Pathway of Iodine Through the Thyroid
Iodine / Iodide ingested - Some can convert Iodine to Iodide but many have trouble doing this...
Iodide travels to the small intestine and is absorbed into the blood stream.
Blood passes through the Thyroid where it traps the iodide into the follicles via pendrin and NaI.
If there is a deficiency of iodine the thyroid enlarges in an attempt to trap more iodine.
TSH stimulates a basolateral plasma membrane protein (NIS) for accumulation of I- acting at the level of NIS gene transcription
NIS gene expression in the thyroid cells are regulated by thyrotropin (TSH) via the cAMP dependent pathway.
mRNA expression is enhanced by TSH & cAMP and decreased by iodide.
I- is carried across the basolateral membrane via ATP into the follicular cells
The concentration is dependant on the electro chemical gradient of Na+.
This gradient is maintained by the Na+/K+ ATPase
Once inside the cell iodide is oxidzed into iodine. This means that one electron has been dropped. This process occurs with the reaction of hydrogen peroxide (H2O2) with thyroperoxidase (TPO). Abnormalities here can cause the body to create Anti-TPO antibodies. This leads to Hashimoto's disease
Transported iodine is organified as Tg on the rough endoplasmic reticulum by the action of thyroperoxidases (TPO), which is an enzyme that when expressed liberates iodine for the covalent bonding to tyrosine (an amino acid) residue on thyroglobulin forming monoiodotyrosine (MIT) and diiodotyrosine (DIT) or Iodotyrosines.
DIT- Tyrosine with two iodine atoms added.
MIT- Tyrosine with one iodine atom added
The thyroglobulin iodination occurs in the colloid.
Coupling of the iodotyrosyl residues forms T4 (2-DIT) & T3 (1-DIT & 1-MIT)
Proteases digest the iodinated thyroglobulin releasing T4 & T3 hormones
Each thyroglobulin residue contains two MIT, four DIT, two T4 and one third T3, meaning only one in three thyroglobulins contain a T3.
T4 is converted in the tissue by deiodinases
Deiodinases are unusual in that the enzyme contains selenium, in the form of a rare amino acid selenocysteine
Deficiency in deiodinases can mimic iodine deficiency.