CLONING AND EXPRESSION OF A 5'-IODOTHYRONINE DEIODINASE FROM THE LIVER OF FUNDULUS-HETEROCLITUS

Recent molecular cloning studies in mammals and amphibians have demons trated that the types I, II, and III deiodinases constitute a family o f selenoproteins of critical importance in metabolizing T-4 to active (i.e. T-3) and inactive (i.e. rT(3)) metabolites. In several tissues o f teleost fish, various deiodinase processes have been described, but the structural and functional characteristics of these enzymes and the ir relationship to the deiodinases present in higher vertebrates remai ns uncertain. Using a complementary DNA library derived from the liver of the teleost Fundulus heteroclitus, we have identified a complement ary DNA that codes for a deiodinase with functional characteristics vi rtually identical to those of the mammalian and amphibian type II deio dinase. Sequence analysis demonstrates a high degree of homology at bo th the nucleotide and predicted amino acid levels between the Fundulus clone and these previously characterized type II enzymes, including t he presence of an in-frame TGA codon that codes for selenocysteine. Th ese findings demonstrate that the deiodinase family of selenoproteins has been highly conserved during vertebrate evolution and underscores their importance in the regulation of thyroid hormone action.