Modification of the kinetic properties of Triton-solubilized rabbit brain acetylcholinesterase by allosteric effectors at low ionic strength.
Gallamine and tubocurarine increased the rate of decarbamylation of carbamylated Triton-solubilized rabbit brain acetylcholinesterase and interacted synergistically with 3,3-dimethyl-1-butanol in the acceleration of decarbamylation at low ionic strength. Gallamine and tubocurarine also accelerated decarbamylation at a physiological ionic strength, but in this case the interaction with 3,3-dimethyl-1-butanol was not synergistic. Tubocurarine decreased the rate of ageing of isopropylmethyl-phosphonyl-acetylcholinesterase at low ionic strength, but gallamine and tubocurarine had no effect on ageing at a physiological ionic strength, nor did gallamine at low ionic strength. However reductions in the rate of ageing were observed for gallamine/3,3-dimethyl-1-butanol and tubocurarine/3,3-dimethyl-1-butanol mixtures at low ionic strength. Gallamine increased the maximum velocity of hydrolysis of acetylthiocholine at low ionic strength, but not at physiological ionic strength. Gallamine increased the rate of carbamylation of acetylcholinesterase by physostigmine and neostigmine at low ionic strength; however the data were not consistent with a simple model of complexing inhibition by these carbamates. Overall, the kinetic properties of Triton-solubilized rabbit brain acetylcholinesterase were less sensitive to modification by proposed allosteric effectors than bovine erythrocyte acetylcholinesterase, the allosteric properties of which have been reported previously, and millimolar concentrations of gallamine and tubocurarine were required to produce observable effects at physiological ionic strength. Further experiments are required to determine whether acetylcholinesterase is similarly insensitive to allosteric regulation in vivo.
Dawson
R M
RM
Materials Research Laboratory, Defence Science and Technology Organization, P.O. Box 50, Ascot Vale, Victoria 3032, Australia.
Gray
P J
PJ
Upsher
C M
CM
Michaelson
S
S