Inhibition of human serum arylesterase by metal chlorides.
The inhibition of arylesterase (paraoxonase, EC 3.1.8.1) by metal chlorides was studied with both pooled human serum (A phenotype) and purified enzyme, using phenyl acetate as substrate. Inhibition data were analysed with the Hill equation. Results obtained with whole serum and purified enzyme were very similar. On the basis of the Hill coefficient, n(H), three groups of inhibitors were distinguished: (1) Cu(2+) and Hg(2+) for which n(H)=1, suggesting a single binding site (probably the free cysteine at position 283); these metals were mixed inhibitors, with more affinity for the free enzyme than for the enzyme-substrate complex; (2) Mn(2+), Co(2+), Ni(2+), Zn(2+), and Cd(2+) for which n(H)>1, suggesting several cooperative binding sites; (3) La(3+), for which n(H)<1. Within groups (1) and (2) the inhibiting potency followed the order of the periodic table. For the 3d elements the inhibiting order followed the Irving-Williams series, with the classical exception of Cu(2+). Only Zn(2+) was inhibitory at its physiological concentration.
Debord
Jean
J
Service de Pharmacologie-Toxicologie, Hôpital Dupuytren, 2 Avenue Martin Luther King, 87042, Limoges, France. debord.jean@wanadoo.fr
Bollinger
Jean-Claude
JC
Merle
Louis
L
Dantoine
Thierry
T
D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000097:blood; D002712:Chlorides / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics
D002712:Chlorides; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase