engleski

Inhibition of acetylcholinesterase (AChE ; E.C. 3.1.1.7) and butyrylcholinesterase (BChE ; E.C. 3.1.1.8) by terbutaline

Terbutaline is the leaving group in the hydrolysis of the bis-dimethylcarbamate ester bambuterol. The latter compound, being used as a bronchodilatator in humans, is hydrolysed by serum BChE. The reversible inhibition of cholinesterases by terbutaline was followed by measuring the enzyme activity with acetylthiocholine. The recombinant mouse enzymes BChE w.t., AChE w.t., and F297I and Y337A mutants of AChE were studied. The enzyme/inhibitor dissociation constants for binding to the catalytic and/or peripheral site of the enzymes were evaluated from the competition between terbutaline and acetylthiocholine. The terbutaline inhibition of BChE w.t. is consistent with the assumption that terbutaline binds to the catalytic and an allosteric site on the enzyme. The inhibition of AChE and mutants reveals binding of terbutaline to the active site only. Terbutaline has an affnity about 6 times greater for the active site of BChE than for that of AChE. The substitution of the choline binding site tyrosine337 for alanine results in 12 times higher affinity of AChE for terbutaline. However, the substitution of the acyl pocket amino acid phenylalanine297 with isoleucine does not alter the terbutaline-AChE dissociation constant. This observation suggests that terbutaline binding to the AChE active site depends on tyrosine337 rather than on phenylalanine297.

nije evidentirano

nije evidentirano