Molecular Biology: Protein Structure and Function - Stepanov V.M. 2005

Post-translational protein modification
Iodination of tyrosine residues

This reaction is characteristic of thyroglobulin, a high-molecular-weight protein found in The Thyroid Gland that serves as the source of thyroxine, a hormone regulating metabolic processes in Tissues. The process begins with the selective iodination of a few Tyrosine residues within this protein by iodine, which is formed through the peroxidase-catalyzed oxidation of iodide ions:

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Iodine subsequently attacks the phenolic OH group of tyrosine via a radical mechanism and, by abstracting hydrogen to form HI, leaves an unpaired electron on the tyrosine oxygen. This electron is capable of delocalizing across the aromatic system of conjugated bonds and can be localized at the para-position, leading to the Cleavage of the C"—C_H2 bond via a so-called homolytic pathway. Next, the entire aromatic moiety, bearing an unpaired electron at the para-position, is intramolecularly transferred to the oxygen of a spatially close diiodotyrosine residue:

Studies on model Peptides have demonstrated that the yield of this non-enzymatic reaction depends on the relative spatial arrangement of the tyrosine residues. In thyroglobulin, this geometry appears to be exceptionally favorable for the process (requiring both aromatic rings to be coplanar). Within this protein, residues Tyr-5, 1291, 2555, and 2748 are preferentially iodinated and converted into thyroxine.

The release of thyroxine from thyroglobulin is mediated by a specific aspartic proteinase present in the thyroid gland.