c) Tg-iodinated tyrosine —» Tg-thyronines

4. The H202 Generation System

Peroxide (H202) is an obligatory electron receptor for the reactions catalyzed by TPO. In fact, the rate of generation of H202 controls the relative rates of tyrosyl iodination and coupling. As shown in Figure 6-8, two mechanisms of generation of H202 have been proposed; as yet there is no agreement on which pathway is favored. The required NADPH is derived from the pentose phosphate pathway.

5. Molecular Mechanisms of Tyrosine Iodination and Iodotyrosine Coupling

The enzymatic production of iodotyrosines on thy-roglobulin (phase A) and their subsequent coupling to generate thryoglobulin-bound thyronines (phase B) are both mediated by the enzyme thyroid peroxidase (TPO). The precise details of this series of complex enzymatic transformations are not yet available. How ever, Figure 6-9 presents a schematic pathway that invokes the involvement of three participants designated compounds I, II, and III; compounds I and II are believed to be conjugates with TPO (see Figure 6-9), but their precise structures are not yet known.

In phase B, TPO mediates a concerted succession of three steps, which results in the formation of equimolar amounts of thyronine hormone and dehydroalanine within the polypeptide chain of thyroglobulin (see Figure 6-10). The locations of the preferred hormonogenic sites on Tg for the generation of thyronine are indicated in Figure 6-5.

One of the major physiological controls of the formation of monoiodotyrosine formation is the dietary iodide supply. In the absence of ample dietary iodine, the iodotyrosine:iodothyronine and MIT:DIT ratios increase due to poor iodination of thyroglobulin.

It has also been observed that the iodination of thyroglobulin is inhibited by excess iodide; this is known

NADPH oxidase apical membrane

NADPH oxidase

0 0

Post a comment