title: A nonselenoprotein from amphioxus deiodinates triac but not T3: is triac the primordial bioactive thyroid hormone?
abstract: Thyroid hormone (TH) is important for metamorphosis in many species, including the cephalochordate Branchiostoma floridae, a marine invertebrate (amphioxus) living in warmer coastal areas. Branchiostoma expresses a TH receptor, which is activated by 3,3',5-triiodothyroacetic acid (TA(3)) but not by T(3). The Branchiostoma genome also contains multiple genes coding for proteins homologous to iodothyronine deiodinases in vertebrates, selenoproteins catalyzing the activation or inactivation of TH. Three Branchiostoma deiodinases have been cloned: two have a catalytic Sec, and one, bfDy, has a Cys residue. We have studied the catalytic properties of bfDy in transfected COS1 cells by HPLC analysis of reactions with (125)I-labeled substrates and dithiothreitol as cofactor. We could not detect deiodination of T(4), T(3), or rT(3) by bfDy but observed rapid and selective inner ring deiodination (inactivation) of TA(3) and 3,3',5,5'-tetraiodothyroacetic acid (TA(4)). Deiodination of TA(3) by bfDy was optimal at 25 C and 10 mm dithiothreitol. bfDy was extremely labile at 37 C, showing a half-life of less than 2 min, in contrast with a half-life of more than 60 min at 25 C. Deiodination of labeled TA(3) was inhibited dose dependently by unlabeled TA(3)≈TA(4)>T(4)≈T(3). Michaelis-Menten analysis yielded Michaelis-Menten constant values of 6.8 and 68 nm and maximum velocity values of 1.4 and 5.4 pmol/min·mg protein for TA(3) and TA(4), respectively. bfDy was not inhibited by propylthiouracil and iodoacetate and only weakly by goldthioglucose and iopanoic acid. In conclusion, we demonstrate rapid inactivation of TA(3) and TA(4) but not of T(3) and T(4) by the first reported natural nonselenodeiodinase. Our findings support the hypothesis that TA(3) is a primordial bioactive TH.
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Klootwijk
authors.forename: Edith C H
authors.initials: EC
authors.lastname: Friesema
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002816:Chordata, Nonvertebrate / Q000235:genetics*; D004229:Dithiothreitol / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D013974:Thyroxine / Q000031:analogs & derivatives / Q000378:metabolism; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid; D007453:Iodide Peroxidase; C011126:tetraiodothyroacetic acid; D013974:Thyroxine; D004229:Dithiothreitol