KEGG   PATHWAY: mmu04918
Entry
mmu04918                    Pathway                                
Name
Thyroid hormone synthesis - Mus musculus (house mouse)
Description
Thyroid hormones triiodothyronine (T3) and thyroxine (T4) are essential for normal development, growth and metabolic homeostasis in all vertebrates, and synthesized in the thyroid gland. The functional unit of the thyroid gland is the follicle, delimited by a monolayer of thyrocytes. Polarized thyrocytes surround the follicular lumen; with their basal and apical surfaces facing the bloodstream and the lumen, respectively. To synthesize thyroid hormones, thyrocytes take up iodide at their basal side and concentrate it into the lumen. They also secrete in this lumen the specialized protein thyroglobulin (TG) which serves as a store for the hormones. In the follicular lumen oxidation of iodine, iodination of tyrosines (MIT, 3-monoiodotyrosine; DIT, 3,5-diiodotyrosine) and coupling of iodotyrosines takes place on tyrosine residues in TG, resulting in T3 and T4 synthesis. Iodinated TG is resorbed through the apical membrane and degraded to form T3/T4 in lysosomes; the T3/T4 is then secreted through the basal membrane.
Class
Organismal Systems; Endocrine system
Pathway map
mmu04918  Thyroid hormone synthesis
mmu04918

Other DBs
GO: 0006590
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
22094  Tshb; thyroid stimulating hormone, beta subunit [KO:K05251]
12640  Cga; glycoprotein hormones, alpha subunit [KO:K08522]
22095  Tshr; thyroid stimulating hormone receptor [KO:K04249]
14683  Gnas; GNAS complex locus [KO:K04632]
432530  Adcy1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
210044  Adcy2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
104111  Adcy3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
104110  Adcy4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
224129  Adcy5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
11512  Adcy6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
11513  Adcy7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
11514  Adcy8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
11515  Adcy9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
18747  Prkaca; protein kinase, cAMP dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
18749  Prkacb; protein kinase, cAMP dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
14682  Gnaq; guanine nucleotide binding protein, alpha q polypeptide [KO:K04634]
18795  Plcb1; phospholipase C, beta 1 [KO:K05858] [EC:3.1.4.11]
18797  Plcb3; phospholipase C, beta 3 [KO:K05858] [EC:3.1.4.11]
18798  Plcb4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
18796  Plcb2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
18750  Prkca; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
18751  Prkcb; protein kinase C, beta [KO:K19662] [EC:2.7.11.13]
18752  Prkcg; protein kinase C, gamma [KO:K19663] [EC:2.7.11.13]
22130  Ttf1; transcription termination factor, RNA polymerase I [KO:K15225]
74044  Ttf2; transcription termination factor, RNA polymerase II [KO:K15173] [EC:5.6.2.-]
18510  Pax8; paired box 8 [KO:K09293]
12912  Creb1; cAMP responsive element binding protein 1 [KO:K05870]
11909  Atf2; activating transcription factor 2 [KO:K04450]
11911  Atf4; activating transcription factor 4 [KO:K04374]
12913  Creb3; cAMP responsive element binding protein 3 [KO:K09048]
26427  Creb3l1; cAMP responsive element binding protein 3-like 1 [KO:K09048]
208647  Creb3l2; cAMP responsive element binding protein 3-like 2 [KO:K09048]
208677  Creb3l3; cAMP responsive element binding protein 3-like 3 [KO:K09048]
78284  Creb3l4; cAMP responsive element binding protein 3-like 4 [KO:K09048]
231991  Creb5; cAMP responsive element binding protein 5 [KO:K09047]
12915  Atf6b; activating transcription factor 6 beta [KO:K09049]
21819  Tg; thyroglobulin [KO:K10809]
14828  Hspa5; heat shock protein 5 [KO:K09490] [EC:3.6.4.10]
22027  Hsp90b1; heat shock protein 90, beta (Grp94), member 1 [KO:K09487]
12330  Canx; calnexin [KO:K08054]
12304  Pdia4; protein disulfide isomerase associated 4 [KO:K09582] [EC:5.3.4.1]
11889  Asgr1; asialoglycoprotein receptor 1 [KO:K10063]
11890  Asgr2; asialoglycoprotein receptor 2 [KO:K10064]
16438  Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958]
16439  Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959]
16440  Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960]
114479  Slc5a5; solute carrier family 5 (sodium iodide symporter), member 5 [KO:K14385]
23985  Slc26a4; solute carrier family 26, member 4 [KO:K14702]
22018  Tpo; thyroid peroxidase [KO:K00431] [EC:1.11.1.8]
11928  Atp1a1; ATPase, Na+/K+ transporting, alpha 1 polypeptide [KO:K01539] [EC:7.2.2.13]
98660  Atp1a2; ATPase, Na+/K+ transporting, alpha 2 polypeptide [KO:K01539] [EC:7.2.2.13]
232975  Atp1a3; ATPase, Na+/K+ transporting, alpha 3 polypeptide [KO:K01539] [EC:7.2.2.13]
27222  Atp1a4; ATPase, Na+/K+ transporting, alpha 4 polypeptide [KO:K01539] [EC:7.2.2.13]
67821  Atp1b4; ATPase Na+/K+ transporting, beta 4 polypeptide [KO:K01540]
11931  Atp1b1; ATPase, Na+/K+ transporting, beta 1 polypeptide [KO:K01540]
11932  Atp1b2; ATPase, Na+/K+ transporting, beta 2 polypeptide [KO:K01540]
11933  Atp1b3; ATPase, Na+/K+ transporting, beta 3 polypeptide [KO:K01540]
11936  Fxyd2; FXYD domain-containing ion transport regulator 2 [KO:K01538]
70337  Iyd; iodotyrosine deiodinase [KO:K17231] [EC:1.21.1.1]
66811  Duoxa2; dual oxidase maturation factor 2 [KO:K17232]
99439  Duox1; dual oxidase 1 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
214593  Duox2; dual oxidase 2 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
14775  Gpx1; glutathione peroxidase 1 [KO:K00432] [EC:1.11.1.9]
14776  Gpx2; glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
14778  Gpx3; glutathione peroxidase 3 [KO:K00432] [EC:1.11.1.9]
14780  Gpx5; glutathione peroxidase 5 [KO:K00432] [EC:1.11.1.9]
67305  Gpx7; glutathione peroxidase 7 [KO:K00432] [EC:1.11.1.9]
75512  Gpx6; glutathione peroxidase 6 [KO:K00432] [EC:1.11.1.9]
69590  Gpx8; glutathione peroxidase 8 (putative) [KO:K00432] [EC:1.11.1.9]
14782  Gsr; glutathione reductase [KO:K00383] [EC:1.8.1.7]
11657  Alb; albumin [KO:K16141]
22139  Ttr; transthyretin [KO:K20731]
331535  Serpina7; serine (or cysteine) peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 7 [KO:K20734]
14725  Lrp2; low density lipoprotein receptor-related protein 2 [KO:K06233]
Compound
C00001  H2O
C00005  NADPH
C00006  NADP+
C00007  Oxygen
C00027  Hydrogen peroxide
C00051  Glutathione
C00076  Calcium cation
C00092  D-Glucose 6-phosphate
C00117  D-Ribose 5-phosphate
C00127  Glutathione disulfide
C00165  Diacylglycerol
C00231  D-Xylulose 5-phosphate
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C00708  Iodide
C01060  3,5-Diiodo-L-tyrosine
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01829  Thyroxine
C02465  Triiodothyronine
C02515  3-Iodo-L-tyrosine
Reference
PMID:21448409
  Authors
Ahad F, Ganie SA
  Title
Iodine, Iodine metabolism and Iodine deficiency disorders revisited.
  Journal
Indian J Endocrinol Metab 14:13-7 (2010)
Reference
PMID:11717564
  Authors
Gillam MP, Kopp P
  Title
Genetic defects in thyroid hormone synthesis.
  Journal
Curr Opin Pediatr 13:364-72 (2001)
DOI:10.1097/00008480-200108000-00014
Reference
PMID:20167242
  Authors
Rokita SE, Adler JM, McTamney PM, Watson JA Jr
  Title
Efficient use and recycling of the micronutrient iodide in mammals.
  Journal
Biochimie 92:1227-35 (2010)
DOI:10.1016/j.biochi.2010.02.013
Reference
PMID:21683758
  Authors
Massart C, Hoste C, Virion A, Ruf J, Dumont JE, Van Sande J
  Title
Cell biology of H2O2 generation in the thyroid: investigation of the control of dual oxidases (DUOX) activity in intact ex vivo thyroid tissue and cell lines.
  Journal
Mol Cell Endocrinol 343:32-44 (2011)
DOI:10.1016/j.mce.2011.05.047
Reference
PMID:19196800
  Authors
Bizhanova A, Kopp P
  Title
Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid.
  Journal
Endocrinology 150:1084-90 (2009)
DOI:10.1210/en.2008-1437
Reference
PMID:21986207
  Authors
Fong P
  Title
Thyroid iodide efflux: a team effort?
  Journal
J Physiol 589:5929-39 (2011)
DOI:10.1113/jphysiol.2011.218594
Reference
PMID:17666482
  Authors
Song Y, Driessens N, Costa M, De Deken X, Detours V, Corvilain B, Maenhaut C, Miot F, Van Sande J, Many MC, Dumont JE
  Title
Roles of hydrogen peroxide in thyroid physiology and disease.
  Journal
J Clin Endocrinol Metab 92:3764-73 (2007)
DOI:10.1210/jc.2007-0660
Reference
PMID:11137035
  Authors
Kohn LD, Suzuki K, Nakazato M, Royaux I, Green ED
  Title
Effects of thyroglobulin and pendrin on iodide flux through the thyrocyte.
  Journal
Trends Endocrinol Metab 12:10-6 (2001)
DOI:10.1016/S1043-2760(00)00337-4
Reference
PMID:11029276
  Authors
Marino M, McCluskey RT
  Title
Role of thyroglobulin endocytic pathways in the control of thyroid hormone release.
  Journal
Am J Physiol Cell Physiol 279:C1295-306 (2000)
DOI:10.1152/ajpcell.2000.279.5.C1295
Reference
PMID:16870170
  Authors
Rivolta CM, Targovnik HM
  Title
Molecular advances in thyroglobulin disorders.
  Journal
Clin Chim Acta 374:8-24 (2006)
DOI:10.1016/j.cca.2006.05.043
Reference
PMID:10893432
  Authors
De La Vieja A, Dohan O, Levy O, Carrasco N
  Title
Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology.
  Journal
Physiol Rev 80:1083-105 (2000)
DOI:10.1152/physrev.2000.80.3.1083
Reference
PMID:20407074
  Authors
Ohye H, Sugawara M
  Title
Dual oxidase, hydrogen peroxide and thyroid diseases.
  Journal
Exp Biol Med (Maywood) 235:424-33 (2010)
DOI:10.1258/ebm.2009.009241
Reference
PMID:20093166
  Authors
Targovnik HM, Esperante SA, Rivolta CM
  Title
Genetics and phenomics of hypothyroidism and goiter due to thyroglobulin mutations.
  Journal
Mol Cell Endocrinol 322:44-55 (2010)
DOI:10.1016/j.mce.2010.01.009
Reference
PMID:20122987
  Authors
Grasberger H
  Title
Defects of thyroidal hydrogen peroxide generation in congenital hypothyroidism.
  Journal
Mol Cell Endocrinol 322:99-106 (2010)
DOI:10.1016/j.mce.2010.01.029
Reference
PMID:9086577
  Authors
Arvan P, Kim PS, Kuliawat R, Prabakaran D, Muresan Z, Yoo SE, Abu Hossain S
  Title
Intracellular protein transport to the thyrocyte plasma membrane: potential implications for thyroid physiology.
  Journal
Thyroid 7:89-105 (1997)
DOI:10.1089/thy.1997.7.89
Reference
PMID:15611820
  Authors
Vono-Toniolo J, Kopp P
  Title
Thyroglobulin gene mutations and other genetic defects associated with congenital hypothyroidism.
  Journal
Arq Bras Endocrinol Metabol 48:70-82 (2004)
DOI:10.1590/S0004-27302004000100009
Reference
PMID:23438835
  Authors
Vitale G, Salvioli S, Franceschi C
  Title
Oxidative stress and the ageing endocrine system.
  Journal
Nat Rev Endocrinol 9:228-40 (2013)
DOI:10.1038/nrendo.2013.29
Reference
PMID:20378719
  Authors
Calebiro D, Nikolaev VO, Lohse MJ
  Title
Imaging of persistent cAMP signaling by internalized G protein-coupled receptors.
  Journal
J Mol Endocrinol 45:1-8 (2010)
DOI:10.1677/JME-10-0014
Reference
PMID:9538302
  Authors
Newman CM, Price A, Davies DW, Gray TA, Weetman AP
  Title
Amiodarone and the thyroid: a practical guide to the management of thyroid dysfunction induced by amiodarone therapy.
  Journal
Heart 79:121-7 (1998)
DOI:10.1136/hrt.79.2.121
Related
pathway
mmu00350  Tyrosine metabolism
mmu00480  Glutathione metabolism
mmu04020  Calcium signaling pathway
mmu04142  Lysosome
mmu04146  Peroxisome
mmu04530  Tight junction
KO pathway
ko04918   
LinkDB

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