KEGG   PATHWAY: mna04918
mna04918                    Pathway                                

Thyroid hormone synthesis - Miniopterus natalensis
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.
Organismal Systems; Endocrine system
Pathway map
mna04918  Thyroid hormone synthesis

Other DBs
GO: 0006590
Miniopterus natalensis [GN:mna]
107545279  TSHB; thyrotropin subunit beta [KO:K05251]
107532807  CGA; glycoprotein hormones alpha chain [KO:K08522]
107542654  TSHR; thyrotropin receptor [KO:K04249]
107529329  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
107529353  neuroendocrine secretory protein 55-like [KO:K04632]
107526004  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
107540528  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:]
107534062  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:]
107531740  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:]
107527242  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:]
107528232  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:]
107531029  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:]
107539500  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
107535777  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:]
107544336  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
107543188  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
107544926  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107542967  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:]
107536366  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:]
107536369  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:]
107539797  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:]
107538300  PRKCA; protein kinase C alpha type [KO:K02677] [EC:]
107544745  PRKCB; protein kinase C beta type [KO:K19662] [EC:]
107540426  PRKCG; protein kinase C gamma type [KO:K19663] [EC:]
107524635  TTF1; transcription termination factor 1 [KO:K15225]
107545304  TTF2; transcription termination factor 2 [KO:K15173] [EC:3.6.4.-]
107528648  PAX8; paired box protein Pax-8 isoform X1 [KO:K09293]
107524712  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
107532468  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
107531265  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
107525737  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
107543873  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
107530327  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
107544136  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
107544933  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
107544390  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
107539006  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
107539491  TG; thyroglobulin [KO:K10809]
107535485  HSPA5; 78 kDa glucose-regulated protein [KO:K09490] [EC:]
107545155  HSP90B1; endoplasmin [KO:K09487]
107528428  CANX; calnexin [KO:K08054]
107523800  PDIA4; protein disulfide-isomerase A4 [KO:K09582] [EC:]
107544250  ASGR1; asialoglycoprotein receptor 1 [KO:K10063]
107544247  asialoglycoprotein receptor 2-like [KO:K10064]
107529142  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
107525255  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
107541588  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
107535368  SLC5A5; sodium/iodide cotransporter [KO:K14385]
107526616  SLC26A4; pendrin [KO:K14702]
107526670  TPO; thyroid peroxidase [KO:K00431] [EC:]
107545330  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:]
107538456  sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:]
107534181  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:]
107537932  ATP1B4; protein ATP1B4 isoform X1 [KO:K01540]
107534704  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
107534499  sodium/potassium-transporting ATPase subunit beta-3-like [KO:K01540]
107529056  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
107544529  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
107530783  FXYD2; sodium/potassium-transporting ATPase subunit gamma [KO:K01538]
107535960  IYD; iodotyrosine deiodinase 1 isoform X1 [KO:K17231] [EC:]
107536164  DUOXA2; dual oxidase maturation factor 2 [KO:K17232]
107536153  DUOX1; dual oxidase 1 [KO:K13411] [EC: 1.11.1.-]
107536249  DUOX2; dual oxidase 2 [KO:K13411] [EC: 1.11.1.-]
107537976  GPX3; glutathione peroxidase 3 [KO:K00432] [EC:]
107545682  GPX2; glutathione peroxidase 2 [KO:K00432] [EC:]
107543157  epididymal secretory glutathione peroxidase-like [KO:K00432] [EC:]
107527162  GPX8; probable glutathione peroxidase 8 isoform X1 [KO:K00432] [EC:]
107529364  GPX1; glutathione peroxidase 1 [KO:K00432] [EC:]
107535405  GPX7; glutathione peroxidase 7 [KO:K00432] [EC:]
107534101  GSR; glutathione reductase, mitochondrial [KO:K00383] [EC:]
107534491  serum albumin-like [KO:K16141]
107534492  ALB; serum albumin [KO:K16141]
107524205  TTR; transthyretin [KO:K20731]
107532136  SERPINA7; thyroxine-binding globulin [KO:K20734]
107546254  LRP2; low-density lipoprotein receptor-related protein 2 [KO:K06233]
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
Ahad F, Ganie SA
Iodine, Iodine metabolism and Iodine deficiency disorders revisited.
Indian J Endocrinol Metab 14:13-7 (2010)
Gillam MP, Kopp P
Genetic defects in thyroid hormone synthesis.
Curr Opin Pediatr 13:364-72 (2001)
Rokita SE, Adler JM, McTamney PM, Watson JA Jr
Efficient use and recycling of the micronutrient iodide in mammals.
Biochimie 92:1227-35 (2010)
Massart C, Hoste C, Virion A, Ruf J, Dumont JE, Van Sande J
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.
Mol Cell Endocrinol 343:32-44 (2011)
Bizhanova A, Kopp P
Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid.
Endocrinology 150:1084-90 (2009)
Fong P
Thyroid iodide efflux: a team effort?
J Physiol 589:5929-39 (2011)
Song Y, Driessens N, Costa M, De Deken X, Detours V, Corvilain B, Maenhaut C, Miot F, Van Sande J, Many MC, Dumont JE
Roles of hydrogen peroxide in thyroid physiology and disease.
J Clin Endocrinol Metab 92:3764-73 (2007)
Kohn LD, Suzuki K, Nakazato M, Royaux I, Green ED
Effects of thyroglobulin and pendrin on iodide flux through the thyrocyte.
Trends Endocrinol Metab 12:10-6 (2001)
Marino M, McCluskey RT
Role of thyroglobulin endocytic pathways in the control of thyroid hormone release.
Am J Physiol Cell Physiol 279:C1295-306 (2000)
Rivolta CM, Targovnik HM
Molecular advances in thyroglobulin disorders.
Clin Chim Acta 374:8-24 (2006)
De La Vieja A, Dohan O, Levy O, Carrasco N
Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology.
Physiol Rev 80:1083-105 (2000)
Ohye H, Sugawara M
Dual oxidase, hydrogen peroxide and thyroid diseases.
Exp Biol Med (Maywood) 235:424-33 (2010)
Targovnik HM, Esperante SA, Rivolta CM
Genetics and phenomics of hypothyroidism and goiter due to thyroglobulin mutations.
Mol Cell Endocrinol 322:44-55 (2010)
Grasberger H
Defects of thyroidal hydrogen peroxide generation in congenital hypothyroidism.
Mol Cell Endocrinol 322:99-106 (2010)
Arvan P, Kim PS, Kuliawat R, Prabakaran D, Muresan Z, Yoo SE, Abu Hossain S
Intracellular protein transport to the thyrocyte plasma membrane: potential implications for thyroid physiology.
Thyroid 7:89-105 (1997)
Vono-Toniolo J, Kopp P
Thyroglobulin gene mutations and other genetic defects associated with congenital hypothyroidism.
Arq Bras Endocrinol Metabol 48:70-82 (2004)
Vitale G, Salvioli S, Franceschi C
Oxidative stress and the ageing endocrine system.
Nat Rev Endocrinol 9:228-40 (2013)
Calebiro D, Nikolaev VO, Lohse MJ
Imaging of persistent cAMP signaling by internalized G protein-coupled receptors.
J Mol Endocrinol 45:1-8 (2010)
Newman CM, Price A, Davies DW, Gray TA, Weetman AP
Amiodarone and the thyroid: a practical guide to the management of thyroid dysfunction induced by amiodarone therapy.
Heart 79:121-7 (1998)
mna00350  Tyrosine metabolism
mna00480  Glutathione metabolism
mna04020  Calcium signaling pathway
mna04142  Lysosome
mna04146  Peroxisome
mna04530  Tight junction
KO pathway

DBGET integrated database retrieval system