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 3COO −, SO 4 2−, ClO 4 −, H 2PO 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 ω-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.