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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# 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](https://www.enzyme-database.org/query.php?ec=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

- [Thyroid hormone synthesis](https://durgical.com/en/biochemistry/pathways/thyroid-hormone-synthesis/)

## Related conditions

- [Hypothyroidism](https://durgical.com/en/conditions/hypothyroidism/)
- [Graves disease (hyperthyroidism)](https://durgical.com/en/conditions/graves-disease/)

## Related

- [Thyroxine (T4)](https://durgical.com/en/biochemistry/molecules/thyroxine/)
- [Triiodothyronine (T3)](https://durgical.com/en/biochemistry/molecules/triiodothyronine/)
- [Thyroid peroxidase (TPO)](https://durgical.com/en/biochemistry/enzymes/thyroid-peroxidase/)
- [Selenium](https://durgical.com/en/biochemistry/topics/selenium/)
- [UCP1 (thermogenin)](https://durgical.com/en/biochemistry/enzymes/ucp1/)

## 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)](https://www.uniprot.org/uniprotkb/P49895/entry) (UniProt, 2026); [DIO2: Type II iodothyronine deiodinase (human)](https://www.uniprot.org/uniprotkb/Q92813/entry) (UniProt, 2026); [DIO3: Thyroxine 5-deiodinase (human)](https://www.uniprot.org/uniprotkb/P55073/entry) (UniProt, 2026); [T3 test: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003687.htm) (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.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/iodothyronine-deiodinases/