In blood plasma, iodine is present as the negatively charged iodide ion, and only in trace amounts. Thyroid cells nonetheless gather this very ion to many times its plasma level. Mere seepage could never build up a difference like that; the cell has to put work into it.
Enstatitys follows one iodide ion through a follicle cell: in across the membrane that borders the capillary, out across the opposite membrane into the hollow of the follicle, then onto a large storage protein and finally into a finished hormone molecule. Each of these steps has a known, named protein attached to it.
Standard textbook figures place the larger part of an adult’s total body iodine in this single organ. That makes the thyroid the natural place to look when asking what the organism draws on this halogen for at all.
Enstatitys · Thyroid Biochemistry
The element itself, plus three proteins that mark out its path through the cell. The authorized EU wording is printed alongside the element.
A halogen with atomic number 53. In the body it turns up almost only in two states: as a free iodide ion in the body fluids, and covalently bound to the aromatic ring of the amino acid tyrosine.
EU-authorized wording · Regulation (EU) No 432/2012
It sits in the membrane that faces the capillary and takes in two sodium ions together with one iodide ion. The driving force is the sodium gradient, which the sodium-potassium pump keeps up by spending ATP.
An enzyme with a heme group, anchored in the membrane that faces the inside of the follicle. It pulls electrons away from iodide, using up hydrogen peroxide as it does so, and attaches the reactive iodine to selected tyrosines.
A glycoprotein of about 660 kilodaltons that fills the follicle. It serves as scaffold and warehouse in one: the hormones take shape within its chain and stay bound there until the cell takes the protein back in and dismantles it.
The brief portraits above introduce the participants. The sections below show the order in which they cooperate and the point where iodide is chemically altered.
NIS belongs to the SLC5 protein family. On every cycle it carries two positively charged sodium ions and one negatively charged iodide ion, so that one net positive charge enters the cell. Because there is far more sodium outside the cell than inside, the sodium, so to speak, “drags” the iodide in with it. The gene for this carrier protein was cloned in 1996 by the research group led by Nancy Carrasco.
In the lab, NIS can be slowed down by anions of similar size, such as perchlorate or thiocyanate, which compete with iodide for the binding site. These observations went a long way toward working out how the uptake mechanism operates.
On the opposite side, iodide exits the cell again and passes into the colloid, the thick filling of the follicle. Proteins described for this step include the anion exchanger pendrin and the channel anoctamin-1. Right at this membrane the enzyme dual oxidase 2 (DUOX2) produces hydrogen peroxide, exactly at the spot where it is needed.
Thyroid peroxidase uses this hydrogen peroxide to oxidize iodide. The activated iodine binds to the ring of particular tyrosine residues in thyroglobulin. A ring carrying one iodine atom is called monoiodotyrosine (MIT); a ring carrying two is diiodotyrosine (DIT). Specialists refer to this incorporation into a protein as organification. It is the biochemical backdrop to the sentence the EU has authorized for iodine:
“Iodine contributes to the normal production of thyroid hormones and normal thyroid function” — EU-authorized wording · Regulation (EU) No 432/2012
While everything is still on thyroglobulin, thyroid peroxidase links two iodinated tyrosines to each other. Two DIT residues give thyroxine (T4), with four iodine atoms; one MIT residue plus one DIT residue give triiodothyronine (T3), with three. The finished hormones stay attached to the protein chain and are stored in the colloid.
NIS, pendrin, DUOX2 and thyroid peroxidase are not named in the legal text. They show where an iodide ion is put to use; the authorized claim, on the other hand, only describes the outcome in the normal case and names no extra beyond that normal case.
Every stop iodide makes in the follicle cell, each with a labeled sketch, plus a table of the proteins involved and references to the original research papers.
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Enstatitys explains biochemical processes in general terms. These texts do not stand in for a diagnosis, a therapy decision or a conversation with your physician; questions about your own thyroid belong in a specialist’s consulting room.
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