Original scientific paper

Inhibition of Human Blood Acetylcholinesterase and Butyrylcholinesterase by Ethopropazine

Vera Simeon-Rudolf ; Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000 Zagreb, Croatia
Goran Šinko ; Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000 Zagreb, Croatia
Anita Štuglin ; Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000 Zagreb, Croatia
Elsa Reiner ; Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000 Zagreb, Croatia

Abstract

Inhibition of human erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7) and serum butyrylcholinesterase (BChE; EC 3.1.1.8) by ethopropazine, 10-(2-diethylaminopropyl)phenothiazine hydrochloride, was measured with acetylthiocholine (ATCh) as substrate. Dissociation constants for the enzyme-inhibitor complexes were calculated from the effect of ATCh concentration on the apparent dissociation constants by applying non-linear regression to fit the model to experimental data. Inhibition of AChE revealed a competitive inhibition for two binding sites (K_a = 161 and K_i = 393 μmol dm-3), inhibition of the atypical BChE was non-competitive (K_i = 7.5 μmol dm-3) while that of the usual BChE was competitive (K_(I) = 0.16 μmol dm-3). At the ethopropazine concentration of 20 μmol dm-3 and the acetyl-thiocholine concentration of 1.0 mmol dm-3 (conditions used for differentiation between AChE and BChE activities), the erythrocyte AChE was 8% inhibited and the BChE phenotypes UU, UA, FF/FS, AF, AJ/AK and AA/AS between 98% and 74%.

Keywords

acetylcholinesterase; butyrylcholinesterase; ethopropazine; selective inhibition; inhibition mechanism; enzyme-inhibitor; enzyme-substrate dissociation constants

Hrčak ID:

131786

URI

https://hrcak.srce.hr/131786

Publication date:

1.2.2001.

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