KEGG   PATHWAY: rno04918
Entry
rno04918                    Pathway                                
Name
Thyroid hormone synthesis - Rattus norvegicus (rat)
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
rno04918  Thyroid hormone synthesis
rno04918

Other DBs
GO: 0006590
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
25653  Tshb; thyrotropin subunit beta precursor [KO:K05251]
116700  Cga; glycoprotein hormones alpha chain precursor [KO:K08522]
25360  Tshr; thyrotropin receptor precursor [KO:K04249]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
499766  Ttf1; transcription termination factor 1 [KO:K15225]
295324  Ttf2; transcription termination factor 2 [KO:K15173] [EC:5.6.2.-]
81819  Pax8; paired box protein Pax-8 [KO:K09293]
81646  Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
81647  Atf2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
79255  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
310616  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform 1 [KO:K09048]
362165  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
362339  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
314638  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
500131  Creb5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
406169  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
24826  Tg; thyroglobulin isoform 2 precursor [KO:K10809]
25617  Hspa5; endoplasmic reticulum chaperone BiP precursor [KO:K09490] [EC:3.6.4.10]
362862  Hsp90b1; endoplasmin precursor [KO:K09487]
29144  Canx; calnexin precursor [KO:K08054]
116598  Pdia4; protein disulfide-isomerase A4 precursor [KO:K09582] [EC:5.3.4.1]
24210  Asgr1; asialoglycoprotein receptor 1 [KO:K10063]
29403  Asgr2; asialoglycoprotein receptor 2 [KO:K10064]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
114613  Slc5a5; sodium/iodide cotransporter [KO:K14385]
29440  Slc26a4; pendrin [KO:K14702]
54314  Tpo; thyroid peroxidase precursor [KO:K00431] [EC:1.11.1.8]
24211  Atp1a1; sodium/potassium-transporting ATPase subunit alpha-1 precursor [KO:K01539] [EC:7.2.2.13]
24212  Atp1a2; sodium/potassium-transporting ATPase subunit alpha-2 precursor [KO:K01539] [EC:7.2.2.13]
24213  Atp1a3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
29132  Atp1a4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
84396  Atp1b4; protein ATP1B4 [KO:K01540]
25650  Atp1b1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
24214  Atp1b2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
25390  Atp1b3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
29639  Fxyd2; sodium/potassium-transporting ATPase subunit gamma isoform a [KO:K01538]
308129  Iyd; iodotyrosine deiodinase 1 [KO:K17231] [EC:1.21.1.1]
499879  Duoxa2; dual oxidase maturation factor 2 [KO:K17232]
266807  Duox1; dual oxidase 1 precursor [KO:K13411] [EC:1.6.3.1 1.11.1.-]
79107  Duox2; dual oxidase 2 precursor [KO:K13411] [EC:1.6.3.1 1.11.1.-]
24404  Gpx1; glutathione peroxidase 1 [KO:K00432] [EC:1.11.1.9]
64317  Gpx3; glutathione peroxidase 3 precursor [KO:K00432] [EC:1.11.1.9]
259233  Gpx6; glutathione peroxidase 6 precursor [KO:K00432] [EC:1.11.1.9]
29326  Gpx2; glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
113919  Gpx5; epididymal secretory glutathione peroxidase precursor [KO:K00432] [EC:1.11.1.9]
298376  Gpx7; glutathione peroxidase 7 precursor [KO:K00432] [EC:1.11.1.9]
294744  Gpx8; probable glutathione peroxidase 8 [KO:K00432] [EC:1.11.1.9]
116686  Gsr; glutathione reductase [KO:K00383] [EC:1.8.1.7]
24186  Alb; albumin precursor [KO:K16141]
24856  Ttr; transthyretin precursor [KO:K20731]
81806  Serpina7; thyroxine-binding globulin precursor [KO:K20734]
29216  Lrp2; low-density lipoprotein receptor-related protein 2 precursor [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
rno00350  Tyrosine metabolism
rno00480  Glutathione metabolism
rno04020  Calcium signaling pathway
rno04142  Lysosome
rno04146  Peroxisome
rno04530  Tight junction
KO pathway
ko04918   
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