Butyrylcholinesterase aging

Nachon F, Asojo OA, Borgstahl G, Masson P, Lockridge O (2005) Role of water in aging of human butyrylcholinesterase inhibited by echothiophate the crystal structure suggests two alternative mechanisms of aging, Biochemistry 44 1154-1162... 

A major drawback of the fluoride reactivation method is that not all nerve agent adducts are amenable to fluoride reactivation, with the aged adduct of soman the best known example. This problem can be solved by looking at the BuChE enzyme itself Fidder et al (2002) published a method based on the LC-MS analysis of a nerve agent phosphylated nonapeptide derived after pepsin digestion of inhibited butyrylcholinesterase. The authors presented a procedure to extract BuChE from plasma using... 

OPs bound to tyrosine do not age. Aging of OP adducts on acetylcholinesterase and butyrylcholinesterase is defined as the loss of an alkoxy group from the phosphorus atom. Every OP-tyrosine adduet in Table 56.1 has been examined... 

FIGURE 57.9. Inhibition and aging of serine esterases by diisopropylphosphorofluoridate (DFP). The active site serine is organophosphorylated in the inhibition step. Aging results in net loss of an isopropyl group to yield the monoisopropylphosphoryl esterase. This mode of inhibition and aging has been established for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and neuropathy target esterase catalytic domain (NEST) (Kropp and Richardson, 2007). 

Kropp, T.J., Richardson, R.J. (2007). Mechanism of aging of mipafox-inhibited butyrylcholinesterase. Chem. Res. Toxicol. 20 504-10. 

Li, H., Schopfer, L.W., Nachon, F., Froment, M-T., Masson, P., Lockridge, O. (2007). Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometry. Toxicol. Sci. 100 136 5. 

Wandhammer, M., De Koning, M., van Grol, M., et al., 2013. A step toward the reactivation of aged cholinesterases—crystal structure of ligands binding to aged human butyrylcholinesterase. Chem. Biol. Interact. 203, 19-23. 

Jiang, W., Cashman, J.R., Nachon, F., et al., 2013. Mass spectrometry method to identify aging pathways of SP- and RP-tabun adducts on human butyrylcholinesterase based on the acid labile P-N bond. Toxicol. Sci. 132, 390-398. 

Jiang, W., Murashko, E.A., Dubrovskii, Y.A., et al., 2013. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of titanium oxide-eiuiched peptides for detection of aged organophosphorus adducts on human butyrylcholinesterase. Anal. Biochem. 439,132-141. 

Masson, P., Fortier, P.L., Albaret, C., et al., 1997. Aging of di-isopropyl-phosphor-ylated human butyrylcholinesterase. Biochem. J. 327, 601-607. 

E. Carletti, N. Aurbek, E. Gillon, M. Loiodiee, Y. Nicolet, J. C. Fontecil-la-Camps, P. Masson, H. Thiermann, F. Naehon and F. Worek, Structure-activity analysis of aging and reactivation of human butyrylcholinesterase inhibited by analogues of tabun, Biochem.J, 2009,421,97-106. 

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