Aging nerve agent-acetylcholinesterase

Millard, C.B., Kryger, G., Ordentlich, A., Greenblatt, H.M., Harel, M., Raves, M.L., Segall, Y., Barak, D., Shafferman, A., Silman, I., Sussman, J.L. (1999a). Crystal structures of aged phosphonylated acetylcholinesterase nerve agent reaction products at the atomic level. Biochemistry 38 7032-9. 

I., Sussman, J.L. (1999). Crystal stmctures of aged phospho-nylated acetylcholinesterase nerve agent reaction products at the atomic level. Biochemistry 38 7032-9. 

Pralidoxime improves the patient s muscle strength by removing the nerve agent from acetylcholinesterase. The acetylcholinesterase, when freed from the nerve agent, then resumes breakdown of acetylcholine. Pralidoxime s effectiveness decreases with time, because the enzyme/nerve agent complex can age and form an irreversible bond. The time course for this depends on the specific agent and can vary from minutes to hours. 

The fundamental processes involved in acetylcholinesterase (AChE) inhibition, reactivation and ageing , are similar for both nerve agents... 

Luo, C., Tong, M., Maxwell, D.M., et al., 2008. Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases. Chem. Biol. Interact. 175, 261-266. 

---