KEGG   PATHWAY: aml04925
Entry
aml04925                    Pathway                                
Name
Aldosterone synthesis and secretion - Ailuropoda melanoleuca (giant panda)
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
aml04925  Aldosterone synthesis and secretion
aml04925

Other DBs
GO: 0035932
Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100463739  KCNK9; potassium channel subfamily K member 9 [KO:K04919]
100464280  HSD3B1; 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase isoform X1 [KO:K00070] [EC:1.1.1.145 5.3.3.1]
100464578  CACNA1H; voltage-dependent T-type calcium channel subunit alpha-1H [KO:K04855]
100464603  CACNA1G; voltage-dependent T-type calcium channel subunit alpha-1G isoform X1 [KO:K04854]
100464853  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100465232  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100465342  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
100465354  ATP2B1; plasma membrane calcium-transporting ATPase 1 isoform X1 [KO:K05850] [EC:7.2.2.10]
100465395  DAGLB; sn1-specific diacylglycerol lipase beta [KO:K13806] [EC:3.1.1.116]
100465448  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100466224  PRKD3; serine/threonine-protein kinase D3 [KO:K06070] [EC:2.7.11.13]
100466256  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X5 [KO:K04515] [EC:2.7.11.17]
100466965  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100467161  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
100467700  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
100468252  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
100468266  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
100468661  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
100468801  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
100468927  PRKD1; serine/threonine-protein kinase D1 isoform X1 [KO:K06070] [EC:2.7.11.13]
100468967  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
100469080  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
100469231  [KO:K04632]
100469628  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100469689  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
100469861  NPPA; natriuretic peptides A [KO:K12334]
100470137  AGT; angiotensinogen [KO:K09821]
100470257  STAR; steroidogenic acute regulatory protein, mitochondrial [KO:K16931]
100470867  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100470909  CALM2; calmodulin-2 [KO:K02183]
100471164  ADCY3; adenylate cyclase type 3 isoform X2 [KO:K08043] [EC:4.6.1.1]
100471220  AGTR1; type-1 angiotensin II receptor [KO:K04166]
100471375  PRKD2; serine/threonine-protein kinase D2 [KO:K06070] [EC:2.7.11.13]
100471632  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X1 [KO:K08794] [EC:2.7.11.17]
100471747  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100471940  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100472104  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100472122  CALM3; calmodulin-3 [KO:K02183]
100472698  DAGLA; sn1-specific diacylglycerol lipase alpha isoform X1 [KO:K13806] [EC:3.1.1.116]
100472771  NPR1; atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
100472777  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100472835  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
100472949  ATP2B2; plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
100473015  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
100473195  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100473450  LDLR; low-density lipoprotein receptor isoform X2 [KO:K12473]
100473680  [KO:K04632]
100474049  [KO:K00498] [EC:1.14.15.6]
100474121  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100474135  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X2 [KO:K04450]
100474261  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
100474459  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X3 [KO:K04515] [EC:2.7.11.17]
100474779  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100475467  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X2 [KO:K04515] [EC:2.7.11.17]
100476017  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X2 [KO:K09049]
100476284  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100476495  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100476768  ATP2B3; plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
100476922  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
100477326  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100477585  ATP1A3; sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
100477711  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100477778  ORAI1; calcium release-activated calcium channel protein 1 [KO:K16056]
100477852  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
100477888  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100477989  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 isoform X1 [KO:K01539] [EC:7.2.2.13]
100478007  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100478117  [KO:K00513] [EC:1.14.14.16]
100478243  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
100478600  CALML6; calmodulin-like protein 6 [KO:K02183]
100478732  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
100478895  KCNK3; LOW QUALITY PROTEIN: potassium channel subfamily K member 3 [KO:K04914]
100479605  LIPE; hormone-sensitive lipase isoform X1 [KO:K07188] [EC:3.1.1.79]
100479715  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X3 [KO:K04850]
100480274  PDE2A; cGMP-dependent 3',5'-cyclic phosphodiesterase isoform X5 [KO:K18283] [EC:3.1.4.17]
100480351  ATF1; cyclic AMP-dependent transcription factor ATF-1 isoform X1 [KO:K09053]
100480603  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
100480641  [KO:K01539] [EC:7.2.2.13]
100480890  ATP1A4; sodium/potassium-transporting ATPase subunit alpha-4 [KO:K01539] [EC:7.2.2.13]
100481012  ATP1B4; protein ATP1B4 isoform X3 [KO:K01540]
100481177  CALM1; calmodulin-1 [KO:K02183]
100481656  POMC; LOW QUALITY PROTEIN: pro-opiomelanocortin [KO:K05228]
100481755  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100481851  NR4A1; nuclear receptor subfamily 4 group A member 1 [KO:K04465]
100482377  NR4A2; nuclear receptor subfamily 4 group A member 2 isoform X1 [KO:K08558]
100482443  MC2R; adrenocorticotropic hormone receptor [KO:K04200]
100482519  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100483482  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
100484067  SCARB1; scavenger receptor class B member 1 isoform X5 [KO:K13885]
100484519  [KO:K02183]
100484531  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100484596  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
100484719  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
100484762  ATP2B4; plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
100484770  [KO:K02183]
100484838  CACNA1I; LOW QUALITY PROTEIN: voltage-dependent T-type calcium channel subunit alpha-1I [KO:K04856]
117799706  [KO:K02183]
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
aml00140  Steroid hormone biosynthesis
aml00590  Arachidonic acid metabolism
aml04020  Calcium signaling pathway
aml04022  cGMP-PKG signaling pathway
aml04024  cAMP signaling pathway
aml04614  Renin-angiotensin system
aml04960  Aldosterone-regulated sodium reabsorption
KO pathway
ko04925   

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