Abnormalities of oxidative phosphorylation due to excess of deficiency of thyroid hormones.
ATP synthesis requires the presence of thyroid hormones that activate oxidative phosphorylation. ATP supports the energy consuming reactions such as actin-myosin interaction, calcium and sodium pump, which are essential in a normal heart function. Thyroid insufficiency depresses mitochondrial oxidation, leading to ATP depletion which can not be compensated by activated glycolysis. Glycolysis under conditions of hypoxia due to accumulation of lactate or NADPH, impairs membrane permeability and mitochondrial function, causing enzyme release and pump failure. In severe hyperthyroidism an ATP deficiency occurs by uncoupling of oxidative phosphorylation, T4 stimulating the extra-mitochondrial metabolic pathways. There is a disproportion between consumption of O2 and nutrients and ATP production. The T4--T3 excess via trace metal (magnesium, copper, zinc, iron, etc.) chelation inhibits enzyme activity which had impaired ATP synthesis. At the same time the excess of T4 by stimulating ATP-ase causes heat release and dissipation of ATP, favouring cardiothyreosis.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010725:Phosphocreatine / Q000378:metabolism; D011817:Rabbits; D013963:Thyroid Hormones / Q000494:pharmacology
D013963:Thyroid Hormones; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D006003:Glycogen