5′-deiodinase

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5′-deiodinases are iodothyronine deiodinases that convert the thyroid hormone thyroxine (T4) into triiodothyronine (T3). They play a crucial role in the activation of iodothyronines . Deiodinases are selenium-dependent enzymes .

Mechanism of activation

Deiodinases activate iodothyronines by removing an iodine atom on the outer ring (5′-position). In this way, T4 is converted to T3. Similar reactions mediated by 5'-deiodinases are the conversion of T3 to 3,5-T2 or of rT3 to 3,3'-T2 .

Reactions catalyzed by deiodinases
Regulation of deiodinase activity

Types

Most vertebrates have two 5'-deiodinases that activate thyroid hormones. There is also an inactivating 5-deiodinase (type 3 deiodinase, D3).

Type localization function
Type 1 (D1) including liver and kidney Deiodination of both rings (5-deiodination and 5′-deiodination)
Type 2 (D2) Heart muscle , skeletal muscle , central nervous system , adipose tissue , thyroid , pituitary gland Outer ring deiodization (5′-deiodization)
Type 3 (D3) Fetal tissue and placenta Inner ring deiodization (5-deiodization)

Pathophysiology

Deiodinases are plastic enzymes that can be regulated by a variety of control influences. In severe general diseases, the 5′-deiodinase activity is reduced, while the activity of 5-deiodinase is increased ( non-thyroidal illness syndrome ).

Measurement of enzyme activity

In vitro , e.g. B. in cell culture experiments , the enzyme activity can be investigated by measuring the T3 formation or the iodine release under maximum substrate saturation with T4 and the required cosubstrates . In vivo , the activation of thyroid hormones can be estimated from equilibrium values ​​of T4 and T3 with the help of the T3-T4 quotient or the calculated total activity of peripheral deiodinases (G D ).

literature

  1. B. Gereben, AM Zavacki, S. Ribich, BW Kim, SA Huang, WS Simonides, A. Zeöld, AC Bianco: Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. In: Endocr Rev . 29 (7), Dec 2008, pp. 898-938. doi: 10.1210 / er.2008-0019 . PMID 18815314 .
  2. ^ National Academy of Hypothyroidism , Deiodinases.