Thyroxine-supported oxidation in the myeloperoxidase system.
Thyroxine and other iodothyronines (concentrations in the nanomolar range) stimulated the oxidation of NADH in the myeloperoxidase-H2O2-Cl- system. In the absence of chloride, thyroxine had only a marginal effect. This suggests that thyroxine increased the generation of chlorinating oxidants. A peroxidase-catalysed oxidation product of thyroxine, 3,5-diiodotyrosine, was inactive. Pre-incubation of thyroxine in the myeloperoxidase system showed that thyroxine was oxidized to a product capable of stimulating NADH oxidation. Reduction and alkylation of myeloperoxidase under nondenaturing conditions also increased the oxidative activity of the enzyme. It is postulated that both iodoacetamide and a thyroxine-derived oxidation product (presumably a quinone) alkylate sulphydryl groups near the active centre of myeloperoxidase making it more accessible for its substrate.
van Zyl
J M
JM
Department of Pharmacology, Faculty of Medicine, University of Stellenbosch, Tygerberg, South Africa.
van der Walt
B J
BJ
Kriegler
A
A
D000478:Alkylation; D002712:Chlorides / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism / Q000494:pharmacology*
D002712:Chlorides; D009243:NAD; D006861:Hydrogen Peroxide; D009195:Peroxidase; D013974:Thyroxine