KEGG   PATHWAY: umr04918
Entry
umr04918                    Pathway                                
Name
Thyroid hormone synthesis - Ursus maritimus (polar bear)
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
umr04918  Thyroid hormone synthesis
umr04918

Other DBs
GO: 0006590
Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103656576  DUOXA2; dual oxidase maturation factor 2 isoform X1 [KO:K17232]
103656587  DUOX2; LOW QUALITY PROTEIN: dual oxidase 2 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
103656588  DUOX1; LOW QUALITY PROTEIN: dual oxidase 1 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
103656729  TG; thyroglobulin [KO:K10809]
103658932  [KO:K09047]
103659081  GSR; glutathione reductase, mitochondrial [KO:K00383] [EC:1.8.1.7]
103659385  TPO; thyroid peroxidase isoform X1 [KO:K00431] [EC:1.11.1.8]
103659593  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
103659748  CGA; glycoprotein hormones alpha chain [KO:K08522]
103659802  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
103659884  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
103660367  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
103660460  [KO:K10064]
103661704  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103662972  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
103663250  TTR; transthyretin [KO:K20731]
103663281  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103663677  GPX8; probable glutathione peroxidase 8 isoform X1 [KO:K00432] [EC:1.11.1.9]
103664585  GPX3; glutathione peroxidase 3 [KO:K00432] [EC:1.11.1.9]
103665275  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103665303  ALB; albumin isoform X2 [KO:K16141]
103665553  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103665907  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103666913  IYD; iodotyrosine deiodinase 1 [KO:K17231] [EC:1.21.1.1]
103667087  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
103668409  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
103668547  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103668895  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
103668925  SERPINA7; thyroxine-binding globulin [KO:K20734]
103669052  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
103669067  PDIA4; protein disulfide-isomerase A4 [KO:K09582] [EC:5.3.4.1]
103669178  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
103669413  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
103669418  TSHB; thyrotropin subunit beta [KO:K05251]
103669597  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103670252  TTF1; transcription termination factor 1 [KO:K15225]
103670323  HSPA5; endoplasmic reticulum chaperone BiP [KO:K09490] [EC:3.6.4.10]
103670618  TSHR; thyrotropin receptor [KO:K04249]
103670709  GPX7; glutathione peroxidase 7 isoform X1 [KO:K00432] [EC:1.11.1.9]
103670935  [KO:K04632]
103670936  [KO:K04632]
103671685  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103671861  PAX8; paired box protein Pax-8 [KO:K09293]
103672049  [KO:K01539] [EC:7.2.2.13]
103672113  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
103672204  GPX2; glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
103672393  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103672914  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103673552  [KO:K05858] [EC:3.1.4.11]
103673916  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
103674425  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103674426  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
103674675  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103674706  SLC26A4; pendrin [KO:K14702]
103675099  GPX1; glutathione peroxidase 1 [KO:K00432] [EC:1.11.1.9]
103675166  SLC5A5; sodium/iodide cotransporter [KO:K14385]
103675618  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
103676372  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103676491  HSP90B1; endoplasmin [KO:K09487]
103678432  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
103678826  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
103679250  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
103679331  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
103679549  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
103679986  CANX; calnexin [KO:K08054]
103680185  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
103680217  ATP1B4; protein ATP1B4 [KO:K01540]
103680861  TTF2; transcription termination factor 2 [KO:K15173] [EC:5.6.2.-]
103681679  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
103681951  GPX5; epididymal secretory glutathione peroxidase isoform X1 [KO:K00432] [EC:1.11.1.9]
103681952  GPX6; glutathione peroxidase 6 [KO:K00432] [EC:1.11.1.9]
103682183  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103682282  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
121099746  [KO:K05858] [EC:3.1.4.11]
121102415  [KO:K10063]
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
umr00350  Tyrosine metabolism
umr00480  Glutathione metabolism
umr04020  Calcium signaling pathway
umr04142  Lysosome
umr04146  Peroxisome
umr04530  Tight junction
KO pathway
ko04918   

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