The kinetic study of the inhibition of human cholinesterases by demeton-S-methyl shows that cholinesterase-based titration methods are not suitable for this organophosphate

Bazire, A.; Gillon, Émilie; Lockridge, Oksana; Vallet, V.; Nachon, Florian

doi:10.1016/j.tiv.2011.01.006

Cited by 16 publications

(11 citation statements)

References 21 publications

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“…Kinetic behavior was characterized by a transitory inhibition with spontaneous reactivation, which had been also observed in cholinesterases (Eyer et al 2008;Bazire et al 2011). It has been suggested that these esterases play potential roles in toxicity and/or detoxication during lowdose long-term exposure to organophosphorus compounds, which warrants further toxicological and epidemiological research (Barril et al 1999;Estévez et al 2011).…”

Section: Introductionmentioning

confidence: 82%

Kinetics of inhibition of soluble peripheral nerve esterases by PMSF: a non-stable compound that potentiates the organophosphorus-induced delayed neurotoxicity

2012

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The kinetic analysis of esterase inhibition by acylating compounds (organophosphorus carbamates and sulfonyl fluorides) is sometimes unable to yield consistent results by fitting simple inhibition kinetic models to experimental data of complex systems. In this work, kinetic data were obtained for phenylmethylsulfonyl fluoride (PMSF) tested at different concentrations incubated for up to 3 h with soluble fraction of chicken peripheral nerve. PMSF is a protease and esterase inhibitor causing protection or potentiation of the organophosphorus-induced delayed neuropathy and is unstable in water solution. The target of the promotion effect was proposed to be a soluble esterase not yet identified. A kinetic model equation was deduced assuming a multienzymatic system with three different molecular phenomena occurring simultaneously: (1) inhibition, (2) spontaneous chemical hydrolysis of the inhibitor and (3) ongoing inhibition (inhibition during the substrate reaction). A three-dimensional fit of the model was applied for analyzing the experimental data. The best-fitting model is compatible with a resistant component (16.5-18%) and two sensitive enzymatic entities (both 41%). The corresponding second-order rate constants of inhibition (ki = 12.04 × 10⁻² and 0.54 × 10⁻² μM⁻¹ min⁻¹, respectively) and the chemical hydrolysis constant of PMSF (kh = 0.0919 min⁻¹) were simultaneously estimated. These parameters were similar to those deduced in fixed-time inhibition experiments. The consistency of results in both experiments was considered an internal validation of the methodology. The results were also consistent with a significant ongoing inhibition. The proportion of enzymatic components showed in this work is similar to those previously observed in inhibition experiments with mipafox, S9B and paraoxon, demonstrating that this kinetic approach gives consistent results in complex enzymatic systems.

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Section: Introductionmentioning

confidence: 82%

Kinetics of inhibition of soluble peripheral nerve esterases by PMSF: a non-stable compound that potentiates the organophosphorus-induced delayed neurotoxicity

2012

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“…In past, simple spectrophotometric tests based on 5,5 -dithiobis-(2-nitrobenzoic) acid as the chromogenic reagent and acetyl-(or butyryl-)thiocholine as the substrate (Ellman et al, 1961;George & Abernethy, 1983;Gorun et al, 1978), potentiometric tests with pH titration (Bazire et al, 2011), and electrochemical sensors and biosensors (Khaled et al, 2010;Pohanka, 2014) have been employed. The mentioned testes are based on an addition of reagents to the sample followed by measurements of the enzyme activity.…”

Section: Introductionmentioning

confidence: 99%

Determination of acetylcholinesterase and butyrylcholinesterase activity without dilution of biological samples

Pohanka

2015

Chemical Papers

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Two cholinesterases: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are known. The enzymes are important in the body and alteration of their activity has significant use in the diagnosis of poisoning, liver function, etc. Currently available methods for the determination of cholinesterases have some major drawbacks including various interferences and the inability to be used for decreasing the enzyme activity in the presence of reversible inhibitors due to sample dilution; hence, a method for dilution free assay of cholinesterases is desired. Here, microplates were modified with indoxylacetate (100 µL of 10 mmol L −1 solution) and used for cholinesterases assay after drying at 37 • C. The fact that indoxylacetate remains stable in dry state and serves simultaneously as a chromogen and substrate provide good prerequisites for the method. The limit of detection for BChE was 0.71 U while that for AChE was 2.8 U per a 100 µL sample (solution of enzyme or plasma sample). The limit of detection is low enough to allow standard examination of cholinesterasemia. The two cholinesterases can be distinguished from each other using selective inhibitors such as donepezil and iso-OMPA. The new method was also successfully validated for the standard Ellman's assay using plasma samples with BChE activity adjusted by carbofuran. The new method based on indoxylacetate seems promising for routine tests.

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“…However, because of wide inter-individual variability, significant depression of the enzyme cholinesterase activity may occur but still fall within the "normal" range [12]. Also, estimation of either serum EChE or BChE levels is costly and not regularly performed in most laboratories [13].…”

Section: Introductionmentioning

confidence: 99%

Correlation between Serum Creatine Phosphokinase and Severity of Acute Organophosphorus Poisoning: A Prospective Clinical Study (2012-2013

Hassan¹,

Madboly²

2013

IOSR-JESTFT

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The kinetic study of the inhibition of human cholinesterases by demeton-S-methyl shows that cholinesterase-based titration methods are not suitable for this organophosphate

Cited by 16 publications

References 21 publications

Kinetics of inhibition of soluble peripheral nerve esterases by PMSF: a non-stable compound that potentiates the organophosphorus-induced delayed neurotoxicity

Kinetics of inhibition of soluble peripheral nerve esterases by PMSF: a non-stable compound that potentiates the organophosphorus-induced delayed neurotoxicity

Determination of acetylcholinesterase and butyrylcholinesterase activity without dilution of biological samples

Correlation between Serum Creatine Phosphokinase and Severity of Acute Organophosphorus Poisoning: A Prospective Clinical Study (2012-2013

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