Biosynthesis of T4 and T3 Hormones

Study Notes

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.

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.

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 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.

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.