Iodothyronine Deiodinase - Activation and Inactivation

Activation and Inactivation

In tissues, deiodinases can either activate or inactivate thyroid hormones:

• Activation occurs by conversion of the prohormone thyroxine (T₄) to the active hormone triiodothyronine (T₃) through the removal of an iodine atom on the outer ring.
• Inactivation of thyroid hormones occurs by removal of an iodine atom on the inner ring, which converts thyroxine to the inactive reverse triiodothyronine (rT₃), or which converts the active triiodothyronine to the inactive diiodothyronine (T₂).

The major part of thyroxine deiodination occurs within the cells.

Dionidase 2 activity can be regulated by ubiquitination:

• The covalent attachment of ubiquitin inactivates D2 by disrupting dimerization and targets it to degradation in the proteosome.
• Deubiquitination removing ubiquitin from D2 restores its activity and prevents proteosomal degradation.
• The Hedgehog cascade acts to increase D2 ubiquitination through WSB1 activity, decreasing D2 activity.

D-propranolol inhibits Thyroxine deiodinase, thereby blocking the conversion of T4 to T3, providing some though minimal therapeutic effect.