Iodothyronine Deiodinases: structure-function analysis and their role in the regulation of thyroid hormone levels
(Jodothyronine Dejodases: structure-functie analyse en hun rol in de regulatie van schildklierhormoon spiegels)
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Thyroid hormone is important for energy metabolism, the metabolism of nutrients, inorganic ion fluxes and thermogenesis. Thyroid hormone is also essential for stimulation of growth and development of various tissues at critical periods including the central nervous system. Whereas in the adult thyroid hormone deficiency or excess may lead to an extensive array of clinical manifestations which are usually reversible with proper treatment, prolonged deficiency of thyroid hormones during development usually leads to irreversible damage, depending on specific timing of onset and duration of thyroid hormone deficiency. Therefore, thyroid hormone levels are strictly regulated and thyroid hormone metabolism is a key process in the regulation of thyroid hormone homeostasis. Deiodination is the most important metabolic pathway. Thyroid hormone is produced in the thyroid mainly as the biologically inactive precursor T4. In humans, only about 20% of the receptor active T3 is produced by the thyroid; most circulating T3 is derived from ORD of T4 by D1 activity in the peripheral tissues, mainly in the liver. Local T3, however, is derived from ORD of T4 by D2 activity. Therefore, ORD is regarded as an activating step. Since IRD of T4 and T3 results in the biological inactive compounds rT3 and T2, respectively, IRD is regarded as an inactivating step. Other metabolic pathways for iodothyronines are glucuronidation or sulfation of the phenol hydroxyl group and, to a minor extent, ether bond cleavage and oxidative deamination of the alanine side chain.
- heart failure
- thyroid hormone