Which amino acids contain iodine? A deep dive into thyroid hormone synthesis

Thyroxine (T4), a key thyroid hormone, is a derivative of the amino acid tyrosine and famously contains four iodine atoms. This process reveals which amino acids contain iodine, highlighting how the body utilizes a single amino acid to produce crucial metabolic regulators.

Quick Summary

The amino acid tyrosine is modified with iodine to form monoiodotyrosine (MIT) and diiodotyrosine (DIT) during the synthesis of thyroid hormones like T4 and T3.

Key Points

• Tyrosine's Primary Role: The amino acid tyrosine is the precursor that is directly iodinated to create iodine-containing compounds crucial for thyroid hormone synthesis.

• MIT and DIT as Intermediates: Monoiodotyrosine (MIT) and diiodotyrosine (DIT) are the specific iodinated forms of tyrosine produced within the thyroid gland.

• T4 and T3 Synthesis: The final thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are formed by coupling MIT and DIT molecules together.

• Within Thyroglobulin: The entire iodination and coupling process occurs on tyrosine residues that are part of a large protein scaffold known as thyroglobulin, stored in the thyroid follicles.

• Peripheral Conversion to T3: The majority of the highly active T3 hormone is formed from the conversion of T4 in peripheral tissues, not directly in the thyroid.

The Fundamental Role of Tyrosine

While there are 20 standard proteinogenic amino acids, only derivatives of one, tyrosine, are known to incorporate iodine directly during the normal biological process of thyroid hormone production. This crucial biochemical modification occurs exclusively within the thyroid gland, serving as the foundation for the body's metabolic regulation. The process involves the iodination of tyrosine residues that are part of a much larger protein called thyroglobulin.

The Multi-step Process of Iodination

The incorporation of iodine into tyrosine is a carefully regulated, multi-step process. Within the follicular cells of the thyroid gland, iodide from the bloodstream is actively transported and then undergoes a series of chemical transformations catalyzed by the enzyme thyroid peroxidase (TPO).

1. Iodide Uptake: Iodide (I-) is actively transported from the bloodstream into the thyroid follicular cells via the sodium-iodide symporter (NIS).
2. Oxidation: The TPO enzyme, located on the apical membrane, oxidizes the non-reactive iodide into a highly reactive iodine species.
3. Organification (Iodination): The active iodine then binds to specific tyrosine residues on the thyroglobulin protein, forming the first key iodine-containing amino acids: monoiodotyrosine (MIT) and diiodotyrosine (DIT).
4. Coupling Reaction: TPO facilitates the combination of these iodotyrosine residues to form the thyroid hormones. The coupling of two DIT molecules creates thyroxine (T4), while the combination of one MIT and one DIT forms triiodothyronine (T3).

The Final Hormones: Thyroxine (T4) and Triiodothyronine (T3)

After the iodination and coupling processes are complete, the newly formed T3 and T4 remain attached to the thyroglobulin molecule and are stored in the thyroid follicles. When the body signals for their release, thyroglobulin is endocytosed by the follicular cells and broken down by lysosomes, which liberates the free T3 and T4 hormones. These hormones are then secreted into the bloodstream, where they travel to target cells to regulate metabolism, growth, and development.

Beyond Tyrosine: The Role of Deiodinases

While T4 is the primary hormone secreted by the thyroid, the more potent and biologically active hormone is T3. The conversion of T4 to T3 occurs primarily in peripheral tissues like the liver and kidneys, a process facilitated by a family of enzymes called deiodinases. These enzymes contain a different, non-iodine-containing amino acid called selenocysteine, and their function is critical for proper thyroid hormone action.

Comparison of Iodinated Tyrosine Derivatives

This table highlights the differences between the key iodine-containing molecules derived from tyrosine.

Molecule Name	Chemical Origin	Number of Iodine Atoms	Role in Thyroid Synthesis
Tyrosine	A standard, non-iodinated amino acid.	0	The precursor to all iodinated thyroid compounds.
Monoiodotyrosine (MIT)	Tyrosine with a single iodine atom attached to its phenolic ring.	1	An intermediate in hormone synthesis; combines with DIT to form T3.
Diiodotyrosine (DIT)	Tyrosine with two iodine atoms attached to its phenolic ring.	2	An intermediate in hormone synthesis; combines with MIT to form T3 or another DIT to form T4.
Triiodothyronine (T3)	Formed by coupling one MIT and one DIT within thyroglobulin.	3	The most biologically active thyroid hormone, primarily responsible for metabolic effects.
Thyroxine (T4)	Formed by coupling two DIT molecules within thyroglobulin.	4	The major hormone secreted by the thyroid; acts as a prohormone and is converted to T3.

Conclusion: Tyrosine's Unique Contribution

The answer to which amino acids contain iodine is that only tyrosine is directly iodinated to form key precursors for the thyroid hormones T3 and T4. This fundamental process, orchestrated within the thyroid gland, transforms a single, common amino acid into powerful regulators of the body's metabolism. Without this specific biochemical pathway, the production of essential thyroid hormones would be impossible, underscoring iodine's critical role in human health. The transformation of tyrosine into these iodinated compounds is a prime example of the body's intricate and efficient use of nutrients to maintain complex systems like the endocrine feedback loop. For more detailed information on this process, consider reviewing resources like the NCBI article on Thyroid Hormone Physiology, which provides extensive physiological context beyond this summary.

Frequently Asked Questions

What is the difference between MIT and DIT?

MIT, or monoiodotyrosine, is a tyrosine molecule with one iodine atom, while DIT, or diiodotyrosine, is a tyrosine molecule with two iodine atoms.

How are T3 and T4 hormones formed from MIT and DIT?

Within the thyroglobulin protein, a molecule of MIT and a molecule of DIT are coupled to form T3. Two molecules of DIT are coupled to form T4.

Does the body create iodinated amino acids itself?

No, the body cannot create iodine. It must be obtained through dietary sources and then incorporated into the tyrosine amino acid within the thyroid gland during hormone synthesis.

What is the role of thyroglobulin in this process?

Thyroglobulin acts as a large protein scaffold where the tyrosine residues are iodinated and coupled to form T3 and T4. It also serves as a storage protein for these hormones until they are needed.

Where does the iodination of tyrosine take place?

The iodination of tyrosine residues occurs within the thyroid gland, in the colloid stored within the thyroid follicles.

Is T4 or T3 more active in the body?

T3 is the more metabolically active thyroid hormone. T4, while more abundant, is often considered a prohormone that is converted to T3 in peripheral tissues.

What is the purpose of the deiodinase enzymes?

Deiodinases are enzymes containing selenocysteine that convert T4 into the more active T3 hormone in various tissues throughout the body, regulating the local concentration of active thyroid hormone.