Acetylcholinesterase, activation volume

The parameter B2 is chosen for this project in order to gain some insight into possible consequences of varying the capability of the acetylcholinesterase to hydrolyze the neurotransmitter. Imbalances in this capability give rise to devastating diseases such as Alzheimer s and Parkinson s. The enzyme activity is included in the grouped parameter B2, which includes the maximum reaction velocity in reaction 2. The parameter B2 itself includes the enzyme activity together with three constants for the enzyme system, namely the concentration of acetylcholinesterase in compartment (II), the volume V2 of compartment (II), and the flow rate q. 

Ing (39) noted that the potencies of acetylcholine analogs containing charged atoms other than nitrogen (phosphorus, arsenic, sulfur) are in inverse order to the volumes occupied by these atoms. The carbon isostere (8) of acetylcholine exhibits no cholinergic activity, but it is an excellent substrate for acetylcholinesterase (42). Studies of the role of nitrogen substituents in the acetylcholine molecule indicate that the N,N,N-trimethy quaternary... 

Gisiger, V., Belisle, M., and Gardiner, P.F., Acetylcholinesterase adaptation to voluntary wheel running is proportional to the volume of activity in fast, but not slow, rat hind limb muscles, Eur. J. NeuroscL, 6, 673, 1994. 

On this basis, in cases where the electronic effect is important for a molecule s behavior, the interposition of a vinyl group or an aromatic group between the two groups responsible for this effect, can yield compounds that maintain the desired activity, provided of course that this does not interfere with other features essential for interaction, such as the molecule s shape and volume. An example from biological activity would be the vinyl homologue of acetylcholine that, in contrast to the natural substrate acetylcholine, is not a substrate of the enzyme acetylcholinesterase and therefore does not undergo hydrolysis. 

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