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Pathway Description
Thyroid Hormone Synthesis
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-09-12
Thyroid hormone synthesis is a process that occurs in the thyroid gland in humans that results in the production of thyroid hormones which regulate many different processes in the body, such as metabolism, temperature regulation and growth/development. Thyroid hormone synthesis begins in the nucleus of a thyroid follicular cell, as thyroglobulin synthesis occurs here and is transported to the endoplasmic reticulum. From there, thyroglobulin transported through endocytosis into the intracellular space, and then transported through exocytosis to the follicle colloid. There, thyroglobulin is joined by iodide that has been transported from the blood, through the thyroid follicular cell and arrived in the the follicle colloid using pendrin, and hydrogen peroxide to be catalyzed by thyroid peroxidase, creating thyroglobulin + iodotyrosine. Then, iodide, hydrogen peroxide and thyroidperoxidase create thyroglobulin + 3,5-diiodo-L-tyrosine. Thyroglobulin+3,5-diiodo-L-tyrosine then joins with hydrogen peroxide and thyroid peroxidase to create thyroglobulin + 2-aminoacrylic acid and thyroglobulin+liothyronine. Thyroglobulin + liothyronine then goes through two processes, the first being its transportation into the cell and undergoing of proteolysis, which is followed by liothyronine being transported into the bloodstream. The second process is thyroglobulin + liothyronine being catalyzed by thyroid peroxidase and resulting in the production of thyroglobulin + thyroxine. Thyroglobulin + thyroxine is then transported back into the cell, undergoes proteolysis, and thyroxine alone is transported back out of the cell and into the bloodstream.
References
Thyroid Hormone Synthesis References
Graves PN, Davies TF: A second thyroglobulin messenger RNA species (rTg-2) in rat thyrocytes. Mol Endocrinol. 1990 Jan;4(1):155-61. doi: 10.1210/mend-4-1-155.
Pubmed: 2325666
Hishinuma A, Furudate S, Oh-Ishi M, Nagakubo N, Namatame T, Ieiri T: A novel missense mutation (G2320R) in thyroglobulin causes hypothyroidism in rdw rats. Endocrinology. 2000 Nov;141(11):4050-5. doi: 10.1210/endo.141.11.7794.
Pubmed: 11089535
Musti AM, Avvedimento EV, Polistina C, Ursini VM, Obici S, Nitsch L, Cocozza S, Di Lauro R: The complete structure of the rat thyroglobulin gene. Proc Natl Acad Sci U S A. 1986 Jan;83(2):323-7. doi: 10.1073/pnas.83.2.323.
Pubmed: 3455768
Isozaki O, Kohn LD, Kozak CA, Kimura S: Thyroid peroxidase: rat cDNA sequence, chromosomal localization in mouse, and regulation of gene expression by comparison to thyroglobulin in rat FRTL-5 cells. Mol Endocrinol. 1989 Nov;3(11):1681-92. doi: 10.1210/mend-3-11-1681.
Pubmed: 2691880
Derwahl M, Seto P, Rapoport B: Complete nucleotide sequence of the cDNA for thyroid peroxidase in FRTL5 rat thyroid cells. Nucleic Acids Res. 1989 Oct 25;17(20):8380. doi: 10.1093/nar/17.20.8380.
Pubmed: 2813071
Banfi B, Malgrange B, Knisz J, Steger K, Dubois-Dauphin M, Krause KH: NOX3, a superoxide-generating NADPH oxidase of the inner ear. J Biol Chem. 2004 Oct 29;279(44):46065-72. doi: 10.1074/jbc.M403046200. Epub 2004 Aug 23.
Pubmed: 15326186
Fukui T, Lassegue B, Kai H, Alexander RW, Griendling KK: Cytochrome b-558 alpha-subunit cloning and expression in rat aortic smooth muscle cells. Biochim Biophys Acta. 1995 Oct 10;1231(3):215-9. doi: 10.1016/0005-2728(95)00098-4.
Pubmed: 7578211
Bayraktutan U, Blayney L, Shah AM: Molecular characterization and localization of the NAD(P)H oxidase components gp91-phox and p22-phox in endothelial cells. Arterioscler Thromb Vasc Biol. 2000 Aug;20(8):1903-11.
Pubmed: 10938010
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.
Pubmed: 22673903
Morand S, Dos Santos OF, Ohayon R, Kaniewski J, Noel-Hudson MS, Virion A, Dupuy C: Identification of a truncated dual oxidase 2 (DUOX2) messenger ribonucleic acid (mRNA) in two rat thyroid cell lines. Insulin and forskolin regulation of DUOX2 mRNA levels in FRTL-5 cells and porcine thyrocytes. Endocrinology. 2003 Feb;144(2):567-74. doi: 10.1210/en.2002-220824.
Pubmed: 12538618
De Deken X, Wang D, Many MC, Costagliola S, Libert F, Vassart G, Dumont JE, Miot F: Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. J Biol Chem. 2000 Jul 28;275(30):23227-33. doi: 10.1074/jbc.M000916200.
Pubmed: 10806195
Dupuy C, Pomerance M, Ohayon R, Noel-Hudson MS, Deme D, Chaaraoui M, Francon J, Virion A: Thyroid oxidase (THOX2) gene expression in the rat thyroid cell line FRTL-5. Biochem Biophys Res Commun. 2000 Oct 22;277(2):287-92. doi: 10.1006/bbrc.2000.3671.
Pubmed: 11032719
Geiszt M, Witta J, Baffi J, Lekstrom K, Leto TL: Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. FASEB J. 2003 Aug;17(11):1502-4. doi: 10.1096/fj.02-1104fje. Epub 2003 Jun 3.
Pubmed: 12824283
Hilenski LL, Clempus RE, Quinn MT, Lambeth JD, Griendling KK: Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2004 Apr;24(4):677-83. doi: 10.1161/01.ATV.0000112024.13727.2c. Epub 2003 Dec 11.
Pubmed: 14670934
Gorin Y, Block K, Hernandez J, Bhandari B, Wagner B, Barnes JL, Abboud HE: Nox4 NAD(P)H oxidase mediates hypertrophy and fibronectin expression in the diabetic kidney. J Biol Chem. 2005 Nov 25;280(47):39616-26. doi: 10.1074/jbc.M502412200. Epub 2005 Aug 31.
Pubmed: 16135519
Lassegue B, Sorescu D, Szocs K, Yin Q, Akers M, Zhang Y, Grant SL, Lambeth JD, Griendling KK: Novel gp91(phox) homologues in vascular smooth muscle cells : nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res. 2001 May 11;88(9):888-94. doi: 10.1161/hh0901.090299.
Pubmed: 11348997
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000716
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