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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
31
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pubmed:dateCreated |
1999-9-3
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pubmed:abstractText |
Reactivation of organophosphate (OP)-inhibited acetylcholinesterase (AChE) is a key objective in the treatment of OP poisoning. This study with native, wild-type, and mutant recombinant DNA-expressed AChEs, each inhibited by representative OP compounds, establishes a relationship between edrophonium acceleration of oxime-induced reactivation of OP-AChE conjugates and phosphoryl oxime inhibition of the reactivated enzyme that occurs during reactivation by pyridinium oximes LüH6 and TMB4. No such recurring inhibition could be observed with HI-6 as the reactivator due to the extreme lability of the phosphoryl oximes formed by this oxime. Phosphoryl oximes formed during reactivation of the ethoxy methylphosphonyl-AChE conjugate by LüH6 and TMB4 were isolated for the first time and their structures confirmed by (31)P NMR. However, phosphoryl oximes formed during the reactivation of the diethylphosphoryl-AChE conjugate were not sufficiently stable to be detected by (31)P NMR. The purified ethoxy methylphosphonyl oximes formed during the reactivation of ethoxy methylphosphonyl-AChE conjugate with LüH6 and TMB4 are 10- to 22-fold more potent than MEPQ as inhibitors of AChE and stable for several hours at pH 7.2 in HEPES buffer. Reactivation of both ethoxy methylphosphonyl- and diethylphosphoryl-AChE by these two oximes was accelerated in the presence of rabbit serum paraoxonase, suggesting that organophosphorus hydrolase can hydrolyze phosphoryl oxime formed during the reactivation. Our results emphasize that certain oximes, such as LüH6 and TMB4, if used in the treatment of OP pesticide poisoning may cause prolonged inhibition of AChE due to formation of phosphoryl oximes.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/7-((methylethoxyphosphinyl)oxy)-1-me...,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcholinesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Cholinesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Cholinesterase Reactivators,
http://linkedlifedata.com/resource/pubmed/chemical/DEP-2PAM,
http://linkedlifedata.com/resource/pubmed/chemical/Edrophonium,
http://linkedlifedata.com/resource/pubmed/chemical/HI 6,
http://linkedlifedata.com/resource/pubmed/chemical/Obidoxime Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Organophosphorus Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Oximes,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphorus Isotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridinium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolinium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/trimethylene-bis(4-hydroxyiminomethy...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-2960
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
38
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9937-47
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:10433700-Acetylcholinesterase,
pubmed-meshheading:10433700-Animals,
pubmed-meshheading:10433700-Cattle,
pubmed-meshheading:10433700-Cholinesterase Inhibitors,
pubmed-meshheading:10433700-Cholinesterase Reactivators,
pubmed-meshheading:10433700-Chromatography, High Pressure Liquid,
pubmed-meshheading:10433700-Edrophonium,
pubmed-meshheading:10433700-Enzyme Activation,
pubmed-meshheading:10433700-Fetal Blood,
pubmed-meshheading:10433700-Hydrolysis,
pubmed-meshheading:10433700-Kinetics,
pubmed-meshheading:10433700-Mice,
pubmed-meshheading:10433700-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:10433700-Obidoxime Chloride,
pubmed-meshheading:10433700-Organophosphorus Compounds,
pubmed-meshheading:10433700-Oximes,
pubmed-meshheading:10433700-Phosphorus Isotopes,
pubmed-meshheading:10433700-Pyridinium Compounds,
pubmed-meshheading:10433700-Quinolinium Compounds,
pubmed-meshheading:10433700-Recombinant Proteins
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pubmed:year |
1999
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pubmed:articleTitle |
Phosphoryl oxime inhibition of acetylcholinesterase during oxime reactivation is prevented by edrophonium.
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pubmed:affiliation |
Division of Biochemistry, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100, USA. dr.chunyanluo@wrsmtp-ccmail.army.mil
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pubmed:publicationType |
Journal Article
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