Newly Observed Spontaneous Activation of Ethephon as a Butyrylcholinesterase Inhibitor

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• 作者：Mariya S. Liyasova ; Lawrence M. Schopfer ; Sean Kodani ; Stephen R. Lantz ; John E. Casida ; Oksana Lockridge
• 刊名：Chemical Research in Toxicology
• 出版年：2013
• 出版时间：March 18, 2013
• 年：2013
• 卷：26
• 期：3
• 页码：422-431
• 全文大小：326K
• 年卷期：v.26,no.3(March 18, 2013)
• ISSN：1520-5010

文摘

The plant growth regulator ethephon (2-chloroethylphosphonic acid) inhibits human butyrylcholinesterase (BChE) by making a covalent adduct on the active site serine 198. Our goal was to extend earlier studies on ethephon inhibition. Addition of freshly prepared ethephon to BChE in buffered medium, at pH 7.0 and 22 掳C, resulted in no inhibition initially. However, inhibition developed progressively over 60 min of incubation. Preincubation of ethephon in pH 7鈥? buffers increased its initial inhibitory potency. These observations indicated that ethephon itself was not the inhibitor. About 3% of the initial ethephon could be trapped as a BChE adduct. Mass spectral analysis of the active site peptide from inhibited BChE showed that the inhibitor added a mass of 108 Da to the active site serine on peptide FGES₁₉₈AGAAS. This result rules out a previous hypothesis that ethephon adds HPO₃ to BChE (added mass of 80 Da). To accommodate these observations, we propose that in aqueous media at neutral to slightly alkaline pH about 3% of the ethephon is converted (t_1/2 = 9.9 h at pH 7.0) into a cyclic oxaphosphetane which is the actual BChE inhibitor forming the 2-hydroxyethylphosphonate adduct on BChE at Ser198 while about 97% of the ethephon breaks down to ethylene (t_1/2 = 11鈥?8 h at pH 7.0) which is responsible for plant growth regulation.