title: Iodothyronine deiodinase structure and function: from ascidians to humans.
abstract: Iodothyronine deiodinases are important mediators of thyroid hormone (TH) action. They are present in tissues throughout the body where they catalyse 3,5,3'-triiodothyronine (T(3)) production and degradation via, respectively, outer and inner ring deiodination. Three different types of iodothyronine deiodinases (D1, D2 and D3) have been identified in vertebrates from fish to mammals. They share several common characteristics, including a selenocysteine residue in their catalytic centre, but show also some type-specific differences. These specific characteristics seem very well conserved for D2 and D3, while D1 shows more evolutionary diversity related to its Km, 6-n-propyl-2-thiouracil sensitivity and dependence on dithiothreitol as a cofactor in vitro. The three deiodinase types have an impact on systemic T(3) levels and they all contribute directly or indirectly to intracellular T(3) availability in different tissues. The relative contribution of each of them, however, varies amongst species, developmental stages and tissues. This is especially true for amphibians, where the impact of D1 may be minimal. D2 and D3 expression and activity respond to thyroid status in an opposite and conserved way, while the response of D1 is variable, especially in fish. Recently, a number of deiodinases have been cloned from lower chordates. Both urochordates and cephalochordates possess selenodeiodinases, although they cannot be classified in one of the three vertebrate types. In addition, the cephalochordate amphioxus also expresses a non-selenodeiodinase. Finally, deiodinase-like sequences have been identified in the genome of non-deuterostome organisms, suggesting that deiodination of externally derived THs may even be functionally relevant in a wide variety of invertebrates.
authors: Animal Physiology and Neurobiology Section, Department of Biology, Laboratory of Comparative Endocrinology, KU Leuven, Leuven, Belgium. veerle.darras@bio.kuleuven.be
authors: Veerle M
authors: VM
authors: Darras
authors: Stijn L J
authors: SL
authors: Van Herck
mesh_terms: D000818:Animals; D005075:Biological Evolution; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D014644:Genetic Variation; D006801:Humans; D007453:Iodide Peroxidase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D007453:Iodide Peroxidase