Johnson M K
Monogr Neural Sci. 1980;7:99-105.
Organophosphorus compounds which cause delayed neurotoxic effects phosphorylate a characteristic nervous-tissue protein and inhibit its activity as an esterase. Studies with a variety of inhibitors reveal that the toxic effect does not occur because of the loss of esterase activity but depends on the chemistry of the inhibited enzyme. A process analogous to the 'aging' of inhibited cholinesterase occurs after neurotoxic esterase has been inhibited by neurotoxic agents which leaves a charged acidic group attached to the membrane-bound esterase. This charge could disrupt normal metabolism in the neurone. Protective compounds inhibit neurotoxic esterase but the 'aging' process cannot occur, so that there is no formation of a charged group. Neurotoxic esterase occurs widely in the brain. Attempts are being made to locate the enzyme intraneuronally. The present understanding is of great value in toxicology. However, it has not yet clarified the physiological processes which maintain long axons in normal health.
引起迟发性神经毒性作用的有机磷化合物会使一种特定的神经组织蛋白磷酸化，并抑制其作为酯酶的活性。对多种抑制剂的研究表明，毒性作用并非由于酯酶活性丧失而发生，而是取决于被抑制酶的化学性质。在神经毒性酯酶被神经毒性剂抑制后，会发生一个类似于被抑制胆碱酯酶“老化”的过程，这会使一个带电荷的酸性基团附着在膜结合酯酶上。这个电荷可能会扰乱神经元中的正常代谢。保护化合物会抑制神经毒性酯酶，但“老化”过程不会发生，因此不会形成带电荷的基团。神经毒性酯酶广泛存在于大脑中。人们正在尝试在神经元内定位该酶。目前的认识在毒理学中具有重要价值。然而，它尚未阐明维持长轴突正常健康状态的生理过程。
