Premium
THE PRIMARY BIOCHEMICAL LESION LEADING TO THE DELAYED NEUROTOXIC EFFECTS OF SOME ORGANOPHOSPHORUS ESTERS
Author(s) -
Johnson M. K.
Publication year - 1974
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1974.tb04404.x
Subject(s) - neurotoxicity , chemistry , esterase , phosphorylation , phosphoric acid , in vivo , enzyme , carbamate , hydrolysis , pharmacology , toxicity , organophosphate , biochemistry , biology , organic chemistry , pesticide , microbiology and biotechnology , agronomy
—In contrast with neurotoxic organophosphates of the type (RO) 2 P.O.X several phosphinates (R 2 P.O.X) cause prolonged inhibition of ‘neurotoxic esterase’ in vivo but do not cause delayed neurotoxicity even after repeated administration. Prior administration of these phosphinates protected hens against the neurotoxic effects of several organophosphates: this protection lasted until about 70 per cent of the enzyme site again became available for phosphorylation. In this respect phosphinates behave like carbamate and sulphonyl fluoride inhibitors of ‘neurotoxic esterase'. It is proposed that the development of delayed neurotoxicity requires phosphorylation of the esterase followed by hydrolysis of one remaining phosphoryl ester bond to produce a charged monosubstituted phosphoric acid group attached to the protein. Generation of such a group could not occur after inhibition by the protective phosphinates, carbamates or sulphonates. It is proposed that the charged group is responsible for the metabolic disturbance leading to degeneration of long axons.