A stereospecific phosphotriesterase in hen liver and brain.
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.
Díaz-Alejo
N
N
Departmento de Neuroquímica, Universidad Miguel Hernández, San Juan de Alicante, Spain.
Monroy
A
A
Vilanova
E
E
Vicedo
J L
JL
Sogorb
M A
MA
D000818:Animals; D043303:Aryldialkylphosphatase; D001921:Brain / Q000201:enzymology*; D002645:Chickens; D002800:Cholinesterase Inhibitors / Q000378:metabolism; D004950:Esterases / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008099:Liver / Q000201:enzymology*; D009943:Organophosphorus Compounds / Q000378:metabolism; D010949:Plasma / Q000201:enzymology; D011817:Rabbits; D013237:Stereoisomerism
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; C066606:hexyl 2,5-dichlorophenylphosphoroamidate; D004950:Esterases; D043303:Aryldialkylphosphatase