(NIS) located in the
basolateral membrane. Once inside the cell, iodide is transported to the follicular lumen, where it undergoes oxidation by the enzyme
thyroid peroxidase (TPO) in the presence of
hydrogen peroxide generated by the
NADPH oxidase
DUOX2. The oxidized iodine then iodinates tyrosyl residues of
thyroglobulin (Tg), a
glycoprotein synthesized by thyroid cells and stored in the follicular lumen. This process, known as
organification, results in the formation of
monoiodotyrosine (MIT) and
diiodotyrosine (DIT) residues within the Tg molecule. The final step in thyroxine synthesis involves the
free radical mediated coupling of two DIT residues, catalyzed by TPO, to form T4 while still attached to the Tg backbone. When thyroid hormone is needed, Tg is internalized by thyrocytes, and proteolytic enzymes in lysosomes cleave the T4 from Tg, allowing for its release into the bloodstream. This intricate biosynthetic pathway is tightly regulated by
thyroid-stimulating hormone (TSH) from the pituitary gland, which influences virtually every stage of thyroid hormone production. == References ==