Mechanism of thyroxine-mediated oxidation of reduced nicotinamide adenine dinucleotide in the peroxidase-hydrogen peroxide system

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Abstract
The oxidation of NADH by the horseradish peroxidase [EC 1.11.17] (HRP-H2O2 system is greatly increased by the addition of thyroxine [T4] or related compounds. On the basis of a study of the rate of NADH oxidation in the presence of various concentrations of T4, it is clear that T4 acts as a catalyst for NADH oxidation. Spectral changes of a HRP-H2O2 complex (compound I) indicate that T4 acts as an electron donor to both compounds I and II. The rate of electron donation from T4 is much faster than that from NADH. The HRP-H2O2 system requires 0.83 mol of O2 for the oxidation of 1 mol of NADH. Ferricytochrome c is reduced to ferrocytochrome c by the system, and causes an inhibition of O2 consumption which can be abolished by superoxide dismutase. Judging from the inhibition of O2 uptake by ferricytochrome c, about 54% of the total flux of electrons from NADH to oxygen appears to proceed by way of .**GRAPHIC**. These results suggest that the initial step of T4-mediated NADH oxidation by HRP and H2O2 is the formation of oxidized T4, a phenoxy radical, which attacks NADH to produce NAD.