Hydroperoxide-dependent metabolism of goitrogenic thiocarbamides by lactoperoxidase.

1. Inhibition of lactoperoxidase by thiocarbamides is consistent with a suicide mechanism whereby enzyme-catalysed S-oxygenation produces reactive intermediates which covalently modify the active site haem. 2. The reaction of thiocarbamide goitrogens with lactoperoxidase in the presence of hydroperoxides results in time-dependent and irreversible enzyme inactivation and an altered visible spectrum of the haem prosthetic group of the inactivated enzyme. 3. A mechanism of S-oxygenation for the inactivation is suggested by lactoperoxidase-catalysed formation of stable S-oxides from thioamide and organosulphur functional groups, and by a common dependence of substrate and inhibitor binding constants on their electrochemical oxidation potentials. 4. Hydroperoxide-dependent inactivation of lactoperoxidase by benzimidazoline-2-thiones occurs concomitantly to the covalent binding of stoichiometric amounts of 14C- or 35S-labelled inhibitors per mole of enzyme, and the formation of turnover products derived from the hydroperoxide cosubstrate and inhibitor.