Naslov
Interaction of human butyrylcholinesterase variants with bambuterol and terbutaline

Autori
Kovarik, Zrinka ; Simeon-Rudolf, Vera

Izvornik
Journal of Enzyme Inhibition and Medicinal Chemistry (1475-6366) 19 (2004), 2; 113-117

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Bambuterol; Human butyrylcholinesterase variants; Inhibition; Terbutaline

Sažetak
Bambuterol, a dimethylcarbamate, carbamoylates butyrylcholinesterase (BChE ; EC 3.1.1.8). The carbamoylated enzyme is not very stable and the final product of the two-step hydrolysis is a bronchodilator drug, terbutaline (1-(3, 5-dihydroxyphenyl)-2-t-butylaminoethanol sulphate). Both bambuterol and terbutaline inhibit BChE, but their affinities differ in human serum BChE variants (U, A, F, K and S) due to their positive charge. Bambuterol inhibition rate constants for the homozygous usual (UU), Kalow (KK), fluoride resistant (FF) or atypical (AA) variant ranged from 4.4 to 0.085 min-1μ M-1. Terbutaline showed competitive reversible inhibition for all BChE variants. The dissociation constants for UU, FF and AA homozygotes were 0.18, 0.31 and 3.3 mM, respectively. The inhibition rate or dissociation constants for heterozygotes were distributed between the respective constants for the corresponding homozygotes. A 50-fold difference in inhibition between the UU and AA enzyme might affect terbutaline release in humans. The affinity of all studied BChE variants for terbutaline was low, which suggests that terbutaline originating from bambuterol hydrolysis should not affect the hydrolysis of bambuterol by BChE.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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