KEGG   PATHWAY: mleu04918
Entry
mleu04918                   Pathway                                
Name
Thyroid hormone synthesis - Mandrillus leucophaeus (drill)
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
mleu04918  Thyroid hormone synthesis
mleu04918

Other DBs
GO: 0006590
Organism
Mandrillus leucophaeus (drill) [GN:mleu]
Gene
105554361  TSHB; thyrotropin subunit beta [KO:K05251]
105545831  CGA; glycoprotein hormones alpha chain isoform X1 [KO:K08522]
105531719  TSHR; thyrotropin receptor isoform X1 [KO:K04249]
105548339  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
105548340  neuroendocrine secretory protein 55 [KO:K04632]
105541972  uncharacterized protein LOC105541972 [KO:K08041] [EC:4.6.1.1]
105535662  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105534027  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
105532738  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105533183  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105544918  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105545643  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
105530895  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
105541508  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105532068  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
105540992  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105538055  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105542500  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105546224  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105552818  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105553023  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
105549095  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
105548239  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
105545146  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
105539692  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
105531595  TTF1; transcription termination factor 1 [KO:K15225]
105554385  TTF2; transcription termination factor 2 [KO:K15173] [EC:5.6.2.-]
105533664  paired box protein Pax-8-like [KO:K09293]
105530462  PAX8; paired box protein Pax-8 [KO:K09293]
105549382  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105548041  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
105538852  ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374]
105539715  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105554054  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
105554841  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105530028  CREB3L3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105550535  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105533710  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105531497  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
105537484  TG; thyroglobulin [KO:K10809]
105545670  HSPA5; 78 kDa glucose-regulated protein [KO:K09490] [EC:3.6.4.10]
105536204  HSP90B1; endoplasmin [KO:K09487]
105537285  CANX; calnexin isoform X1 [KO:K08054]
105546369  PDIA4; protein disulfide-isomerase A4 [KO:K09582] [EC:5.3.4.1]
105549908  ASGR1; asialoglycoprotein receptor 1 [KO:K10063]
105549909  ASGR2; asialoglycoprotein receptor 2 isoform X1 [KO:K10064]
105528641  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105555461  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105544182  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
105547559  SLC5A5; sodium/iodide cotransporter [KO:K14385]
105544094  SLC26A4; pendrin [KO:K14702]
105546350  TPO; thyroid peroxidase [KO:K00431] [EC:1.11.1.8]
105532275  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
105532277  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 isoform X1 [KO:K01539] [EC:7.2.2.13]
105554375  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform X1 [KO:K01539] [EC:7.2.2.13]
105542535  ATP1A3; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-3 [KO:K01539] [EC:7.2.2.13]
105539598  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 isoform X1 [KO:K01540]
105555629  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
105549867  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
105537539  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
105528204  FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538]
105545702  IYD; iodotyrosine dehalogenase 1 isoform X1 [KO:K17231] [EC:1.21.1.1]
105548191  DUOXA2; dual oxidase maturation factor 2 [KO:K17232]
105548205  DUOX2; dual oxidase 2 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
105548207  DUOX1; dual oxidase 1 [KO:K13411] [EC:1.6.3.1 1.11.1.-]
105538447  GPX2; LOW QUALITY PROTEIN: glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
105551503  GPX8; probable glutathione peroxidase 8 isoform X1 [KO:K00432] [EC:1.11.1.9]
105540354  GPX1; LOW QUALITY PROTEIN: glutathione peroxidase 1 [KO:K00432] [EC:1.11.1.9]
105547609  GPX6; LOW QUALITY PROTEIN: glutathione peroxidase 6 [KO:K00432] [EC:1.11.1.9]
105547610  GPX5; epididymal secretory glutathione peroxidase isoform X1 [KO:K00432] [EC:1.11.1.9]
105534944  GPX7; glutathione peroxidase 7 [KO:K00432] [EC:1.11.1.9]
105543416  GPX3; LOW QUALITY PROTEIN: glutathione peroxidase 3 [KO:K00432] [EC:1.11.1.9]
105538000  GSR; LOW QUALITY PROTEIN: glutathione reductase, mitochondrial [KO:K00383] [EC:1.8.1.7]
105531141  ALB; serum albumin [KO:K16141]
105535337  TTR; transthyretin [KO:K20731]
105536380  SERPINA7; thyroxine-binding globulin [KO:K20734]
105545287  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
mleu00350  Tyrosine metabolism
mleu00480  Glutathione metabolism
mleu04020  Calcium signaling pathway
mleu04142  Lysosome
mleu04146  Peroxisome
mleu04530  Tight junction
KO pathway
ko04918   
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