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Iodothyronine deiodinases (DIO1, DIO2, DIO3) !

Three selenoenzymes that activate T4 to T3 or inactivate it; they decide how much active thyroid hormone each tissue gets.

Updated 2026-11-01

Key facts

  • DIO1 and DIO2 remove an outer-ring iodine (5'-deiodination): T4 → active T3. DIO3 removes an inner-ring one: T4 → reverse T3 (inactive) and T3 → T2.
  • They carry selenocysteine in the active site: they need selenium.
  • DIO1 (liver, kidney, thyroid) supplies T3 to blood and is sensitive to propylthiouracil; DIO2 (brain, pituitary, brown fat, muscle) makes T3 inside the cell.
  • About 80 % of circulating T3 is made outside the thyroid by deiodination.
  • There are no human structures in the PDB (only mouse DIO3, without ligand), so this page shows no 3D model.
Also called
Deiodinases, 5'-deiodinases
EC number
1.21.99.4
Genes
DIO1, DIO2, DIO3

Regulation

  • Hypothyroidism raises DIO2 and lowers DIO3 (protecting brain T3); hyperthyroidism does the opposite.
  • In the pituitary, DIO2 turns T4 into T3 to hold TSH back (feedback).
  • Fasting and severe illness reduce T4-to-T3 conversion and raise reverse T3.

Inhibitors and toxins

  • Propylthiouracil (DIO1)
  • Amiodarone
  • Glucocorticoids and propranolol (reduce peripheral conversion)
  • Iodinated contrast media

Clinical notes

  • In critically ill patients T3 falls and reverse T3 rises with normal TSH (low-T3 or sick euthyroid syndrome).
  • Large infant haemangiomas express a lot of DIO3 and cause consumptive hypothyroidism.
  • Brown-fat DIO2 supplies T3 for UCP1 thermogenesis in the cold.

Pathways

Test yourself

Think of the answer, then tap the question to see it.

Which deiodinase inactivates T4 by forming reverse T3?

DIO3, which removes an inner-ring iodine.

Why do deiodinases depend on selenium?

Because their active site contains selenocysteine.

Which deiodinase does propylthiouracil inhibit?

DIO1, as well as thyroid peroxidase.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: DIO1: Type I iodothyronine deiodinase (human) (UniProt, 2026); DIO2: Type II iodothyronine deiodinase (human) (UniProt, 2026); DIO3: Thyroxine 5-deiodinase (human) (UniProt, 2026); T3 test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.