Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro and in vivo biochemical properties of O-hexyl, O-dichlorophenyl phosphoramidate (hexyl-DCP) as inhibitor of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) were studied, as well as their neurotoxic effects. The differences found were suggested to be due to biotransformation effects. In this work, the in vitro time-dependent degradation of hexyl-DCP by plasma, liver and brain homogenates of rat and hen at 37 degrees C at pH 7.4 are studied using 100 nM initial concentration. The loss of inhibitory potency against AChE was used as sensor of the biodegradation rate. An approximate estimation of the residual compound was made by comparison with an inhibition calibration curve. The rate of enzymatic degradation was corrected for the spontaneous hydrolysis. Rat tissues showed some higher activities (24, 17, 1 mU/g for plasma, liver, and brain, respectively) than hen (17, 6, 1 mU/g), with activities being highest for plasma and lowest for brain. Hexyl-DCP is a chiral compound. The loss of anti-AChE power could be due to degradation of only one of the two stereoisomers.
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PMID:Hen liver and plasma can metabolize hexyl-DCP phosphoramidate at a rate comparable to that of rat. 225 3

O-Hexyl, O-2,5-dichlorophenyl phosphoramidate (HDCP) is a chiral compound that induces delayed neuropathy in hens. This compound is hydrolyzed by a phosphotriesterase known as HDCPase in hen and rat plasma, liver and brain. We studied the stereospecificity of HDCPase in hen tissues and in human and rabbit plasma employing a chromatographic method for analysis and quantification of HDCP stereoisomers. Hen and human plasma HDCPases were not stereospecific. However, rabbit plasma showed a remarkable stereospecificity to S-(-)-HDCP. High levels of stereospecific HDCPase were found in the particulate fraction of hen liver, where S-(-)-HDCP is hydrolyzed faster than R-(+)-HDCP. However, in hen brain the stereospecificity was found in the soluble fraction, where R-(+)-HDCP is hydrolyzed faster than S-(-)-HDCP. It is concluded that liver particulate fraction must be the main tissue responsible for the HDCP stereospecific biotransformation in hens. In an oral administration, the steroisomer R-(+)-HDCP would survive after passing through the liver and would interact with acetylcholinesterase and neuropathy target esterase in the nervous system.
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PMID:A stereospecific phosphotriesterase in hen liver and brain. 952 89