A Gland Cell With Two Unlike Membrane Faces

The Blood Face and the Colloid Face of the Follicle Cell

The thyroid consists of many small sacs known as follicles. Their wall is a single layer of cells, and every one of these cells has a clear orientation: one face borders fine blood vessels, the other the colloid inside the follicle. The two membranes carry different proteins, and it is precisely this split that allows the steps to run in sequence.

Facing the Capillary: Uptake

The sodium-iodide carrier does its work on the basolateral face. It relies on the sodium-potassium pump in the same membrane constantly moving sodium out of the cell. Only then does the gradient persist along which sodium and iodide flow in together.

Facing the Colloid: Release and Incorporation

The apical face is covered in small projections and holds the proteins for the later steps. This is where iodide leaves the cell, where hydrogen peroxide is made, and where thyroid peroxidase sits with its active site turned toward the colloid.

Molecules involved and where they sit in the follicle cell (simplified)

Molecule	Where in the cell	Task in the sequence
Sodium-potassium pump	Capillary-facing membrane	keeps the sodium gradient in place
NIS (SLC5A5)	Capillary-facing membrane	takes in 2 Na+ and 1 I− together
Pendrin (SLC26A4)	Colloid-facing membrane	releases iodide in exchange for other anions
Anoctamin-1	Colloid-facing membrane	extra channel through which iodide exits
DUOX2 with DUOXA2	Colloid-facing membrane	generates hydrogen peroxide
Thyroid peroxidase	Colloid-facing membrane	oxidizes iodide, iodinates tyrosines, couples them
MCT8	Capillary-facing membrane	moves released hormones out of the cell

Where the Iodide in Plasma Originates

The body cannot make iodine on its own. It reaches the gut with food and drink, is absorbed there almost entirely as iodide, and travels to the thyroid through the blood. How much any one meal adds is hard to put in a single figure; the table only names what that amount hinges on.

Origin of the iodide	What the amount hinges on
Saltwater fish	Species and where it was caught
Milk and dairy products	Iodine content of the animal feed
Iodized table salt	National rules on fortification

Iodide Turns Into Reactive Iodine

As an ion, iodide is chemically sluggish; in that form it will not bind to a tyrosine ring. Only when electrons are taken from it does an intermediate form that reacts with the ring. The cell cannot leave this step to chance, since the oxidant it needs is reactive in its own right.

Hydrogen Peroxide Made Right at the Membrane

Dual oxidase 2 passes electrons from NADPH to oxygen and in doing so releases hydrogen peroxide. For the enzyme to reach the correct membrane in the first place, it needs a maturation protein, DUOXA2. The hydrogen peroxide therefore appears on the outer surface of the apical membrane, right where thyroid peroxidase uses it, rather than somewhere in the cell interior.

Monoiodotyrosine and Diiodotyrosine

Thyroid peroxidase is a heme enzyme from the same family as the myeloperoxidase found in white blood cells. With the hydrogen peroxide it oxidizes iodide and places the iodine at position 3 of a tyrosine ring. A second iodine atom can follow at position 5. In this way monoiodotyrosine and diiodotyrosine residues form on thyroglobulin. Of the protein’s many tyrosines only some are iodinated, and only a handful of those lie where they can later be coupled into hormones.

The Coupling Reaction and How Much of Each Hormone Is Iodine

Next, thyroid peroxidase joins two iodinated tyrosine residues that sit close together in the folded chain. The aromatic ring of one residue is shifted onto the other by way of an oxygen bridge. At the donor position a residue is left behind that carries no hormone. The hormone itself remains firmly in place within thyroglobulin.

Two diiodotyrosines yield thyroxine (T4); one monoiodotyrosine together with one diiodotyrosine yields triiodothyronine (T3). Running the numbers on the molar masses reveals how much of these molecules the halogen makes up.

Iodine in the intermediates and the hormones (molar masses rounded)

Compound	Number of iodine atoms	Molar mass in g/mol	Iodine as share of mass
Monoiodotyrosine (MIT)	1	307	about 41%
Diiodotyrosine (DIT)	2	433	about 59%
Triiodothyronine (T3)	3	651	about 58%
Thyroxine (T4)	4	777	about 65%

So nearly two thirds of a thyroxine molecule’s mass comes from its four iodine atoms, even though they account for only four of the molecule’s 35 atoms.

Stockpile, Retrieve, Reuse

Iodinated thyroglobulin stays in the colloid for the time being. The follicle thus acts as a reserve from which the cell can release hormone without building every molecule from the ground up.

Endocytosis and Lysosomes

To release hormone, the cell wraps small portions of colloid in its apical membrane and draws them inside as vesicles. These merge with lysosomes, whose proteases, several cathepsins among them, cut thyroglobulin into fragments and single amino acids. T4 and T3 are set free along the way and exit the cell on the capillary side, one route being the membrane protein MCT8.

Recycling the Tyrosines That Were Never Coupled

Breakdown also leaves behind many MIT and DIT residues that never ended up in a hormone. The cell does not throw away the iodine bound to them. The enzyme iodotyrosine dehalogenase 1 (IYD, also called DEHAL1), a flavoprotein, detaches the iodine from these residues. The freed iodide is then ready to be used for iodination once more.

Gaps That Surface on a Careful Read