In vitro kinetics of the mouse hepatic arginase inhibition by hexachlorophene

Abstract

Hexachlorophene (HCP) inhibited mouse hepatic arginase with a half-inhibitory concentration (I 50) of 1.3 × 10 −6 M. The enzyme-HCP interaction coefficients denoted alteration of inhibitory sites on the enzyme, depending on the concentration of HCP. The K m of hepatic arginase was 8.3 m M which was not significantly affected in the presence of HCP, whereas the V max and V max -to- K m ratios were reduced by HCP by the same factor, denoting a pure noncompetitive inhibition which was further confirmed by the finding that the inhibitor constants K i and K′ i were equal to one another and also to the I 50. The enzyme in the presence of HCP demanded higher than the normal amount of activation energy ( E a). The Mn 2+-activated arginase was less susceptible than was the Mn 2+-deficient enzyme to HCP inhibition. These findings, together with recovery studies employing bovine serum albumin, denoted that HCP may induce conformational changes on the enzyme, probably by exerting strong interactions at the noncatalytic sites of the enzyme.