KEGG   PATHWAY: ocu04918
Entry
ocu04918                    Pathway                                
Name
Thyroid hormone synthesis - Oryctolagus cuniculus (rabbit)
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
ocu04918  Thyroid hormone synthesis
ocu04918

Other DBs
GO: 0006590
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100302414  TSHB; thyrotropin subunit beta precursor [KO:K05251]
100009481  CGA; glycoprotein hormones alpha chain precursor [KO:K08522]
100353965  thyrotropin receptor isoform X1 [KO:K04249]
100008904  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
100346323  neuroendocrine secretory protein 55 [KO:K04632]
103347035  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100009201  adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
100343958  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
100346742  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100009315  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100354934  adenylate cyclase type 6 isoform X8 [KO:K08046] [EC:4.6.1.1]
100357357  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100337882  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
100340877  adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
100008815  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100342212  cAMP-dependent protein kinase catalytic subunit beta isoform X3 [KO:K04345] [EC:2.7.11.11]
100340719  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100348672  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
100350395  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100341512  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
103347536  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100037720  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100037719  PRKCB; protein kinase C beta type isoform I [KO:K19662] [EC:2.7.11.13]
100009102  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100358824  transcription termination factor 1 isoform X1 [KO:K15225]
100340161  transcription termination factor 2 isoform X1 [KO:K15173] [EC:5.6.2.-]
100356013  paired box protein Pax-8 isoform X1 [KO:K09293]
100351999  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100355367  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
100339383  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100358175  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100343130  cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X2 [KO:K09048]
100345475  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
100357876  cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
100357483  cyclic AMP-responsive element-binding protein 5 isoform X3 [KO:K09047]
100357489  cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
127493063  cyclic AMP-dependent transcription factor ATF-6 beta-like isoform X1 [KO:K09049]
100339135  thyroglobulin [KO:K10809]
100008764  endoplasmic reticulum chaperone BiP [KO:K09490] [EC:3.6.4.10]
100009456  endoplasmin [KO:K09487]
100341645  calnexin [KO:K08054]
100354026  protein disulfide-isomerase A4 isoform X1 [KO:K09582] [EC:5.3.4.1]
127491672  protein disulfide-isomerase A4 [KO:K09582] [EC:5.3.4.1]
100346913  asialoglycoprotein receptor 1 isoform X1 [KO:K10063]
100347178  asialoglycoprotein receptor 2 [KO:K10064]
100009505  inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100356806  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100008939  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
100345415  pendrin [KO:K14702]
100358662  thyroid peroxidase [KO:K00431] [EC:1.11.1.8]
127486836  thyroid peroxidase-like [KO:K00431] [EC:1.11.1.8]
100349382  sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
100358269  sodium/potassium-transporting ATPase subunit alpha-4 isoform X1 [KO:K01539] [EC:7.2.2.13]
100008756  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
100302415  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
100009577  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
100008749  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
100008788  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
100350113  protein ATP1B4 isoform X2 [KO:K01540]
103349229  sodium/potassium-transporting ATPase subunit gamma isoform X2 [KO:K01538]
127482585  sodium/potassium-transporting ATPase subunit gamma-like isoform X1 [KO:K01538]
127492945  iodotyrosine deiodinase 1 isoform X1 [KO:K17231] [EC:1.21.1.1]
100353029  iodotyrosine deiodinase 1 [KO:K17231] [EC:1.21.1.1]
100355642  dual oxidase maturation factor 2 [KO:K17232]
100345610  dual oxidase 2 isoform X1 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
100344845  dual oxidase 1 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
100346543  probable glutathione peroxidase 8 isoform X1 [KO:K00432] [EC:1.11.1.9]
100355382  GPX7; glutathione peroxidase 7 precursor [KO:K00432] [EC:1.11.1.9]
100341099  GPX6; glutathione peroxidase 6 precursor [KO:K00432] [EC:1.11.1.9]
100355002  GPX2; glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
100343289  GPX3; glutathione peroxidase 3 precursor [KO:K00432] [EC:1.11.1.9]
100009258  GPX1; glutathione peroxidase 1 [KO:K00432] [EC:1.11.1.9]
100346804  GPX5; epididymal secretory glutathione peroxidase isoform X1 [KO:K00432] [EC:1.11.1.9]
100337794  glutathione reductase, mitochondrial isoform X1 [KO:K00383] [EC:1.8.1.7]
100009195  ALB; albumin precursor [KO:K16141]
100347317  transthyretin [KO:K20731]
100351289  thyroxine-binding globulin [KO:K20734]
100346275  low-density lipoprotein receptor-related protein 2 isoform X3 [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
ocu00350  Tyrosine metabolism
ocu00480  Glutathione metabolism
ocu04020  Calcium signaling pathway
ocu04142  Lysosome
ocu04146  Peroxisome
ocu04530  Tight junction
KO pathway
ko04918   
LinkDB

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