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Iodine Research

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Iodine and the Body

THYROID HORMONE SYNTHESIS

Once the iodide is in the cell, it must be transformed into thyroid hormones and stored
until it is needed.

To create the hormones, the iodide must be attached to the tyrosine molecule.  In other
words, the tyrosine must be "iodinated".  The iodination requires four separate
components in close proximity:  iodide, hydrogen peroxide (H2O2), thyroid peroxidase
(TPO, an enzyme) and thyroglobulin (Tg)

First, the iodide must be oxidized (have electrons removed) to change the iodide to a
form of iodine (e.g., I+ or OI-) capable of attaching to the tyrosine.   Hydrogen Peroxide
(H2O2) is important for this chemical transformation.  

Second, the transformed iodide must react with the tyrosine that is an integral part of
the giant thyroglobulin molecule.  Binding with one of the transformed iodide atom
yields monoiodotyrosine (T1); binding with two atoms produces diiodotyrosine(T2).  
Thyroid peroxidase (TPO) is the enzyme that catalyzes this reaction.

Third, the molecules must be combined to create the hormones.  Two T2 molecules join
to form T4, or one T1 and one T2 join to from T3.  The thyroid peroxidase (TPO) and
thyroglobulin (Tg) are both important in this process.

Fourth, the thyroid hormones are stored with the thyroglobulin until they are needed.  

Finally, the hormones are separated from the thyroglobulin and secreted into the blood
stream, where 99+% combine with transport proteins.  (See Diagram.)

THYROID HORMONE SYNTHESIS





























FIG. 1. Schematic representation of  thyroid hormones synthesis in the thyroid
follicular cell.

Thyroid follicles are comprised of a layer of epithelial (covering or surface) cells
surrounding the colloid (the gelatinous center of the thyroid cell, consisting mainly of
thyroglobulin).

The basolateral (near the blood vessel) surface of the cell  is shown on the left side of
the figure and the apical surface (next to the colloid) on the right.

Symbols:
Circle = Active accumulation of I-, mediated by the NIS;
Triangle =  Na+/K+ ATPase; square, TSH receptor;
Diamond = adenylate cyclase; ellipse, G protein;
Cylinder =  I- efflux toward the colloid;
Arrows pointing from the apical to the basolateral side = endocytosis of iodinated Tg,
followed by phagolysosomal hydrolysis of endocytosed iodinated Tg and secretion of
both thyroid hormones.

Abbreviations:
AIT =  Apical I- Transporter
Cl- = Chloride
I- = Iodide
K = Potassium
Na+ = Sodium
NIS = Sodium-Iodide Transporter
Pendrin = Iodide transporter on apical membrane
Tg = Thyroglobulin
TPO = Thyroid Peroxidase, TPO-catalyzed organification of I-
TSH-R = Thyroid Stimulating Hormone - Receptor

Adapted from:  The Sodium/Iodide Symporter (NIS): Characterization, Regulation, and
Medical Significance.  By ORSOLYA DOHA´ N, ANTONIO DE LA VIEJA, VIKTORIYA
PARODER, CLAUDIA RIEDEL, MONA ARTANI, MIA REED, CHRISTOPHER S. GINTER,
AND NANCY CARRASCO (2003)
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