Abstract
ALTHOUGHthyroxine (3,5,3',5'-tetraiodothyronine, T4) is the principal secretory product of the vertebrate thyroid, its essential metabolic and developmental effects are all mediated by 3,5,3'-triiodothyronine (T3), which is produced from the prohormone by 5'-deiodination. The type-I iodothyronine deiodinase, a thiol-requiring propylthiouracil-sensitive oxidoreductase, is found mainly in liver and kidney and provides most of the circulating T31 but so far this enzyme has not been purified. Using expression cloning in the Xenopus oocyte, we have isolated a 2.1-kilobase complementary DNA for this deiodinase from a rat liver cDNA library. The kinetic properties of the protein expressed in transient assay systems, the tissue distribution of the messenger RNA, and its changes with thyroid status, all confirm its identity. We find that the mRNA for this enzyme contains a UGA codon for selenocysteine which is necessary for maximal enzyme activity. This explains why conversion of T4 to T3is impaired in experimental selenium deficiency2–6 and identifies an essential role for this trace element in thyroid hormone action.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Larsen, P. R., Silva, J. E. & Kaplan, M. M. Endocr. Rev. 2, 87–102 (1981).
Beckett, G. J., Beddòws, S. E., Morrice, P. C., Nicol, F. & Arthur, J. R. Biochem. J. 248, 443–447 (1987).
Arthur, J. R., Morrice, P. C. & Beckett, G. J. Res. Vet. Sci. 45, 122–123 (1988).
Beckett, G. J., MacDougall, D. A., Nicol, F. & Arthur, J. R. Biochem. J. 259, 887–892 (1989).
Arthur, J. R., Nicol, F., Hutchinson, A. R. & Beckett, G. J. J. inorg. Biochem. 39, 101–108 (1990).
Arthur, J. R., Nicol, F., Rae, P. W. H. & Beckett, G. J. Clin. Chem. Enzym. Commun. 3, 209–214 (1990).
Berry, M. J., Kates, A.-L. & Larsen, P. R. Molec. Endocr. 4, 743–748 (1990).
St Germain, D. L. & Morganelli, C. M. J. biol. Chem. 264, 3054–3056 (1989).
Aruffo, A. & Seed, B. Proc. natn. Acad. Sci. U.S.A. 84, 8573–8577 (1987).
Brent, G. A. et al. Molec. Endocr. 3, 1996–2004.
Leonard, J. L. & Visser, T. J. in Thyroid Hormone Metabolism (ed. Hennemann, G.) 189–229 (Dekker, New York, 1986).
Chambers, I. et al. EMBO J. 5, 1221–1227 (1986).
Mullenbach, G. T. et al. Protein Engng 2, 239–246 (1988).
Zinoni, F., Birkmann, A., Stadtman, T. C. & Bock, A. Proc. natn. Acad. Sci. U.S.A. 83, 4650–4654 (1986).
Menon, N. K., Peck, H. D. Jr, LeGall, J. & Przybyla, A. E. J. Bact. 169, 5401–5407 (1987).
Ishida, K., Morino, T., Takagi, K. & Sukenaga, Y. Nucleic Acids Res. 15, 10051 (1987).
Lee, B. J. et al. Molec. cell. Biol. 10, 1940–1949 (1990).
Behne, D., Hilmert, H., Scheid, S., Gessner, H. & Elger, W. Biochim. biophys. Acta 966, 12–21 (1988).
Behne, D., Scheid, S., Kyriakopoulos, A. & Hilmert, H. Biochim. biophys. Acta 1033, 219–225 (1990).
Kohrle, J., Rasmussen, U., Rokos, H., Leonard, J. L. & Hesch, R. D. J. biol. Chem. 265, 6146–6154 (1990).
Schoenmakers, C. H. H., Pigmans, I. G. A. J., Hawkins, H. C., Freedman, R. B. & Visser, T. J. Biochem. biophys. Res. Commun. 162, 857–866 (1989).
Forstrom, J. W., Zakowski, J. J. & Tappel, A. L. Biochemistry 17, 2639–2644 (1978).
Chaudiere, J. & Tappel, A. L. J. inorg. Biochem. 20, 313–325 (1984).
Tappel, A. L. Curr. Top. Cell Reg. 24, 87–97 (1984).
Visser, T. J., Frank, S. & Leonard, J. L. Molec. cell. Endocr. 33, 321–327 (1983).
Devereux, J., Haeberli, P. & Smithies, O. Nucleic Acids Res. 12, 387–395 (1984).
Boada, R. J., Campbell, D. A. & Chopra, I. J. Biochem. biophys. Res. Commun. 155, 1297–1304 (1988).
Oppenheimer, J. H., Schwartz, H. L. & Surks, M. I. J. clin. Invest. 51, 2493–2497 (1972).
Frumess, R. D. & Larsen, P. R. Metabolism 24, 547–554 (1975).
Gubler, U. & Hoffman, B. Gene 25, 263–269 (1983).
Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Berry, M., Banu, L. & Larsen, P. Type I iodothyronine deiodinase is a selenocysteine-containing enzyme. Nature 349, 438–440 (1991). https://doi.org/10.1038/349438a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/349438a0
This article is cited by
-
Protective Effects of Selenium and Zinc Against Nickel Chloride–Induced Hormonal Changes and Oxidative Damage in Thyroid of Pregnant Rats
Biological Trace Element Research (2022)
-
Construction of starch-based bionic glutathione peroxidase and its catalytic mechanism
Chemical Papers (2022)
-
Crystal Structures of a New Polymorph of N-tert-butyl-2-thioimidazole, and Its 1,4-Diiodotetrafluorobenzene, Tetraiodoethylene, and Iodine Cocrystals
Journal of Chemical Crystallography (2022)
-
Effect of organic and inorganic dietary selenium supplementation on gene expression in oviduct tissues and Selenoproteins gene expression in Lohman Brown-classic laying hens
BMC Veterinary Research (2021)
-
Protective effects of selenium and zinc against potassium dichromate–induced thyroid disruption, oxidative stress, and DNA damage in pregnant Wistar rats
Environmental Science and Pollution Research (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.