Molecular structure and potency of inhibition

Introducing a methyl group into the ring, as in fenitrothion, increases the hydrophobicity and increases the affinity to the active site of the enzyme, but reduces its reaction velocity. The net result on AChE is therefore much the same. However, the changes make it less toxic to mammals, while the 

The next three compounds are carbamates. Eserine is important because it is a very strong inhibitor of all cholinesterases and is used to verify that an esterase is a cholinesterase. Carbaryl also has a very high affinity to some cholinesterases, but a very low affinity to others. It is an important insecticide. Aldicarb was made to resemble acetylcholine. In spite of this, its affinity is very low (high Kd), but due to its high reaction rate (k+2 value), aldicarb is very toxic. 

The half-lives and the corresponding k+3 values are dependent on the structure of, and therefore the source of, the enzyme and the structure of the group attached to the serine residue of the enzyme. Note the tremendous difference between the acetylated enzyme and the enzyme s phosphate and carbamate adducts. The half-lives are generally lower for the carbamylated enzymes but long enough to cause serious poisoning. 

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