A nonselenoprotein from amphioxus deiodinates triac but not T3: Is triac the primordial bioactive thyroid hormone?
Thyroidhormone (TH) is important for metamorphosis inmanyspecies, 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 (TA3) but not by T3. 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 with125I-labeled substrates and dithiothreitol as cofactor.Wecould not detect deiodination of T4, T3, or rT3by bfDy but observed rapid and selective inner ring deiodination (inactivation) of TA3and 3,3′,5,5′- tetraiodothyroacetic acid (TA4). Deiodination of TA3by 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 TA3was inhibited dose dependently by unlabeled TA3≈TA4>T4≈T3. 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 TA3and TA4, respectively. bfDy was not inhibited by propylthiouracil and iodoacetate and only weakly by goldthioglucose and iopanoic acid. In conclusion, we demonstrate rapid inactivation of TA3and TA4but not of T3and T4by the first reported natural nonselenodeiodinase. Our findings support the hypothesis that TA3is a primordial bioactive TH.
|Persistent URL||dx.doi.org/10.1210/en.2010-1408, hdl.handle.net/1765/31349|
Klootwijk, W., Friesema, E.C.H., & Visser, T.J.. (2011). A nonselenoprotein from amphioxus deiodinates triac but not T3: Is triac the primordial bioactive thyroid hormone?. Endocrinology, 152(8), 3259–3267. doi:10.1210/en.2010-1408