Thyroxine-Supported Oxidation in the Myeloperoxidase System

Abstract

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.

Myeloperoxidase: friend and foe

“…Although thyroxine can substitute for the halide in the MPO-H 2 O 2 -halide antimicrobial system [69], throxine is deiodinated under these conditions [204,205], raising the possibility that the released iodide may be the required microbicidal component. The thyroid hormones have, however, been reported to stimulate the generation of chlorinating oxidants by the MPO-H 2 O 2 -chloride system [383,384]. Impaired thyroid hormone or estrogen response has not been noted in patients with MPO deficiency, suggesting that the phenolic hormones do not require MPO for their action.…”

Thyroid Hormone Supplementation in Sepsis: An Experimental Study

“…39 However, T4 was found to be ineffective in the absence of Cl Ϫ , thus suggesting that the hormone stimulated HOCl generation. 41,42 It has been reported by Durmuş et al 43 that the elevation in the intraperitoneal concentration of the bacteria caused thyroid hormones to decline in experimentally developed sepsis.…”

“…3 Van Zyl et al 41,42 showed that leukocytes concentrated iodine. The preincubation of thyroxine in the myeloperoxidase system showed thyroxine to be oxidized to a product capable of stimulating NADH oxidation.…”

“…The antimicrobial activity of myeloperoxidase has been shown to be stimulated with alcylation of the -SH groups at an active site which makes it more convenient for the enzyme to bind to the substrate by the oxidation products of the thyroid hormones. 41,42 The criteria for the prognosis of sepsis were clearly defined by Bone et al 15 A leukocyte count above 12 000/mm 3 or below 4 000/mm 3 and more than 10% of the band form in the blood smear were considered to be important criteria for infection, and neutropenia was a factor leading to a poor prognosis. 15 A low number of leukocytes and the lower rate of neutropenia in the T3-and T4-supplemented groups led us to think that thyroid hormone supplementation could prevent leukocytosis in an experimental sepsis model.…”