KEGG   PATHWAY: eai04925
Entry
eai04925                    Pathway                                
Name
Aldosterone synthesis and secretion - Equus asinus (ass)
Description
Aldosterone is a steroid hormone synthesized in and secreted from the outer layer of the adrenal cortex, the zona glomerulosa. Aldosterone plays an important role in the regulation of systemic blood pressure through the absorption of sodium and water. Angiotensin II (Ang II), potassium (K+) and adrenocorticotropin (ACTH) are the main extracellular stimuli which regulate aldosterone secretion. These physiological agonists all converge on two major intracellular signaling pathways: calcium (Ca2+) mobilization and an increase in cAMP production. The increase in cytosolic calcium levels activates calcium/calmodulin- dependent protein kinases (CaMK), and the increased cAMP levels stimulate the activity of cAMP-dependent protein kinase, or protein kinase A (PKA). The activated CaMK, and possibly PKA, activates transcription factors (NURR1 and NGF1B, CREB) to induce StAR and CYP11B2 expression, the early and late rate- limiting steps in aldosterone biosynthesis, respectively, thereby stimulating aldosterone secretion.
Class
Organismal Systems; Endocrine system
Pathway map
eai04925  Aldosterone synthesis and secretion
eai04925

Other DBs
GO: 0035932
Organism
Equus asinus (ass) [GN:eai]
Gene
106844922  AGT; angiotensinogen [KO:K09821]
106829436  AGTR1; type-1 angiotensin II receptor [KO:K04166]
106825688  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
106832309  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
106823182  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
106823191  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
106835172  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
106833627  PLCB3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
106848450  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
106834887  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
106834634  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
106835567  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
106823831  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
106840859  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
106826113  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
106845140  PRKD2; serine/threonine-protein kinase D2 [KO:K06070] [EC:2.7.11.13]
106825855  PRKD3; serine/threonine-protein kinase D3 isoform X1 [KO:K06070] [EC:2.7.11.13]
106847867  PRKD1; serine/threonine-protein kinase D1 isoform X1 [KO:K06070] [EC:2.7.11.13]
106828159  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
106837905  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X2 [KO:K04450]
106842437  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
106846249  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X2 [KO:K09048]
106843990  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
106846981  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
106829982  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
106832323  CREB3L3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
106831046  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
106831009  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
106845044  ATF1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
106847577  DAGLA; diacylglycerol lipase-alpha [KO:K13806] [EC:3.1.1.116]
106840517  DAGLB; diacylglycerol lipase-beta [KO:K13806] [EC:3.1.1.116]
106832676  KCNK3; potassium channel subfamily K member 3 [KO:K04914]
106828681  KCNK9; potassium channel subfamily K member 9 [KO:K04919]
106845695  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
106847933  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
106835689  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform X2 [KO:K01539] [EC:7.2.2.13]
106835754  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 isoform X1 [KO:K01539] [EC:7.2.2.13]
106835755  sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
106824855  ATP1B4; protein ATP1B4 isoform X3 [KO:K01540]
106841565  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
106844216  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 isoform X1 [KO:K01540]
106838143  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
106826471  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
106836269  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H isoform X1 [KO:K04855]
106842428  CACNA1I; LOW QUALITY PROTEIN: voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
106839455  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
106822066  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X8 [KO:K04851]
106826963  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
106823553  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X3 [KO:K04857]
106842218  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
106845168  CALM3; calmodulin-3 [KO:K02183]
106845190  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
106833785  CALML5; calmodulin-like protein 5 [KO:K02183]
106833786  calmodulin-like protein 3 [KO:K02183]
106825365  CALM1; calmodulin-1 [KO:K02183]
106847177  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
106826025  CALM2; calmodulin-2 [KO:K02183]
106827198  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G isoform X2 [KO:K08794] [EC:2.7.11.17]
106835609  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X1 [KO:K08794] [EC:2.7.11.17]
106836930  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X5 [KO:K08794] [EC:2.7.11.17]
106843233  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
106843543  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
106822866  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
106838495  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
106832342  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
106835630  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
106826650  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
106845648  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
106824024  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
106847941  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
106846613  LDLR; LOW QUALITY PROTEIN: low-density lipoprotein receptor [KO:K12473]
106844877  SCARB1; scavenger receptor class B member 1 isoform X2 [KO:K13885]
106841107  POMC; pro-opiomelanocortin [KO:K05228]
106828648  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
106825087  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
106825115  neuroendocrine secretory protein 55 [KO:K04632]
106822932  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
106823001  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
106841140  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
106848607  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
106823728  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
106836825  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
106824126  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
106824833  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
106826021  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
106844316  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
106824036  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
106824666  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
106841970  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
106835239  NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465]
106842692  cholesterol side-chain cleavage enzyme, mitochondrial [KO:K00498] [EC:1.14.15.6]
106832920  HSD3B2; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
106831008  steroid 21-hydroxylase [KO:K00513] [EC:1.14.14.16]
106836709  NPPA; natriuretic peptides A [KO:K12334]
106846257  NPR1; atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
106831663  PDE2A; cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X1 [KO:K18283] [EC:3.1.4.17]
Compound
C00003  NAD+
C00004  NADH
C00005  NADPH
C00006  NADP+
C00020  AMP
C00076  Calcium cation
C00165  Diacylglycerol
C00187  Cholesterol
C00219  Arachidonate
C00238  Potassium cation
C00410  Progesterone
C00575  3',5'-Cyclic AMP
C00942  3',5'-Cyclic GMP
C01124  18-Hydroxycorticosterone
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01780  Aldosterone
C01953  Pregnenolone
C02140  Corticosterone
C03205  11-Deoxycorticosterone
C14777  12(S)-HETE
C14822  12(R)-HETE
Reference
PMID:21839803
  Authors
Hattangady NG, Olala LO, Bollag WB, Rainey WE
  Title
Acute and chronic regulation of aldosterone production.
  Journal
Mol Cell Endocrinol 350:151-62 (2012)
DOI:10.1016/j.mce.2011.07.034
Reference
PMID:24944029
  Authors
Bollag WB
  Title
Regulation of aldosterone synthesis and secretion.
  Journal
Compr Physiol 4:1017-55 (2014)
DOI:10.1002/cphy.c130037
Reference
PMID:15044681
  Authors
Spat A, Hunyady L
  Title
Control of aldosterone secretion: a model for convergence in cellular signaling pathways.
  Journal
Physiol Rev 84:489-539 (2004)
DOI:10.1152/physrev.00030.2003
Reference
PMID:18406824
  Authors
Boon WC, Coghlan JP, Curnow KM, McDougall JG
  Title
Aldosterone secretion: a molecular perspective.
  Journal
Trends Endocrinol Metab 8:346-54 (1997)
DOI:10.1016/S1043-2760(97)00136-7
Reference
PMID:14645496
  Authors
Bassett MH, Suzuki T, Sasano H, White PC, Rainey WE
  Title
The orphan nuclear receptors NURR1 and NGFIB regulate adrenal aldosterone production.
  Journal
Mol Endocrinol 18:279-90 (2004)
DOI:10.1210/me.2003-0005
Reference
PMID:22689262
  Authors
Guagliardo NA, Yao J, Hu C, Barrett PQ
  Title
Minireview: aldosterone biosynthesis: electrically gated for our protection.
  Journal
Endocrinology 153:3579-86 (2012)
DOI:10.1210/en.2012-1339
Reference
PMID:22364774
  Authors
Spat A, Fulop L, Szanda G
  Title
The role of mitochondrial Ca(2+) and NAD(P)H in the control of aldosterone secretion.
  Journal
Cell Calcium 52:64-72 (2012)
DOI:10.1016/j.ceca.2012.01.009
Reference
PMID:22395411
  Authors
Spat A, Szanda G
  Title
Special features of mitochondrial Ca(2)(+) signalling in adrenal glomerulosa cells.
  Journal
Pflugers Arch 464:43-50 (2012)
DOI:10.1007/s00424-012-1086-y
Reference
PMID:21962440
  Authors
Tsai LC, Beavo JA
  Title
The roles of cyclic nucleotide phosphodiesterases (PDEs) in steroidogenesis.
  Journal
Curr Opin Pharmacol 11:670-5 (2011)
DOI:10.1016/j.coph.2011.09.003
Reference
PMID:10536682
  Authors
Delcayre C, Silvestre JS
  Title
Aldosterone and the heart: towards a physiological function?
  Journal
Cardiovasc Res 43:7-12 (1999)
DOI:10.1016/S0008-6363(99)00088-7
Reference
PMID:15026188
  Authors
Lisurek M, Bernhardt R
  Title
Modulation of aldosterone and cortisol synthesis on the molecular level.
  Journal
Mol Cell Endocrinol 215:149-59 (2004)
DOI:10.1016/j.mce.2003.11.008
Reference
PMID:23628605
  Authors
Miller WL
  Title
Steroid hormone synthesis in mitochondria.
  Journal
Mol Cell Endocrinol 379:62-73 (2013)
DOI:10.1016/j.mce.2013.04.014
Reference
PMID:25788893
  Authors
Martinez-Arguelles DB, Papadopoulos V
  Title
Mechanisms mediating environmental chemical-induced endocrine disruption in the adrenal gland.
  Journal
Front Endocrinol (Lausanne) 6:29 (2015)
DOI:10.3389/fendo.2015.00029
Related
pathway
eai00140  Steroid hormone biosynthesis
eai00590  Arachidonic acid metabolism
eai04020  Calcium signaling pathway
eai04022  cGMP-PKG signaling pathway
eai04024  cAMP signaling pathway
eai04614  Renin-angiotensin system
eai04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   
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