Conversion of T3 and rT3 to 3,3'-T2: pH dependency.

In the extrathyroidal deiodination of T4 the importance of T3 and rT3 for the peripheral action of thyroid hormones is well documented. With the development of a specific radioimmunoassay for 3,3'-T2, a deiodination product of both T3 and rT3, we were able to characterize these subsequent enzymatic reactions as well as the degradation of 3,3'-T2 in rat liver homogenate. It was found that the reaction T3 leads to 3,3'-T2 is slow compared to the conversion of T4 to T3. The pH activity profile shows a peak at 8.4. The reaction rT3 leads to 3,3'-T2 is very fast, with an apparent KM of 4 x 10(-7) M. The reaction velocity is significantly higher in acid than in alkaline pH. The deiodination of 3,3'-T2 is also faster in the acid than in the alkaline range. It is concluded that the outer ring of T4 is more readily deiodinated in acid and the inner ring in alkaline media, and that 3,3'-T2 is mainly degraded to 3-T1. In the acid pH range T3 may accumulate and in the alkaline range rT3 by the pH characteristics of these ractions. Therefore small shifts in pH can enhance the potent inhibitory action of rT3 on the 5'-deiodination of T4 adding another mechanism to the peripheral regulation of thyroid hormone activity.