Editing Thyroxine (section)

== Biosynthesis ==
[[File:Thyroxine biosynthesis.svg|class=skin-invert-image|thumb|left|Biosynthesis of thyroxine<ref name = "Rousset_2015" />]]
Thyroxine biosynthesis is a multi-step process that occurs in [[Thyroid follicular cell|follicular cell]] within the thyroid gland. The synthesis of thyroxine requires adequate [[iodine]] supply and appropriate hormonal control.<ref name="Sorrenti_2021">{{cite journal | vauthors = Sorrenti S, Baldini E, Pironi D, Lauro A, D'Orazi V, Tartaglia F, Tripodi D, Lori E, Gagliardi F, Praticò M, Illuminati G, D'Andrea V, Palumbo P, Ulisse S | title = Iodine: Its Role in Thyroid Hormone Biosynthesis and Beyond | journal = Nutrients | volume = 13 | issue = 12 | date = December 2021 | page = 4469 | pmid = 34960019 | pmc = 8709459 | doi = 10.3390/nu13124469 | doi-access = free }}</ref><ref name = "Shahid_2023">{{cite book | vauthors = Shahid MA, Ashraf MA, Sharma S | chapter = Physiology, Thyroid Hormone | date = June 2023 | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 29763182 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK500006/ }}</ref><ref name = "Rousset_2015" />

The process begins with the active uptake of iodide from the bloodstream by thyroid follicular cells through the [[Sodium/iodide cotransporter|sodium/iodide symporter]] (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]].<ref name = "Shahid_2023" /> The oxidized iodine then iodinates tyrosyl residues of [[thyroglobulin]] (Tg), a [[glycoprotein]] synthesized by thyroid cells and stored in the follicular lumen.<ref name="Sorrenti_2021" /> This process, known as [[organification]], results in the formation of [[monoiodotyrosine]] (MIT) and [[diiodotyrosine]] (DIT) residues within the Tg molecule.<ref name = "Shahid_2023" /><ref name = "Rousset_2015" />

The final step in thyroxine synthesis involves the [[free radical]] mediated coupling of two DIT residues, catalyzed by TPO, to form T<sub>4</sub> while still attached to the Tg backbone.<ref name="Sorrenti_2021" /><ref name = "Shahid_2023" /> When thyroid hormone is needed, Tg is internalized by thyrocytes, and proteolytic enzymes in lysosomes cleave the T<sub>4</sub> from Tg, allowing for its release into the bloodstream.<ref name = "Rousset_2015" /> 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.<ref name = "Rousset_2015" />