DELAYED NEUROTOXIC EFFECT OF SOME ORGANOPHOSPHORUS COMPOUNDS - IDENTIFICATION OF PHOSPHORYLATION SITE AS AN ESTERASE
DELAYED NEUROTOXIC EFFECT OF SOME ORGANOPHOSPHORUS COMPOUNDS - IDENTIFICATION OF PHOSPHORYLATION SITE AS AN ESTERASE
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DOI：
10.1042/bj1140711
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发表时间：
1969-01-01
影响因子：
4.1
通讯作者：
JOHNSON, MK
中科院分区：
文献类型：
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作者：
JOHNSON, MK
1. 在母鸡体内产生延迟性神经毒性作用的有机磷化合物在给药后很快使大脑中的一个特定部位磷酸化。2. 二异丙基[32P]氟化磷对特定位点的体外磷酸化被事先添加的苯基苯乙酸酯阻断。3. 母鸡脑水解苯基苯乙酸体外总活性的一小部分被证明是由于一种不同于先前描述的其他两种酶。4. 当焦磷酸四乙酯和对氧磷（4-硝基苯基磷酸二乙基）的体外浓度达到64μm时，该酶仅被轻微抑制，而6μm-氟化磷酸二异丙基和128μm-米帕福斯则完全抑制该酶。5. 体内有效剂量的神经毒性有机磷化合物也能抑制它，但高剂量的非神经毒性类似物却不能。6. 推测该酶的活性位点是与迟发性神经毒性发生有关的磷酸化位点。
1. Organophosphorus compounds that produce a delayed neurotoxic effect in hens phosphorylate a specific site in the brain soon after administration. 2. Phosphorylation of the specific site by di-isopropyl [32P]phosphorofluoridatein vitrois blocked by the prior addition of phenyl phenylacetate. 3. A small proportion of the total activity of hen brain hydrolysing phenyl phenylacetatein vitrowas shown to be due to an enzyme different from two others previously described. 4. This enzyme is only slightly inhibitedin vitroby concentrations of tetraethyl pyrophosphate and paraoxon (diethyl 4-nitrophenyl phosphate) up to 64μmand is completely inhibited by 6μm-di-isopropyl phosphorofluoridate and 128μm-mipafox. 5. It is also inhibitedin vivoby effective doses of neurotoxic organophosphorus compounds but not by high doses of non-neurotoxic analogues. 6. It is deduced that the active site of this enzyme is the phosphorylation site associated with the genesis of delayed neurotoxicity.