Thyroxine

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Thyroxine
Thyroxine2.svg
Thyroxine-3D-Sylocin.png
Names
Other names
O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo-L-tyrosine, (-)-thyroxine, 3,3′,5,5′-tetraiodo-L-thyronine
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
EC Number
  • 206-088-9
PubChem CID
UNII
  • InChI=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)
    Key: XUIIKFGFIJCVMT-UHFFFAOYSA-N
  • C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)CC(C(=O)O)N
Properties
C15H11I4NO4
Molar mass 776.874 g·mol−1
Appearancewhite solid
Melting point 235-236
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Thyroxine, also known as T4, 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 (T3). [1] Thyroxine and its active metabolites are essential for regulating metabolic rate, supporting heart and muscle function, promoting brain development, and maintaining bone health. [2] [3]

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. [4]

Biosynthesis

Biosynthesis of thyroxine Thyroxine biosynthesis.svg
Biosynthesis of thyroxine

Thyroxine biosynthesis is a multi-step process that occurs in follicular cell within the thyroid gland. The synthesis of thyroxine requires adequate iodine supply and appropriate hormonal control. [5] [6] [4]

The process begins with the active uptake of iodide from the bloodstream by thyroid follicular cells through the 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. [6] The oxidized iodine then iodinates tyrosyl residues of thyroglobulin (Tg), a glycoprotein synthesized by thyroid cells and stored in the follicular lumen. [5] This process, known as organification, results in the formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT) residues within the Tg molecule. [6] [4]

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. [5] [6] 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. [4] 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. [4]

References

  1. ↑ Li J, Bai L, Wei F, Wei M, Xiao Y, Yan W, et al. (2020). "Effect of Addition of Thyroxine in the Treatment of Graves' Disease: A Systematic Review". Frontiers in Endocrinology. 11: 560157. doi: 10.3389/fendo.2020.560157 . PMC   7868565 . PMID   33569041.
  2. ↑ Kim HY, Mohan S (June 2013). "Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development". Bone Research. 1 (2): 146–161. doi:10.4248/BR201302004. PMC   4472099 . PMID   26273499.
  3. ↑ Mullur R, Liu YY, Brent GA (April 2014). "Thyroid hormone regulation of metabolism". Physiological Reviews. 94 (2): 355–82. doi:10.1152/physrev.00030.2013. PMC   4044302 . PMID   24692351.
  4. 1 2 3 4 5 6 Rousset B, Dupuy C, Miot F, Dumont J (September 2015). "Chapter 2 Thyroid Hormone Synthesis And Secretion". In Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al. (eds.). Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc. PMID   25905405.
  5. 1 2 3 Sorrenti S, Baldini E, Pironi D, Lauro A, D'Orazi V, Tartaglia F, et al. (December 2021). "Iodine: Its Role in Thyroid Hormone Biosynthesis and Beyond". Nutrients. 13 (12): 4469. doi: 10.3390/nu13124469 . PMC   8709459 . PMID   34960019.
  6. 1 2 3 4 Shahid MA, Ashraf MA, Sharma S (June 2023). "Physiology, Thyroid Hormone". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID   29763182.
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