Interaction of anions with rat liver arginase: specific inhibitory effects of fluoride.
The inhibitory effects of anions, such as N(3)(-), NO(2)(-), BO(4)(3-), SCN(-), CH(3)COO(-), SO(4)(2-), ClO(4)(-), H(2)PO(4)(-), CN(-), I(-), Br(-), Cl(-) and F(-), on the hydrolysis of L-arginine (L-Arg) by rat liver arginase (RLA) have been studied. From all these anions, only F(-) exhibited a clear inhibitory effect at the mM level. Inhibition of RLA by F(-) is reversible and uncompetitive towards L-Arg binding with a K(i) value of 1.3+/-0.5 mM at pH 7.4. This effect is dependent on pH as the IC(50) value of F(-) towards RLA increases from 1.2 to 19 mM when increasing the pH from 7 to 10. Another specific inhibitor of RLA, N(omega)-hydroxy-L-nor-arginine (nor-NOHA), that has been recently shown to bind to RLA as a bridging ligand of its (Mn(II))(2) cluster, exhibits some similarities with F(-) in its inhibitory effects (identical pH dependence). It is thus tempting to propose that the inhibitory effects of F(-) could be due to its binding as a bridging ligand of the RLA (Mn(II))(2) cluster. However, further studies are required to determine the modes of interaction of F(-) with RLA.
Pethe
Stéphanie
S
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601, Université René Descartes, 45 Rue des Saints-Pères, 75270 Paris Cedex 06, France.
Boucher
Jean Luc
JL
Mansuy
Daniel
D
D000818:Animals; D000838:Anions; D001119:Arginase / Q000037:antagonists & inhibitors*; D001120:Arginine / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008958:Models, Molecular; D051381:Rats; D017207:Rats, Sprague-Dawley
D000838:Anions; D004791:Enzyme Inhibitors; D001120:Arginine; D001119:Arginase; D005459:Fluorides