Biosynthesis of T4 and T3 Hormones

Biosynthesis of T4 and T3

• The process of biosynthesis of T4 and T3 occurs through four steps: concentration of iodide, oxidation of iodide, iodination of tyrosine, and coupling.
• The first step, concentration of iodide, is a rate-limiting step and is controlled by TSH.

Concentration of Iodide

• Iodide is present in small amounts in food, so the thyroid gland has a mechanism to acquire it.
• The thyroid gland concentrates iodide to a ratio of 25:1 compared to iodide in serum.

Oxidation of Iodide

• The thyroid gland is the only tissue that can oxidize iodide to iodine, which is essential for T4 and T3 synthesis.
• This step is catalyzed by the thyroperoxidase enzyme and occurs at the luminal surface of the follicular cell.

Iodination of Tyrosine

• Iodination of tyrosine leads to the formation of 3 monoiodotyrosine (MIT) and 3,5 diiodotyrosine (DIT).
• This process occurs in thyroglobulin and is catalyzed by the thyroperoxidase enzyme.
• Thyroglobulin is a large, iodinated, glycosylated protein with a molecular mass of 660 kDa, consisting of two large subunits.
• It contains 115 tyrosine residues on its surface, each of which is a potential site of iodination.

Coupling

• The coupling reaction leads to the formation of T4 if coupling occurs between two DIT molecules, and T3 if coupling occurs between MIT and DIT.
• This process occurs within the thyroglobulin molecule in the colloid and is catalyzed by a coupling enzyme thought to be thyroperoxidase.
• Thyroglobulin stored in the colloid contains a mixture of MIT, DIT, T3, and T4, with approximately 70% of tyrosine present in the form of MIT and DIT, and 30% in the form of T3 and T4, with a T4:T3 ratio of about 7:1.