Editing Thyroxine

{{short description|Thyroid hormone}}
{{About|thyroxine as a hormone|its use as a medication|levothyroxine|the family of thyroid hormones|thyroid hormones}}
{{cs1 config|name-list-style=vanc|display-authors=6|display-editors=6}}

{{Chembox
| ImageFile      = Thyroxine2.svg
| ImageFile1     = Thyroxine-3D-Sylocin.png
| ImageClass     = skin-invert-image
| ImageSize      = 
| ImageAlt       = 
| IUPACName      = 
| OtherNames     = O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine, (-)-thyroxine, 3,3′,5,5′-tetraiodo-L-thyronine
| Section1       = {{Chembox Identifiers
| CASNo = 51-48-9
| CASNo_Comment = l enantiomer
| CASNo1 = 300-30-1
| CASNo1_Comment = DL
| ChEBI = 30660
| ChEMBL = 42115
| ChemSpiderID = 830
| EC_number = 206-088-9
| PubChem = 853
| UNII = QR0BV3BRIA
| StdInChI=1S/C15H11I4NO4/c16-8-4-7(5-9(17)13(8)21)24-14-10(18)1-6(2-11(14)19)3-12(20)15(22)23/h1-2,4-5,12,21H,3,20H2,(H,22,23)
| StdInChIKey = XUIIKFGFIJCVMT-UHFFFAOYSA-N
| SMILES = C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)CC(C(=O)O)N
 }}
| Section2       = {{Chembox Properties
| C=15|H=11|I=4|N=1|O=4 
| MolarMass =
| Appearance = white solid
| Density = 
| MeltingPtC = 235–236 
| MeltingPt_notes = 
| BoilingPt = 
| BoilingPt_notes =
| Solubility = }}
| Section3       = {{Chembox Hazards
| MainHazards = 
| FlashPt = 
| AutoignitionPt = }}
}}

'''Thyroxine''', also known as '''T<sub>4</sub>''', is a [[hormone]] produced by the [[thyroid gland]]. It is the primary form of [[thyroid hormone]] found in the blood and acts as a [[prohormone]] of the more active thyroid hormone, [[triiodothyronine]] (T<sub>3</sub>).<ref name="Li_2020">{{cite journal | vauthors = Li J, Bai L, Wei F, Wei M, Xiao Y, Yan W, Wei J | title = Effect of Addition of Thyroxine in the Treatment of Graves' Disease: A Systematic Review | journal = Frontiers in Endocrinology | volume = 11 | pages = 560157 | date = 2020 | pmid = 33569041 | pmc = 7868565 | doi = 10.3389/fendo.2020.560157 | doi-access = free }}</ref> Thyroxine and its active metabolites are essential for regulating [[metabolic rate]], supporting heart and [[muscle contraction|muscle function]], promoting [[brain development]], and maintaining [[bone health]].<ref name="Kim_2013">{{cite journal | vauthors = Kim HY, Mohan S | title = Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development | journal = Bone Research | volume = 1 | issue = 2 | pages = 146–161 | date = June 2013 | pmid = 26273499 | pmc = 4472099 | doi = 10.4248/BR201302004 }}</ref><ref name="Mullur_2014">{{cite journal | vauthors = Mullur R, Liu YY, Brent GA | title = Thyroid hormone regulation of metabolism | journal = Physiological Reviews | volume = 94 | issue = 2 | pages = 355–82 | date = April 2014 | pmid = 24692351 | pmc = 4044302 | doi = 10.1152/physrev.00030.2013 }}</ref>

== Regulation ==

Thyroxine has a [[half-life]] of approximately one week and hence maintains relatively stable blood levels. Its production and release are controlled through a complex feedback loop involving the [[hypothalamus]], [[pituitary gland]], and thyroid gland. This regulatory system ensures that optimal hormone levels are maintained.<ref name = "Rousset_2015">{{cite book | vauthors = Rousset B, Dupuy C, Miot F, Dumont J | chapter = Chapter 2 Thyroid Hormone Synthesis And Secretion | date = September 2015 | veditors = Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP | title = Endotext [Internet] | location = South Dartmouth (MA) | publisher = MDText.com, Inc. | pmid = 25905405 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK285550/ }}</ref>

== 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" />

== References ==
{{Reflist}}

[[Category:Iodinated tyrosine derivatives]]
[[Category:Hormones of the thyroid gland]]
[[Category:Hormones of the hypothalamus-pituitary-thyroid axis]]
[[Category:Human hormones]]
[[Category:Thyroid]]
[[Category:Diphenyl ethers]]