Acetylcholinesterase plant-derived

Neurotransmitters are removed by translocation into vesicles or destroyed in enzyme-catalysed reactions. Acetylcholine must be removed from the synaptic cleft to permit repolarization and relaxation. A high affinity acetylcholinesterase (AChE) (the true or specific AChE) catalyses the hydrolysis of acetylcholine to acetate and choline. A plasma AChE (pseudo-AChE or non-specific AChE) also hydrolyses acetylcholine. A variety of plant-derived substances inhibit AChE and there is considerable interest in AChE inhibitors as potential therapies for cognition enhancement and for Alzheimer s disease. Organophosphorous compounds alkylate an active site serine on AChE and the AChE inhibition by this mechanism is the basis for the use of such compounds as insecticides (and unfortunately also as chemical warfare agents). Other synthetics with insecticidal and medical applications carbamoylate and thus inactivate AChE (Table 6.4). 

Evron, T., Geyer, B.C., Chemi, I., Muralidharan, M., Kilboume, J., Fletcher, S.P., Soreq, H., Mor, T.S. (2007a). Plant-derived human acetylcholinesterase-R provides protection from lethal organophosphate poisoning and its chronic aftermath. FASEB J. 21 2961-9. 

Itself a deadly poison derived from belladonna or other nightshade plants (see Chapter 19), atropine must be administered with great care. The organophosphate residues can be bound with oximes to release acetylcholinesterase. This is shown below for the reaction of organophosphate-bound acetylcholinesterase enzyme with pralidoxime ... 

Galanthamine also blocks acetylcholine estaase activity. One of the new applicaticms of galanthamine is in a treatment of Alzheimer s disease (AD). Moreover, this natural (and presently also synthetically driven) alkaloid can be used in decreasing negative side effects caused by applications of nondepolarizing alkaloids, for example, those of tubocurarine. Acetylcholinesterase activity is reported to depress and inhibit by lycorine and its derivatives. Lycorine is an object of therapeutic approaches to cure AD and decrease a level of esterase activity, Other alkaloids from the Amaiyllidaceae plant family are probably useful for these purposes and are being researched. 

---