Anatoxin-a(s), a naturally occurring organophosphate, is an irreversible active site-directed inhibitor of acetylcholinesterase (EC 3.1.1.7).
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| Abstract |
Anatoxin-a(s) is a guanidine methyl phosphate ester (unprotonated molecular ion equals 252 daltons) isolated from the freshwater cyanobacterium (blue-green alga) Anabaena flos-aquae strain NRC 525-17. Previous work has shown anatoxin-a(s) to be a potent irreversible inhibitor of electric eel acetylcholinesterase (EC 3.1.1.7, AChE). In the present study the interaction of anatoxin-a(s) with AChE was investigated by protection studies and since similarities have been noted between anatoxin-a(s) and the synthetic organophosphate anticholinesterases, the ability of reactivators to reactivate the inhibited enzyme was investigated. Treatments directed toward eliminating poisoning symptoms and in vivo protection from anatoxin-a(s) poisonings were investigated using oxime reactivators and atropine or pretreatment with a carbamate and atropine. Anatoxin-a(s) was shown to be an active site-directed inhibitor of acetylcholinesterase which is resistant to oxime reactivation due to the structure of its enzyme adduct. In vivo pretreatment with physostigmine and high concentrations of 2-PAM were the only effective antagonists against a lethal dose of anatoxin-a(s).
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| Authors | E G Hyde, W W Carmichael |
| Journal | Journal of biochemical toxicology (J Biochem Toxicol) Vol. 6 Issue 3 Pg. 195-201 ( 1991) ISSN: 0887-2082 [Print] United States |
| PMID | 1770503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.) |
| Chemical References |
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