Evidence that the conformational stability of ‘aged’ organophosphate-inhibited cholinesterase is altered

Masson, Patrick; Goasdoue, Jean-Louis

doi:10.1016/0167-4838(86)90070-1

Cited by 37 publications

(22 citation statements)

References 26 publications

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“…In the present study we operated under different conditions to overcome this complication. Therefore, the results we report confirm that denaturation of BuChE is a multistep process [15,30] and support the hypothesis that moderate pressures induce the sequential formation of at least two folding intermediates that may correspond to 'highly ordered' molten globule and molten globule states, respectively. The complete characterization of these intermediates is of outstanding interest.…”

Section: Resultssupporting

confidence: 74%

Pressure‐induced molten globule state of cholinesterase

1995

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The denaturing effect of pressure on the structure of human butyrylcholinesterase was examined by gel electrophoresis under pressure and by 8-anilino-l-naphthalene snlfonate (ANS) binding. It was found that the fluorescence intensity of bound ANS is increased by pressure between 0.5 and 1.5 kbar and that the hydrodynamic volume of the enzyme swells when pressures around 1.5 kbar are applied. These findings indicate that pressure denaturation of butyrylcholinesterase is a multi-step process and that the observed transient pressure-denatured states have characteristics of molten globules.

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Section: Resultssupporting

confidence: 74%

Pressure‐induced molten globule state of cholinesterase

1995

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“…However, enzyme denaturation studies showed that the conformational stability of aged cholinesterase is dramatically increased compared to non-inhibited and non-aged enzymes [84–87]. See Figure 9.…”

Section: Inhibition By Op and Aging Of The Inhibited Enzymementioning

confidence: 99%

Butyrylcholinesterase for protection from organophosphorus poisons: Catalytic complexities and hysteretic behavior

Masson

Lockridge

2010

Archives of Biochemistry and Biophysics

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199

135

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Butyrylcholinesterase is a promiscuous enzyme that displays complex kinetic behavior. It is toxicologically important because it detoxifies organophosphorus poisons (OP) by making a covalent bond with the OP. The OP and the butyrylcholinesterase are both inactivated in the process. Inactivation of butyrylcholinesterase has no adverse effects. However inactivation of acetylcholinesterase in nerve synapses can be lethal. OP-inhibited butyrylcholinesterase and acetylcholinesterase can be reactivated with oximes provided the OP has not aged. Strategies for preventing the toxicity of OP include a) treatment with an OP scavenger, b) reaction of nonaged enzyme with oximes, c) reactivation of aged enzyme, d) slowing down aging with peripheral site ligands, and e) design of mutants that rapidly hydrolyze OP. Option (a) has progressed through phase I clinical trials with human butyrylcholinesterase. Option (b) is in routine clinical use. The others are at the basic research level. Butyrylcholinesterase displays complex kinetic behavior including activation by positively charged esters, ability to hydrolyze amides, and a lag time (hysteresis) preceding hydrolysis of benzoylcholine and N-methyl indoxyl acetate. Mass spectrometry has identified new OP binding motifs on tyrosine and lysine in proteins that have no active site serine. It is proposed, but not yet proven, that low dose exposure involves OP modification of proteins that have no active site serine.

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“…After that, no treatment is possible due to dealkylation of organophosphate inside reactive site i.e. aging [20,21]. Activity of blood cholinesterases is considered as important marker of intoxication by organophosphates.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Cholinesterase Activities During in Vivo Intoxication Using an Electrochemical Sensor Strip – Correlation With Intoxication Symptoms

Pohanka

Novotný

Mišík

et al. 2009

Sensors

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Cholinesterase activity in blood of laboratory rats was monitored. Rats were intoxicated with paraoxon at dosis of 0 – 65 – 125 – 170 – 250 – 500 nmol. The 250 nmol dose was found to be the LD50. An electrochemical sensor was found useful to provide information about cholinesterase activity. The decrease of cholinesterase activity was correlated to intoxication symptoms and mortality level. It was found that the symptoms of intoxication are not observed while at least 50% of cholinesterase activity in blood remains. The minimal cholinesterase activity essential to survival is around 10%, when compared with the initial state. No changes in levels of low moleculary weight antioxidants were observed.

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Evidence that the conformational stability of ‘aged’ organophosphate-inhibited cholinesterase is altered

Cited by 37 publications

References 26 publications

Pressure‐induced molten globule state of cholinesterase

Pressure‐induced molten globule state of cholinesterase

Butyrylcholinesterase for protection from organophosphorus poisons: Catalytic complexities and hysteretic behavior

Evaluation of Cholinesterase Activities During in Vivo Intoxication Using an Electrochemical Sensor Strip – Correlation With Intoxication Symptoms

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