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.