A STEREOSPECIFIC PHOSPHOTRIESTERASE IN HEN LIVER AND BRAIN

O-Hexyl, O-2,5-dichlorophenyl phosphoramidate (HDCP) is a chiral compo und that induces delayed neuropathy in hens. This compound is hydrolyz ed by a phosphotriesterase known as HDCPase in hen and rat plasma, liv er and brain. We studied the stereospecificity of HDCPase in hen tissu es and in human and rabbit plasma employing a chromatographic method f or analysis and quantification of HDCP stereoisomers. Hen and human pl asma HDCPases were not stereospecific. However, rabbit plasma showed a remarkable stereospecificity to S-(-)-HDCP. High levels of stereospec ific HDCPase were found in the particulate fraction of hen liver, wher e S-(-)-HDCP is hydrolyzed faster than R-(+)-HDCP. However, in hen bra in the stereospecificity was found in the soluble fraction, where R-()-HDCP is hydrolyzed faster than S-(-)-HDCP. It is concluded that live r particulate fraction must be the main tissue responsible for the HDC P stereospecific biotransformation in hens. In an oral administration, the steroisomer R-(+)-HDCP would survive after passing through the li ver and would interact with acetylcholinesterase and neuropathy target esterase in the nervous system. (C) 1998 Elsevier Science Ireland Ltd . All rights reserved.