title: Inhibition of AChE by malathion and some structurally similar compounds.
abstract: Inhibition of bovine erythrocyte acetylcholinesterase (free and immobilized on controlled pore glass) by separate and simultaneous exposure to malathion and malathion transformation products which are generally formed during storage or through natural or photochemical degradation was investigated. Increasing concentrations of malathion, its oxidation product malaoxon, and its isomerisation product isomalathion inhibited free and immobilized AChE in a concentration-dependent manner. KI, the dissociation constant for the initial reversible enzyme inhibitor-complex, and k3, the first order rate constant for the conversion of the reversible complex into the irreversibly inhibited enzyme, were determined from the progressive development of inhibition produced by reaction of native AChE with malathion, malaoxon and isomalathion. KI values of 1.3 x 10(-4) M(-1), 5.6 x 10(-6) M(-1) and 7.2 x 10(-6)M(-1) were obtained for malathion, malaoxon and isomalathion, respectively. The IC50 values for free/immobilized AChE, (3.7 +/- 0.2) x 10(-4) M/(1.6 +/-0.1) x 10(-4), (2.4 +/- 0.3) x 10(-6)/(3.4 +/- 0.1) x 10(-6)M and (3.2 +/- 0.3) x 10(-6) M/(2.7 +/- 0.2) x 10(-6) M, were obtained from the inhibition curves induced by malathion, malaoxon and isomalathion, respectively. However, the products formed due to photoinduced degradation, phosphorodithioic O,O,S-trimethyl ester and O,O-dimethyl thiophosphate, did not noticeably affect enzymatic activity, while diethyl maleate inhibited AChE activity at concentrations > 10mM. Inhibition of acetylcholinesterase increased with the time of exposure to malathion and its inhibiting by-products within the interval from 0 to 5 minutes. Through simultaneous exposure of the enzyme to malaoxon and isomalathion, an additive effect was achieved for lower concentrations of the inhibitors (in the presence of malaoxon/isomalathion at concentrations 2 x 10(-7) M/2 x 10(-7) M, 2 x 10(-7) M/3 x 10(-7)M and 2 x 10(-7) M/4.5 x 109-7) M), while an antagonistic effect was obtained for all higher concentrations of inhibitors. The presence of a non-inhibitory degradation product (phosphorodithioic O,O,S-trimethyl ester) did not affect the inhibition efficiencies of the malathion by-products, malaoxon and isomalathion.
authors.affiliation: Institute of Chemistry, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Danijela Z
authors.initials: DZ
authors.lastname: Krstić
authors.forename: Mirjana
authors.initials: M
authors.lastname: Colović
authors.forename: Mojca Bavcon
authors.initials: MB
authors.lastname: Kralj
authors.forename: Mladen
authors.initials: M
authors.lastname: Franko
authors.forename: Katarina
authors.initials: K
authors.lastname: Krinulović
authors.forename: Polonca
authors.initials: P
authors.lastname: Trebse
authors.forename: Vesna
authors.initials: V
authors.lastname: Vasić
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D008294:Malathion / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D010777:Photochemistry
chemical_list: D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D008294:Malathion