Prester_1991_Biochem.Pharmacol_42_2313

The inhibition of the human serum cholinesterase phenotypes, usual (U), atypical (A) and heterozygous (UA), by the dimethylcarbamate of (2-hydroxy-5-phenylbenzyl)-trimethylammonium bromide (Ro 02-0683), was followed with benzoylcholine, acetyl-, butyryl- and propionyl-thiocholine as substrates. The first-order rate constants were calculated from the linear part of the inhibition curves and were independent of the substrate used for measuring the enzyme activity. The second-order rate constants for the U, UA and A phenotypes were 8.3 x 10(6), 6.1 x 10(6) and 0.05 x 10(6) M-1 min-1, respectively. The constant of the enzyme-inhibitor complex for the atypical serum was 7.7 microM, and the rate of carbamylation of the enzyme was 0.386 min-1. The rate of reactivation of carbamylated usual and atypical enzyme was found to be same; the half-time of reactivation was about 3.5 hr. The deviation from the linearity of the inhibition course was explained by spontaneous reactivation of the inhibited enzyme; the theoretical inhibition curves were in good agreement with the experimentally obtained values. The three phenotypes could be distinguished by the rate of inhibition by the dimethylcarbamate, Ro 02-0683, in the progressive phase of inhibition or by the degree of inhibition in the apparent steady-state.