Hydrolysis of suxamethonium by different types of plasma

Abstract

1. A method, based on the use of the isolated frog rectus aibdominis preparation, is described for studying quantitatively the hydrolysis of suxamethonium at low concentrations. 2. Rates of hydrolysis of butyrylcholine, 10 mm, benzoylcholine, 0.05 mm, and suxamethonium, 0025 mM, by plasma from different species and human plasma with genetic variants of cholinesterase were measured. 3. The rates of hydrolysis of suxamethonium by different types of plasma vary widely. Human plasma with usual cholinesterase and monkey plasma hydrolyse suxamethonium more speedily than do the plasma of cats, dogs and rats, and human plasma with either atypical or fluoride resistant cholinesterase. This is only to a small extent attril'butable to differences in enzyme concentration and not explained by the presence of an inhibitor. 4. The Km values for butyrylcholine are very similar for different types of plasma but the K, values for suxamethonium in the system plasma-butyrylcholine-suxamethonium vary greatly. 5. These results and observations on the inhibition by decamethonium of the hydrolysis of butyrylcholine are consistent with the interpretation that the rates of hydrolysis of suxamethonium, 0.025 mm, obtained with different types of plasma vary because they are a function of two variables, the affinity of the ester for cholinesterase and the stability of the monosuccinyl derivative of the cholinesterase. It seems that human plasma with atypical cholinesterase hydrolyses suxamethonium much slower than does human plasma with usual cholinesterase mainly or solely because of differences in affinity of the ester for the two enzymes. On the other hand, cat plasma appears to hydrolyse suxamethonium much slower than does human plasma with usual cholinesterase mainly because the monosuccinyl derivative of cholinesterase in cat plasma is much more stable than that in human plasma. The reverse might apply for monkey plasma. 6. Inhibition by dibucaine or sodium fluoride of the hydrolysis of benzoylcholine is not a general guide to rates of hydrolysis of suxamethonium by different types of plasma.Suxamethonium (succinyldicholine; SDCh) is a neuromuscular blocking agent which is hydrolysed by acylcholine acyl-hydrolase (E.C.3.1.1.8; cholinesterase; butyrylcholinesterase) and thus has a brief duration of action. Enzymic hydrolysis

Stable Complexes Involving Acetylcholinesterase and Amyloid-β Peptide Change the Biochemical Properties of the Enzyme and Increase the Neurotoxicity of Alzheimer’s Fibrils

“…IC 50 values were calculated by logarithmic plot analysis. Inhibition coefficient values (K i ) were calculated from the equation K i ϭ IC 50 /1 ϩ (S/K m ), as described by Hobbiger and Peck (1969) where S represents the concentration of acetylthiocholine (0.75 mM), and K m represents the Michaelis-Menten constant.…”

Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis.

“…For example, some bisquaternary compounds, which are more potent inhibitors ofAcChoEase than their monoquaternary counterparts, bind poorly to BtChoEase (6). Human BtChoEase (h-BtChoEase) is of interest to anesthesiologists and geneticists because it is responsible for breakdown ofthe short-term muscle relaxant succinylcholine (7) and because numerous genetic variants exist in which the rate of succinylcholine hydrolysis is reduced (8).…”

Neuromuscular blocking activity of a new series of quaternary N‐substituted choline esters

“…Hobbiger & Peck (1969) have shown that the plasma cholinesterase of different species hydrolyses representative substrates at varying rates, the order for suxamethonium being monkey>man> rat>dog>cat. Other substrates were generally hydrolysed faster by man than by the latter species.…”