Deiodination of thyroid hormones by the perfused rat liver

1. An investigation has been made into the deiodination of thyroid hormones by the perfused rat liver. The hormones were labelled with (125)I in the phenolic ring and the rate of deiodination was estimated by measuring the release of radio-iodide into the perfusate.2. At tracer concentrations, 0.98% of the liver thyroxine is deiodinated/5 min. The deiodination of tri-iodothyronine is considerably faster, 3.3%/5 min.3. Deiodination is very sensitive to changes in temperature.4. The reaction shows saturation kinetics typical of many enzymes, the reciprocal of the rate of deiodination being proportional to the reciprocal of the hormone concentration in the tissue. The maximum rate of deiodination of each hormone is about 1.5 mug/min for a whole liver preparation weighing 16 g.5. Tri-iodothyronine inhibits thyroxine deiodination and vice versa, suggesting that a single enzyme is responsible for both reactions.6. Propyl thiouracil (PTU) at high concentrations inhibits the deiodination of both hormones.7. An abnormally high rate of deiodination is associated with the actual injection of hormone into the preparation. This suggests that only the free (unbound) hormone in the tissue is directly available to the deiodinating enzyme.8. About half of the whole body deiodination of thyroxine is relatively insensitive to PTU. It is suggested that most of this type of deiodination is performed in the liver and that the process is one of inactivation.