The mechanism of ageing of phosphonylated acetylcholinesterase.
1. The extent of potential reactivation of organophosphate-inhibited acetylcholinesterase decreases with time, a phenomenon called ageing. Ageing is due to dealkylation of the alkoxyl group of the residue bound to the enzyme. The rate of ageing is proportional to the electron-donating capacity of the alkyl group. 2. The ageing of phosphophonylated cholinesterase cal also be demonstrated using a phrenic nerve-diaphragm preparation. The same relationship between the rate of ageing and the structure of the alkyl group was observed. 3. Ageing occurs much faster in electrically stimulated preparations than in resting preparations. This may be due to production of a more acidic environment for the enzyme at the active centre by the products of hydrolysis of the acetylcholine released by stimulation.
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000201:enzymology* / Q000294:innervation; D004355:Drug Stability; D004558:Electric Stimulation; D004789:Enzyme Activation; D007700:Kinetics; D009119:Muscle Contraction; D063065:Organophosphonates / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000502:physiology*; D013329:Structure-Activity Relationship
D063065:Organophosphonates; D009943:Organophosphorus Compounds; C022372:phosphonylated acetylcholinesterase; D000110:Acetylcholinesterase