Rush_1981_J.Pharmacol.Exp.Ther_216_586

A new form of cholinesterases has been discovered in rabbit liver the new enzymes are monomeric butyrylcholinesterases EC 3.1.1.8 mBCHE I and mBCHE II These enzymes are inhibited reversibly by chlorpromazine in the pharmacologically active concentration range and they exhibit mixed competitive-noncompetitive inhibition patterns The apparent competitive inhibition constants Ki with chlorpromazine are 1.8 x 10 6 M for mBCHE I and 7.6 x 10(-6 M for mBCHE II whereas the noncompetitive inhibition constant is 1.1 x 10(-5 M for mBCHE II as determined by spectrophotometric assay with n-butyrylthiocholine iodide substrate Although inhibition of mBCHE I also a binding constant could not be determined Human serum oligometric butyrylcholinesterase oBCHE was employed as a control cholinesterase and also demonstrated mixed inhibition kinetics The competitive inhibition constant for the oBCHE was 5.5 x 10(-7 M in the low substrate region whereas the apparent noncompetitive binding constant was 1.6 x 10(-5 M in the activated higher substrate region with n-butyrylthiocholine iodide as the substrate and chlorpromazine as the reversible inhibitor The presence of a noncompetitive binding component indicates the presence of an operative modifier or allosteric site binding the inhibitor on both mBCHEs and the oBCHE The inhibition constants were calculated assuming that the enzymes followed simple Michaelian kinetics