Iodothyronine Deiodinases: structure-function analysis and their role in the regulation of thyroid hormone levels
Year: 2005
Type: dissertation
Abstract: Thyroid hormone is important for energy metabolism, the metabolism of nutrients, \ninorganic ion fluxes and thermogenesis. Thyroid hormone is also essential for stimulation of \ngrowth and development of various tissues at critical periods including the central nervous \nsystem. Whereas in the adult thyroid hormone deficiency or excess may lead to an extensive \narray of clinical manifestations which are usually reversible with proper treatment, prolonged \ndeficiency of thyroid hormones during development usually leads to irreversible damage, \ndepending on specific timing of onset and duration of thyroid hormone deficiency. Therefore, \nthyroid hormone levels are strictly regulated and thyroid hormone metabolism is a key \nprocess in the regulation of thyroid hormone homeostasis. Deiodination is the most important \nmetabolic pathway. Thyroid hormone is produced in the thyroid mainly as the biologically \ninactive precursor T4. In humans, only about 20% of the receptor active T3 is produced by the \nthyroid; most circulating T3 is derived from ORD of T4 by D1 activity in the peripheral \ntissues, mainly in the liver. Local T3, however, is derived from ORD of T4 by D2 activity. \nTherefore, ORD is regarded as an activating step. Since IRD of T4 and T3 results in the \nbiological inactive compounds rT3 and T2, respectively, IRD is regarded as an inactivating \nstep. Other metabolic pathways for iodothyronines are glucuronidation or sulfation of the \nphenol hydroxyl group and, to a minor extent, ether bond cleavage and oxidative deamination \nof the alanine side chain.
Author: F. W. J. S. Wassen
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2129446902