KEGG   PATHWAY: mcc04918
Entry
mcc04918                    Pathway                                
Name
Thyroid hormone synthesis - Macaca mulatta (rhesus monkey)
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
mcc04918  Thyroid hormone synthesis
mcc04918

Other DBs
GO: 0006590
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
709374  TSHB; thyrotropin subunit beta [KO:K05251]
697859  CGA; glycoprotein hormones alpha chain [KO:K08522]
574251  TSHR; thyrotropin receptor precursor [KO:K04249]
694289  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
100424899  neuroendocrine secretory protein 55 [KO:K04632]
697230  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
695328  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
693523  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
714684  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
715897  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
707978  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
694730  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
695792  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
706789  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
709728  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
718632  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
700652  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
705680  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
701951  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
718418  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
718387  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
717764  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
718412  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
701195  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
720263  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
715002  TTF1; transcription termination factor 1 [KO:K15225]
711312  TTF2; transcription termination factor 2 [KO:K15173] [EC:5.6.2.-]
701906  PAX8; paired box protein Pax-8 isoform X6 [KO:K09293]
708717  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
699072  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
703965  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
714981  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
713391  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
696350  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
721825  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
715951  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
697718  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
717050  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
701756  TG; thyroglobulin [KO:K10809]
703193  HSPA5; 78 kDa glucose-regulated protein precursor [KO:K09490] [EC:3.6.4.10]
699568  HSP90B1; endoplasmin precursor [KO:K09487]
704794  CANX; calnexin isoform X2 [KO:K08054]
709716  PDIA4; protein disulfide-isomerase A4 [KO:K09582] [EC:5.3.4.1]
721786  ASGR1; asialoglycoprotein receptor 1 isoform X1 [KO:K10063]
721779  ASGR2; asialoglycoprotein receptor 2 isoform X1 [KO:K10064]
703669  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
708714  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
718040  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
720060  SLC5A5; sodium/iodide cotransporter [KO:K14385]
699859  SLC26A4; pendrin [KO:K14702]
721610  TPO; thyroid peroxidase [KO:K00431] [EC:1.11.1.8]
710368  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
720191  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
706513  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
719623  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 isoform X1 [KO:K01539] [EC:7.2.2.13]
716093  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
700443  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
696160  ATP1B4; protein ATP1B4 [KO:K01540]
716682  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
704049  sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
705471  IYD; iodotyrosine deiodinase 1 isoform X1 [KO:K17231] [EC:1.21.1.1]
712992  DUOXA2; dual oxidase maturation factor 2 [KO:K17232]
713126  DUOX1; dual oxidase 1 isoform X2 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
713906  DUOX2; dual oxidase 2 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
708014  GPX5; epididymal secretory glutathione peroxidase precursor [KO:K00432] [EC:1.11.1.9]
715474  GPX7; glutathione peroxidase 7 precursor [KO:K00432] [EC:1.11.1.9]
708429  GPX2; glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
706732  GPX1; glutathione peroxidase 1 [KO:K00432] [EC:1.11.1.9]
100286832  GPX6; glutathione peroxidase 6 precursor [KO:K00432] [EC:1.11.1.9]
713057  GPX3; glutathione peroxidase 3 precursor [KO:K00432] [EC:1.11.1.9]
705965  GPX8; probable glutathione peroxidase 8 isoform X2 [KO:K00432] [EC:1.11.1.9]
100425521  GSR; glutathione reductase, mitochondrial [KO:K00383] [EC:1.8.1.7]
704892  ALB; serum albumin precursor [KO:K16141]
705943  TTR; transthyretin precursor [KO:K20731]
700439  SERPINA7; thyroxine-binding globulin isoform X1 [KO:K20734]
705786  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
mcc00350  Tyrosine metabolism
mcc00480  Glutathione metabolism
mcc04020  Calcium signaling pathway
mcc04142  Lysosome
mcc04146  Peroxisome
mcc04530  Tight junction
KO pathway
ko04918   
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