Conference paper

The Comparative Biochemistry of Mammalian and Insect Acetylcholinesterase with Reference to the Selective Inhibition by Organophosphates and Carbamates

Klaus Hellenbrand ; Nova Scotia Research Foundation, Box 790, Dartmouth, Nova Scotia, Canada
Richard M. Krupka ; Agricuiture Canada, Research Laboratory, London, Ontario, Canada

Abstract

Acetylcholinesterases from bovine erythrocytes and housefly
heads are compared with respect to binding of substrates and
reversible cationic inhibitors, effects of the latter on reaction with
methane sulfonyl fluoride, and inactivation by organophosphofus
and carbamate inhibitors. The observations show that a hydrophobic
region is present outside the catalytic centre, which is considerably
broader and more accessible in the insect enzyme. Phosphate
and carbamate inhibitors can interact productively with
this region, whereas such interactions would be detrimental to true
substrates, diminishing their rates of reaction. It is this broader
hydrophobic region, rather than wider separation of the anionic and
esteratic sites, that accounts for acceleration of methane sulfonyl
fluoride reaction by large cations and accommodation of bulky
irreversible inhibitors in fly acetylcholinesterase. It is concluded
that the greater selectivity for fly acetylcholinesterase of many
organophosphates and carbamates may primarily depend on recognition
of distinctive features around, rather than in, the active
centre.

Keywords

Hrčak ID:

196611

URI

https://hrcak.srce.hr/196611

Publication date:

3.12.1975.

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