KINETICS OF HUMAN ERYTHROCYTE ACETYLCHOLINESTERASE INHIBITION BY A NOVEL DERIVATIVE OF PHYSOSTIGMINE - PHENSERINE

The effect of phenserine, a novel cholinesterase inhibitor, was assess ed for the first time on kinetic parameters of human erythrocyte acety lcholinesterase (AChE). Phenserine (0.025-0.40 mu M) inhibited the act ivity of human erythrocyte AChE in a concentration-dependent fashion, the IC50 was 0.0453 mu M. The Michaelis-Menten constant (K-m) for the hydrolysis of acetylthiocholine iodide was found to be 0.124 mM and th e V-max was 0.980 mu mol/min/mg protein. Dixon as well as Lineweaver-B urk plots and their secondary replots indicated that the nature of the inhibition was of the noncompetitive type. The value of K-i was estim ated as 0.048 mu M by the primary and secondary replots of the Dixon a s well as secondary replots of the Line Neaver-Burk plot. A novel rela tionship between K-i and substrate concentration was also identified w hich permits more precise prediction of the specific type of noncompet itive inhibition of various enzymes by a wide variety of drugs, chemic als and, in some circumstances, by their own substrates. (C) 1998 Acad emic Press.