US EPA

7431162 

Journal Article 

Anatoxin-a(s), a naturally occurring organophosphate, is an irreversible active site-directed inhibitor of acetylcholinesterase (EC 3.1.1.7) 

Hyde, EG; Carmichael, WW; , 

1991 

Yes 

Journal of Biochemical Toxicology
ISSN: 0887-2082
EISSN: 1522-7146 

VCH PUBLISHERS INC 

DEERFIELD BEACH 

6 

3 

195-201 

English 

1770503 

10.1002/jbt.2570060305 

WOS:A1991GJ33400004 

http://doi.wiley.com/10.1002/jbt.2570060305
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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). 

acetylcholinesterase; bacterial toxin; cholinesterase inhibitor; cyanobacterial toxin; marine toxin; animal; article; binding site; Cyanobacterium; drug effect; Electrophorus; metabolism; Acetylcholinesterase; Animal; Bacterial Toxins; Binding Sites; Cholinesterase Inhibitors; Cyanobacteria; Electrophorus; Marine Toxins; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.