KEGG   PATHWAY: mdo04918
Entry
mdo04918                    Pathway                                
Name
Thyroid hormone synthesis - Monodelphis domestica (gray short-tailed opossum)
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
mdo04918  Thyroid hormone synthesis
mdo04918

Other DBs
GO: 0006590
Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
503501  TSHB; thyroid stimulating hormone beta [KO:K05251]
554198  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
100021427  TSHR; thyroid stimulating hormone receptor [KO:K04249]
100021523  GNAS; GNAS complex locus [KO:K04632]
100029582  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
100030463  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
100013164  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
100025332  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
100030872  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
100019274  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
100013823  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
100026554  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
100013831  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
100011211  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
100026861  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100032298  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100011605  GNAQ; G protein subunit alpha q [KO:K04634]
100033281  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
100031660  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
100031869  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
100031263  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
100024674  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
100013346  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
100017130  TTF1; transcription termination factor 1 [KO:K15225]
100010739  TTF2; transcription termination factor 2 [KO:K15173] [EC:5.6.2.-]
100026381  PAX8; paired box 8 [KO:K09293]
100014049  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
100025939  ATF2; activating transcription factor 2 [KO:K04450]
100012224  ATF4; activating transcription factor 4 [KO:K04374]
100017208  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
100020067  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
100022547  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
100015046  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
103104366  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
100032634  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
100025603  ATF6B; activating transcription factor 6 beta [KO:K09049]
100618718  TG; thyroglobulin [KO:K10809]
100015941  HSPA5; heat shock protein family A (Hsp70) member 5 [KO:K09490] [EC:3.6.4.10]
100014854  HSP90B1; heat shock protein 90 beta family member 1 [KO:K09487]
100028218  CANX; calnexin [KO:K08054]
100014120  PDIA4; protein disulfide isomerase family A member 4 [KO:K09582] [EC:5.3.4.1]
100016684  ASGR1; asialoglycoprotein receptor 1 [KO:K10063]
100013305  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100010212  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100025596  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100619880  SLC5A5; solute carrier family 5 member 5 [KO:K14385]
100010484  SLC26A4; solute carrier family 26 member 4 [KO:K14702]
100032350  TPO; thyroid peroxidase [KO:K00431] [EC:1.11.1.8]
100029759  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
100029754  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
100015422  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
100020118  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
100019139  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
100618619  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
107652422  FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
100032091  IYD; iodotyrosine deiodinase [KO:K17231] [EC:1.21.1.1]
100012704  DUOXA2; dual oxidase maturation factor 2 [KO:K17232]
100012836  DUOX1; dual oxidase 1 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
100012658  DUOX2; dual oxidase 2 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
100018504  GPX7; glutathione peroxidase 7 [KO:K00432] [EC:1.11.1.9]
100016887  GPX8; glutathione peroxidase 8 (putative) [KO:K00432] [EC:1.11.1.9]
100022680  GPX2; glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
100029378  GPX3; glutathione peroxidase 3 [KO:K00432] [EC:1.11.1.9]
100619791  GPX1; glutathione peroxidase 1 [KO:K00432] [EC:1.11.1.9]
100019810  GSR; glutathione-disulfide reductase [KO:K00383] [EC:1.8.1.7]
100014917  ALB; albumin [KO:K16141]
497043  TTR; transthyretin [KO:K20731]
100024653  thyroxine-binding globulin-like [KO:K20734]
100024150  LRP2; LDL 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
  Authors
Ahad F, Ganie SA
  Title
Iodine, Iodine metabolism and Iodine deficiency disorders revisited.
  Journal
Indian J Endocrinol Metab 14:13-7 (2010)
Reference
  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
  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
  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
  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
  Authors
Fong P
  Title
Thyroid iodide efflux: a team effort?
  Journal
J Physiol 589:5929-39 (2011)
DOI:10.1113/jphysiol.2011.218594
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
mdo00350  Tyrosine metabolism
mdo00480  Glutathione metabolism
mdo04020  Calcium signaling pathway
mdo04142  Lysosome
mdo04146  Peroxisome
mdo04530  Tight junction
KO pathway
ko04918   
LinkDB

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