Díaz-Alejo N, Monroy A, Vilanova E, Vicedo J L, Sogorb M A
Departmento de Neuroquímica, Universidad Miguel Hernández, San Juan de Alicante, Spain.
Chem Biol Interact. 1998 Jan 30;108(3):187-96. doi: 10.1016/s0009-2797(97)00106-3.
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.
O-己基-O-2,5-二氯苯基氨基磷酸酯（HDCP）是一种能在母鸡中诱发迟发性神经病变的手性化合物。该化合物在母鸡和大鼠的血浆、肝脏及大脑中可被一种名为HDCPase的磷酸三酯酶水解。我们采用一种色谱方法对HDCP立体异构体进行分析和定量，研究了母鸡组织以及人和兔血浆中HDCPase的立体特异性。母鸡和人血浆中的HDCPase没有立体特异性。然而，兔血浆对S-(-)-HDCP表现出显著的立体特异性。在母鸡肝脏的微粒体部分发现了高水平的立体特异性HDCPase，其中S-(-)-HDCP的水解速度比R-(+)-HDCP快。然而，在母鸡大脑中，立体特异性存在于可溶性部分，其中R-(+)-HDCP的水解速度比S-(-)-HDCP快。得出的结论是，肝脏微粒体部分必定是母鸡中HDCP立体特异性生物转化的主要负责组织。在口服给药时，立体异构体R-(+)-HDCP在经过肝脏后仍能留存，并会与神经系统中的乙酰胆碱酯酶和神经病变靶酯酶相互作用。
