The deiodinase family of selenoproteins

Abstract

The realization some forty years ago that several iodothyronine compounds are present in the circulation suggested that deiodination occurs in various tissues. Subsequently, deiodination was indeed documented in in vivo studies. Later, using in vitro assay techniques, three deiodinase processes, termed types 1, 2 and 3, were defined that differed in terms of tissue distribution, reaction kinetics, efficiency of substrate utilization and sensitivity to inhibitors. Although purification of the deiodinase enzymes has continued to be problematic, recent molecular cloning studies have identified cDNAs for these three deiodinase isoforms from multiple species. These cDNAs have provided important insights into the structural characteristics of this family of enzymes. Foremost among the structural features has been the demonstration that all three deiodinase isoforms contain at their active site the uncommon amino acid selenocysteine which is of critical importance to their catalytic activity. The availability of cDNAs for these enzymes provides important reagents for pursuing additional studies aimed at defining their biochemical features and roles in thyroid hormone economy.