The deiodination of thyroid hormone in rat liver

As mentioned in the preceding paragraphs, enzymatic deiodination of T4 is the most important route for the production of the biologically active thyroid hormone, T3• The liver is regarded as the principal site for the peripheral production of T3. Besides deiodination the liver is also most active in the conjugation of the different iodothyronines with either glucuronic acid or sulfuric acid. Chapter II deals with a review of recent literature concerning cellular uptake and enzymatic deiodination of iodochyronines from experiments with cultured rat hepatocytes or subcellular. fractions. The regulation and nature of the enzymatic deiodination in the liver will be compared with deiodinases found in other tissues. In order to gain more insight in the mechanism of enzymatic deiodination, attempts have been made to purify the deiodinating enzyme of rat liver and kidneys. Our efforts towards deiodinase purification will be discussed in conjunction with data available from the literature. Finally, some remarks will be made concerning the importance of the liver in thyroid hormone metabolism. The following chapters describe investigations related to the mechanism of rat liver iodothyronine deiodinase. Chapters III and IV concern the development of convenient methods for the chemical synthesis of iodothyronine sulfate esters and sulfamates, and the subsequent study of the deiodination of these compounds, especially T4 sulfate ester. The chemical modification of the iodothyronine deiodinase by diethylpyrocarbonate or photo-oxidation with Rose Bengal is reported in chapter v. These results strongly suggest the presence of an active site histidine residue. Chapter VI describes the use of N-bromoacetyl-T3 as an affinity label for the deiodinase, while chapters VII and VLII deal with the partial purification of the enzyme from rat liver microsomal fraction. Basic knowledge of the deiodinating enzymes will help us to understand the alterations of serum iodothyronine concentrations in health and disease.