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.
Doerge
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Department of Agricultural Biochemistry, University of Hawaii, Honolulu 96822.
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004563:Electrochemistry; D006418:Heme / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D007784:Lactoperoxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D006418:Heme; D006861:Hydrogen Peroxide; D007784:Lactoperoxidase; D010544:Peroxidases; D013890:Thiourea