Avtor/Urednik		Stojan, Jure
Naslov		The mechanism and benefit of human butyrylcholinesterase activation by what would otherwise be inhibitors
Tip		članek
Vol. in št.		, št. Vol. 308
Leto izdaje		2019
Obseg		str. 350-356
ISSN		0009-2797 - Chemico-biological interactions
Jezik		eng
Abstrakt		Activation of human butyrylcholinesterase by small quaternary ammonium ions is known. Here, additional ligands in this series are presented: edrophonium and choline, and the reactivator pyridine-2-aldoxime methochloride. Kinetic analysis of the progress curves with these compounds indicates the mechanism of enhanced deacylation by the ligand bound to the catalytic anionic site (Trp82) at the base of the active site. The larger, bis-quaternary ligands examined, as propidium, hexamethonium, decamethonium, and bis-thiocholine, show only competitive inhibition of butyrylcholinesterase, by preventing substrate approach. This hypothesis of enhanced deacylation was tested for reactivation of methanesulfonylfluoride-inactivated butyrylcholinesterase, a complex analogous to organophosphate-aged cholinesterases. The combination of substrate/products and pyridine-2-aldoxime methochloride improved butyrylcholinesterase activity over 2%h of continuous measurements, before which time substrate depletion prevailed. Similar reactivation of Torpedo californica acetylcholinesterase was unsuccessful, but both of these cholinesterases regain some activity if they have been inhibited and aged for days by diisopropylfluorophosphate.
Proste vsebinske oznake		butyrylcholinesterase cholinesterases aged enzyme butirilholinesteraza holinesteraza starostni encim