Direct determination of the chemical composition of acetylcholinesterase phosphonylation products utilizing electrospray-ionization mass spectrometry

FEBS Letters
R BarakA Shafferman

Abstract

While non-reactivability of cholinesterases from their phosphyl conjugates (aging) is attributed to an unimolecular process involving loss of alkyl group from the phosphyl moiety, no conclusive evidence is available that this is the only reaction path and involvement of other post-inhibitory processes cannot be ruled out. To address this issue, molecular masses of the bacterially expressed recombinant human acetylcholinesterase and of its conjugates with a homologous series of alkyl methylphosphonofluoridates, were measured by electrospray-ionization mass spectrometry (ESI-MS). The measured mass of the free enzyme was 64,700 Da (calculated 64,695 Da) and those of the methylphosphono-HuAChE adducts, bearing isopropyl, isobutyl, 1,2-dimethylpropyl and 1,2,2-trimethylpropyl substituents, were 64,820, 64,840, 64,852 and 64,860 Da, respectively. These values reflect both the addition of the phosphonyl moiety and the gradual mass increase due to branching of the alkoxy substituent. The composition of these adducts change with time to yield a common product with molecular mass of 64,780 Da which is consistent with dealkylation of the phosphonyl moieties. Furthermore, in the case of 1,2-dimethylpropyl methylphosphono-HuAChE, the change...Continue Reading

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Citations

Jul 20, 2002·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Kouichiro Tsuge, Yasuo Seto
Jan 9, 2010·Environmental Health Perspectives·Charles M ThompsonKathleen M George
Nov 30, 2013·Biomedical Microdevices·Hsih Yin TanSum Huan Ng
Feb 24, 2012·Journal of Mass Spectrometry : JMS·Atsushi TakamizawaKenzo Hiraoka
Jul 31, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Amanda S Appel, Brian A Logue
Mar 30, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Kouichiro Tsuge, Yasuo Seto

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