's of 9 microM and 1.3 mM. Use of butyrylthiocholine as alternative substrate resulted in partial inhibition of p-nitrophenylbutyrate hydrolysis. Inhibition of butyrylthiocholine hydrolysis by p-nitrophenylbutyrate could be accounted for by pure competitive inhibition at two sites. The results were interpreted in terms of a four-site, low-symmetry model, in which two active sites could process both substrates, and the remaining sites could process only p-nitrophenylbutyrate.
mesh_terms: D000495:Allosteric Site; D000818:Animals; D001667:Binding, Competitive; D002092:Butyrylthiocholine / Q000097:blood / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases / Q000097:blood*; D006736:Horses; D006868:Hydrolysis; D007700:Kinetics; D010654:Phenylbutyrates / Q000097:blood / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013379:Substrate Specificity
chemical_list: D002800:Cholinesterase Inhibitors; D010654:Phenylbutyrates; C016013:2-nitrophenyl butyrate; D002092:Butyrylthiocholine; D011433:Propranolol; D002802:Cholinesterases