Mechanism of thyroxine-mediated oxidation of reduced nicotinamide adenine dinucleotide in peroxidase-H2O2 system.
The oxidation of reduced nicotinamide adenine dinucleotide (NADH) by the horseradish peroxidase (HRP)-H2O2 system is greatly increased by the addition of thyroxine or related compounds. On the basis of a study of the rate of NADH oxidation in the presence of various concentrations of thyroxine, it is clear that thyroxine acts as a catalyst for NADH oxidation. Spectral changes of a HRP-H2O2 complex (compound I) indicate that thyroxine acts as an electron donor to both compounds I and II. The rate of electron donation from thyroxine 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 O2-. These results suggest that the initial step of thyroxine-mediated NADH oxidation by HRP and H2O2 is the formation of oxidized thyroxine, a phenoxy radical, which attacks NADH to produce NAD.
D003574:Cytochrome c Group / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism*; D007700:Kinetics; D009243:NAD / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010544:Peroxidases / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013963:Thyroid Hormones / Q000494:pharmacology; D013974:Thyroxine / Q000494:pharmacology*
D003574:Cytochrome c Group; D013963:Thyroid Hormones; D009243:NAD; D006735:Horseradish Peroxidase; D010544:Peroxidases; D013482:Superoxide Dismutase; D013974:Thyroxine