Naslov
Inhibition of cholinesterases by bambuterol and haloxon

Autori
Štuglin, Anita ; Latas, Tatjana ; Kovarik, Zrinka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
1st Croatian Congress on Molecular Life Sciences with International Participation, Opatija, Book of Abstracts / Dumić, Jerka et al. - Zagreb : Farmaceutsko-biokemijski fakultet Sveučilišta u Zagrebu, 2002

Skup
1st Croatian Congress on Molecular Life Sciences with International Participation

Mjesto i datum
Opatija, Hrvatska, 09.06.2002. - 13.06.2002

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Sažetak
Carbamates and organophosphorus compounds are potent inhibitors of serine esterases, butyrylcholinesterase (EC 3.1.1.8) and acetylcholinesterase (EC 3.1.1.7). To compare interaction of mouse acetylcholinesterase and butyrylcholinesterase, as well as those of butyrylcholinesterase from mouse, human, or horse, inhibition by bambuterol (5[2-(tert-butylamino)-1-hydroxyethyl]-m-phenylene-bis(dimethylcarbamate) hydrochloride) and haloxon (Di-(2-chloroethyl)-3-chloro-4-methyl-coumarin-7-yl phosphate) was performed. The time course of inhibition was followed by measuring the enzyme activity using spectrophotometric method, and the rate constants inhibition were calculated. Both inhibitors were faster inhibitor of butyrylcholinesterase from all studied species than of mouse acetylcholinesterase. Mouse butyrylcholinesterase is 16 000-times faster inhibited by bambuterol (ki (bambuterol)=5.7 x 106 min-1M-1) and 90-times by haloxon (ki (haloxon)=3.9 x 107 min-1M-1) than mouse acetylcholinesterase. Six aliphatic amino acids in active gorge of butyrylcholinesterase, which are in acetylcholinesterase substitute for six aromatic amino acids, provide better approach of bambuterol and haloxon to the catalytic centre of the enzyme resulting by more efficient inhibition of butyrylcholinesterase in comparison to acetylcholinesterase. The rate inhibition constants of horse butyrylcholinesterase differ about 25– times by bambuterol and about 4– times by haloxon from the rates of mouse or human butyrylcholinesterase. Similar inhibition rates of mouse and human butyrylcholinesterase are dictated by higher amino acid sequence homology than that of horse butyrylcholinesterase. Primarily structure of horse butyrylcholinesterase differs from the sequences of the other two species in six amino acids.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA