Thyroxine (thyroid hormone) production (Homo sapiens)

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2, 3ATPcAMPH202PtdIns(4,5)P2 Iodination of tyrosineHypothalamusmono- anddi-iodotyrosinesSpontaneouscrosslinkingTriiodothyronine (T3)TSH127 IodideTRH131 IodideThyruglobulin (Tg)1ThyroidperoxidaseL-TyrosineThyroxine (T4)Anterior pituitaryFollicular lumen131 Iodide127 IodideThyroidDUOX systemBasolateral membrane ThyroidTSHRADCY1GαqPRKAA1 PRKAAK2 CREB1 CREB1 TG gene expressionRAP1A RAP1B MAPK21MAP2K2ERK1 ERK2 ELK1 PLC GαsIns(1,4,5)P3DAGPRKCA RAF1NF-KBCa2+131 Iodide127 IodideSLC5A5SLC26A6ANO1CLC5DUOX1DUOX2


Thyroxine hormone is produced in the thyroid gland from tyrosine and iodine. Thyrotropin-releasing hormone (TRH) is produced by the hypothalamus. It stimulates the production of thyroid-stimulating hormone (TSH) in the anterior pituitary gland, which affects the thyroid-stimulating hormone receptor (TSHR). Iodine is captured by a hydrogen peroxide trap procuced by thyroid peroxidase and added to the 3' and 5' postitions of tyrosine. This can either be free tyrosine or a tyrosine residue in thyroglobuline. After the multiple iodination steps this produces T3 and T4.

The production of the thyroid hormones thyroxine (T4),tri-iodothyronine (T3) and reverse T3 (rT3) is dependent on the organification of iodine into thyroglobulin (Tg), the major protein product of the thyroid (2). This involves thyroid peroxidase catalyzed iodination of tyrosine residues in Tg to form mono- and di-iodotyrosines and their subsequent crosslinking to form the iodothyronines T3 and T4.

Iodine 131 is an important radioactive fallout product. It was released in the atmosphere after nuclear tests and after nuclear incidents like at Tchernobyl and Fukushima. Since the iodine is concentrated in the thyroid glant as a substrate for the process described here non-radioactive iodine 127 is given as competitor to people exposed.

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  1. Van Herle, A.J ., G. Vassart, J.E . Dumont; ''Control of thyroglobulin synthesis and secretion''; N. Engl. J. Med. 301:239, 1979 PubMed Europe PMC Scholia
  2. Citterio CE, Targovnik HM, Arvan P; ''The role of thyroglobulin in thyroid hormonogenesis.''; Nat Rev Endocrinol, 2019 PubMed Europe PMC Scholia
  3. Ron E, Lubin JH, Shore RE, Mabuchi K, Modan B, Pottern LM, Schneider AB, Tucker MA, Boice JD Jr; ''Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies.''; Radiat Res, 1995 PubMed Europe PMC Scholia


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122822view16:35, 21 May 2022EgonwReplaced a secondary with a primary ChEBI identifier.
122778view13:21, 15 May 2022CMalyarFixed connection of the arrows
122777view12:11, 15 May 2022CMalyarChanged the interaction type between iodide and TPO
122743view19:43, 7 May 2022CMalyarModified visual structure, added new identifiers and references.
122704view09:43, 4 May 2022EgonwFixed metabolite identifiers (removed bad spaces)
122692view09:31, 3 May 2022CMalyar
122691view20:29, 2 May 2022CMalyar
122676view12:35, 1 May 2022CMalyar
117185view10:20, 18 May 2021EweitzModified title
106141view12:03, 16 August 2019MaintBotHMDB identifier normalization
96314view09:04, 8 March 2018Mkutmonremoved outdated pathway attributes
96012view14:53, 15 February 2018EgonwI need to dive into the exact mechanism... making it an plain arrow for now.
85189view15:40, 23 April 2016EgonwReplaced a mim-conversion with Arrow.
85188view15:38, 23 April 2016EgonwRemoved a "Label" label.
70955view21:25, 17 September 2013MaintBotadded xref for TG
70671view15:56, 24 August 2013EgonwAdded Pubchem-compound CIDs for the two 137I ions.
70030view01:57, 12 July 2013AlexanderPicoModified title
68909view17:30, 8 July 2013MaintBotUpdated to 2013 gpml schema
54373view15:18, 28 November 2012Mkutmonadded some labels and ioniation error
54372view15:10, 28 November 2012EveloModified description
54371view15:07, 28 November 2012EveloModified description
54364view14:51, 28 November 2012Mkutmonupdated MIM interactions
44968view13:21, 6 October 2011Mkutmonconnected lines
44471view20:38, 14 September 2011MaintBotAdded category
42772view17:05, 29 April 2011LribeiroPeriodical save, work in progress
42771view16:40, 29 April 2011LribeiroModified description
42770view15:39, 29 April 2011LribeiroModified description
42756view18:43, 28 April 2011LribeiroPeriodical save, work in progress
42755view18:32, 28 April 2011LribeiroPeriodical save, work in progress
42754view18:22, 28 April 2011LribeiroPeriodical save, work in progress
42742view19:56, 26 April 2011LribeiroPeriodical save, work in progress
42741view19:46, 26 April 2011LribeiroPeriodical save, work in progress
42740view19:36, 26 April 2011LribeiroPeriodical save, work in progress
42413view09:03, 23 March 2011EveloConnected some hormone interaction
42299view20:50, 14 March 2011EveloPeriodical save, work in progress
42298view20:04, 14 March 2011EveloAdded iodide symporter
42297view19:54, 14 March 2011EveloPeriodical save, work in progress
42296view19:24, 14 March 2011EveloOntology Term : 'thyroid hormone signaling pathway' added !
42295view19:22, 14 March 2011EveloOntology Term : 'thyroid gland disease' added !
42287view13:15, 14 March 2011EveloAdded organs
42286view12:43, 14 March 2011MkutmonCorrection of the name
42281view22:04, 13 March 2011EveloModified description
42280view22:00, 13 March 2011EveloSpecify description
42279view21:54, 13 March 2011EveloAdded TPO
42278view21:44, 13 March 2011EveloAdded Thyroglobulin
42277view21:26, 13 March 2011EveloModified description
42276view21:17, 13 March 2011EveloModified description
42275view21:11, 13 March 2011EveloSpecify description
42274view21:01, 13 March 2011EveloPeriodical save, work in progress
42273view20:49, 13 March 2011EveloAdde tyrosine

External references


View all...
NameTypeDatabase referenceComment
127 IodideMetaboliteHMDB0012238 (HMDB)
131 IodideMetabolite167195 (PubChem-compound)
ADCY1GeneProductENSG00000243989 (Ensembl)
ANO1GeneProductENSG00000131620 (Ensembl)
ATPMetaboliteHMDB0001532 (HMDB)
CLC5GeneProductENSG00000171365 (Ensembl)
CREB1 GeneProductP16220 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
DAGMetaboliteCHEBI:18035 (ChEBI)
DUOX1GeneProductENSG00000137857 (Ensembl)
DUOX2GeneProductENSG00000140279 (Ensembl)
ELK1 GeneProduct2002 (Entrez Gene)
ERK1 GeneProduct5595 (Entrez Gene)
ERK2 GeneProduct5594 (Entrez Gene)
H202MetaboliteCHEBI:16240 (ChEBI)
Ins(1,4,5)P3MetaboliteCHEBI:138527 (ChEBI)
L-TyrosineMetaboliteHMDB0000158 (HMDB)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAPK21GeneProductENSG00000169032 (Ensembl)
NF-KBGeneProductP19838 (Uniprot-TrEMBL)
PLC GeneProductPP51178 (Uniprot-TrEMBL)
PRKAA1 GeneProductENSG00000132356 (Ensembl)
PRKAAK2 GeneProductENSG00000162409 (Ensembl)
PRKCA GeneProductENSG00000154229 (Ensembl)
PtdIns(4,5)P2 MetaboliteCHEBI:83416 (ChEBI)
RAF1GeneProductP04049 (Uniprot-TrEMBL)
RAP1A GeneProductP62834 (Uniprot-TrEMBL)
RAP1B GeneProductP61224 (Uniprot-TrEMBL)
SLC26A6GeneProductENSG00000225697 (Ensembl)
SLC5A5GeneProduct6528 (Entrez Gene)
TRHGeneProduct7200 (Entrez Gene)
TSHGeneProduct1081 (Entrez Gene)
TSHRGeneProduct7253 (Entrez Gene)
Thyroidperoxidase GeneProduct7173 (Entrez Gene)
Thyroxine (T4)MetaboliteHMDB0000248 (HMDB)
Thyruglobulin (Tg)GeneProduct7038 (Entrez Gene)
Triiodothyronine (T3)Metabolite5707 (Chemspider)
cAMPMetaboliteHMDB0000058 (HMDB)

Annotated Interactions

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