KEGG   PATHWAY: pps04918
Entry
pps04918                    Pathway                                
Name
Thyroid hormone synthesis - Pan paniscus (bonobo)
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
pps04918  Thyroid hormone synthesis
pps04918

Other DBs
GO: 0006590
Organism
Pan paniscus (bonobo) [GN:pps]
Gene
100967932  TSHB; thyrotropin subunit beta [KO:K05251]
100987945  CGA; glycoprotein hormones alpha chain [KO:K08522]
100972767  TSHR; thyrotropin receptor [KO:K04249]
100990650  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
117974231  neuroendocrine secretory protein 55 [KO:K04632]
100984585  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
100992014  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
100995134  ADCY3; adenylate cyclase type 3 isoform X4 [KO:K08043] [EC:4.6.1.1]
100978200  ADCY4; adenylate cyclase type 4 isoform X3 [KO:K08044] [EC:4.6.1.1]
100989177  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
100991116  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100984225  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100994715  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
100972356  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
100982589  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
100970917  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X5 [KO:K04345] [EC:2.7.11.11]
100968237  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100986730  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
100969660  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
100987524  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
100969344  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
100978643  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100967981  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100970296  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
100990245  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100973791  TTF1; transcription termination factor 1 isoform X1 [KO:K15225]
100975132  TTF2; transcription termination factor 2 isoform X2 [KO:K15173] [EC:5.6.2.-]
100988818  PAX8; paired box protein Pax-8 isoform X2 [KO:K09293]
100974672  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
100985706  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
100980724  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
100988487  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100986194  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
100981063  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100977804  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100989680  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100977358  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100973232  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
100993334  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
100990601  TG; thyroglobulin [KO:K10809]
100987715  HSPA5; endoplasmic reticulum chaperone BiP [KO:K09490] [EC:3.6.4.10]
100980415  HSP90B1; endoplasmin [KO:K09487]
100977183  LOW QUALITY PROTEIN: endoplasmin-like [KO:K09487]
103785804  LOW QUALITY PROTEIN: endoplasmin [KO:K09487]
100980239  CANX; calnexin isoform X1 [KO:K08054]
100970908  PDIA4; protein disulfide-isomerase A4 isoform X2 [KO:K09582] [EC:5.3.4.1]
100987509  ASGR1; asialoglycoprotein receptor 1 isoform X1 [KO:K10063]
100990332  ASGR2; asialoglycoprotein receptor 2 isoform X2 [KO:K10064]
100984884  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
100980378  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
100982024  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X6 [KO:K04960]
100971698  SLC5A5; sodium/iodide cotransporter [KO:K14385]
100992729  SLC26A4; pendrin [KO:K14702]
100996140  TPO; thyroid peroxidase isoform X1 [KO:K00431] [EC:1.11.1.8]
100968564  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
100968910  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 isoform X2 [KO:K01539] [EC:7.2.2.13]
100992562  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
100973141  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
100972401  ATP1B4; protein ATP1B4 isoform X2 [KO:K01540]
100981350  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 isoform X1 [KO:K01540]
100974727  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
100977407  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540]
103786316  sodium/potassium-transporting ATPase subunit gamma isoform X3 [KO:K01538]
100984862  IYD; iodotyrosine deiodinase 1 isoform X2 [KO:K17231] [EC:1.21.1.1]
100975828  DUOXA2; dual oxidase maturation factor 2 [KO:K17232]
100974723  DUOX1; dual oxidase 1 isoform X1 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
100978429  DUOX2; dual oxidase 2 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
100995983  GPX1; glutathione peroxidase 1 isoform X1 [KO:K00432] [EC:1.11.1.9]
100993851  GPX2; glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
100984958  GPX8; probable glutathione peroxidase 8 isoform X2 [KO:K00432] [EC:1.11.1.9]
100995148  GPX5; LOW QUALITY PROTEIN: epididymal secretory glutathione peroxidase [KO:K00432] [EC:1.11.1.9]
100995495  GPX6; glutathione peroxidase 6 [KO:K00432] [EC:1.11.1.9]
100995142  GPX3; glutathione peroxidase 3 [KO:K00432] [EC:1.11.1.9]
100967764  GPX7; glutathione peroxidase 7 [KO:K00432] [EC:1.11.1.9]
100977327  GSR; glutathione reductase, mitochondrial [KO:K00383] [EC:1.8.1.7]
100980638  ALB; serum albumin [KO:K16141]
100993568  TTR; transthyretin [KO:K20731]
100974005  SERPINA7; thyroxine-binding globulin isoform X2 [KO:K20734]
100982248  LRP2; low-density lipoprotein receptor-related protein 2 isoform X2 [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
pps00350  Tyrosine metabolism
pps00480  Glutathione metabolism
pps04020  Calcium signaling pathway
pps04142  Lysosome
pps04146  Peroxisome
pps04530  Tight junction
KO pathway
ko04918   

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Genome (1)   
   KEGG GENOME (1)   
Gene (79)   
   KEGG GENES (79)   
All databases (80)   

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