Cholestasis (Homo sapiens)

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10947319562152011818221316211121714Hepatocyte(BA uptake)CationsSystemic circulationCholesterolNa+BaRegulation of BA synthesis and transportPPAR-aPhospholipidsNR1I3ABCG8ABCG5ABCB11Bile canaliculusNR1H4Tight junctionHDLCholesteryl estersABCC2Acetyl CoAmEHLDLOATPsHCO3(-)HMGCRTJP2GSHBile acidABCB4RXRAATP8B1NTCPOCT1MRP3MRP4LDLRSR-B1NR1H4Bile acidRXRATJP2HepatocyteABCB11ABCB4Tight junctionBaBaBaNa+Na+BaBaGSHHCO3(-)BaBaBaBaBa(Biliary secretion - normal state)(Alternative BA export)PhospholipidsCholStimulationTranslocationTranscription - TranslationCatalysisInhibitionPathway regulation


Description

Genetic causes of cholestasis

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Quality Tags

Ontology Terms

 

Bibliography

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  1. Kassam A, Miao B, Young PR, Mukherjee R; ''Retinoid X receptor (RXR) agonist-induced antagonism of farnesoid X receptor (FXR) activity due to absence of coactivator recruitment and decreased DNA binding.''; J Biol Chem, 2003 PubMed Europe PMC Scholia
  2. Pineda Torra I, Claudel T, Duval C, Kosykh V, Fruchart JC, Staels B; ''Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor.''; Mol Endocrinol, 2003 PubMed Europe PMC Scholia
  3. Yu L, Gupta S, Xu F, Liverman AD, Moschetta A, Mangelsdorf DJ, Repa JJ, Hobbs HH, Cohen JC; ''Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion.''; J Biol Chem, 2005 PubMed Europe PMC Scholia
  4. Renga B, Migliorati M, Mencarelli A, Cipriani S, D'Amore C, Distrutti E, Fiorucci S; ''Farnesoid X receptor suppresses constitutive androstane receptor activity at the multidrug resistance protein-4promoter.''; Biochim Biophys Acta, 2011 PubMed Europe PMC Scholia
  5. Fiorucci S, Zampella A, Distrutti E; ''Development of FXR, PXR and CAR agonists and antagonists for treatment of liver disorders.''; Curr Top Med Chem, 2012 PubMed Europe PMC Scholia
  6. Gautherot J, Claudel T, Cuperus F, Fuchs CD, Falguières T, Trauner M; ''Thyroid hormone receptor β1 stimulatesABCB4to increase biliary phosphatidylcholine excretion in mice.''; J Lipid Res, 2018 PubMed Europe PMC Scholia
  7. Friesen JA, Rodwell VW; ''The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases.''; Genome Biol, 2004 PubMed Europe PMC Scholia
  8. Chiang JY; ''Bile acid metabolism and signaling.''; Compr Physiol, 2013 PubMed Europe PMC Scholia
  9. Chang TY, Chang CC, Ohgami N, Yamauchi Y; ''Cholesterol sensing, trafficking, and esterification.''; Annu Rev Cell Dev Biol, 2006 PubMed Europe PMC Scholia
  10. More VR, Campos CR, Evans RA, Oliver KD, Chan GN, Miller DS, Cannon RE; ''PPAR-α, a lipid-sensing transcription factor, regulates blood-brain barrier efflux transporter expression.''; J Cereb Blood Flow Metab, 2017 PubMed Europe PMC Scholia
  11. Zollner G, Fickert P, Fuchsbichler A, Silbert D, Wagner M, Arbeiter S, Gonzalez FJ, Marschall HU, Zatloukal K, Denk H, Trauner M; ''Role of nuclear bile acid receptor, FXR, in adaptive ABC transporter regulation by cholic and ursodeoxycholic acid in mouse liver, kidney and intestine.''; J Hepatol, 2003 PubMed Europe PMC Scholia
  12. Eloranta JJ, Kullak-Ublick GA; ''The role of FXR in disorders of bile acid homeostasis.''; Physiology (Bethesda), 2008 PubMed Europe PMC Scholia
  13. Chang TY, Li BL, Chang CC, Urano Y; ''Acyl-coenzyme A:cholesterol acyltransferases.''; Am J Physiol Endocrinol Metab, 2009 PubMed Europe PMC Scholia
  14. Ding L, Yang L, Wang Z, Huang W; ''Bile acid nuclear receptor FXR and digestive system diseases.''; Acta Pharm Sin B, 2015 PubMed Europe PMC Scholia
  15. Ghonem NS, Ananthanarayanan M, Soroka CJ, Boyer JL; ''Peroxisome proliferator-activated receptor α activates human multidrug resistance transporter 3/ATP-binding cassette protein subfamily B4 transcription and increases rat biliary phosphatidylcholine secretion.''; Hepatology, 2014 PubMed Europe PMC Scholia
  16. Kim I, Ahn SH, Inagaki T, Choi M, Ito S, Guo GL, Kliewer SA, Gonzalez FJ; ''Differential regulation of bile acid homeostasis by the farnesoid X receptor in liverand intestine.''; J Lipid Res, 2007 PubMed Europe PMC Scholia
  17. Hiebl V, Ladurner A, Latkolik S, Dirsch VM; ''Natural products as modulators of the nuclear receptors and metabolic sensors LXR, FXR and RXR.''; Biotechnol Adv, 2018 PubMed Europe PMC Scholia
  18. Dong B, Singh AB, Guo GL, Young M, Liu J; ''Activation of FXR by obeticholic acid induces hepatic gene expression of SR-BI through a novel mechanism of transcriptional synergy with the nuclear receptor LXR.''; Int J Mol Med, 2019 PubMed Europe PMC Scholia
  19. Koh S, Takada T, Kukuu I, Suzuki H; ''FIC1-mediated stimulation of FXR activity is decreased with PFIC1 mutations in HepG2 cells.''; J Gastroenterol, 2009 PubMed Europe PMC Scholia
  20. Moffit JS, Aleksunes LM, Maher JM, Scheffer GL, Klaassen CD, Manautou JE; ''Induction of hepatic transporters multidrug resistance-associated proteins (Mrp) 3 and 4 by clofibrate is regulated by peroxisome proliferator-activated receptor alpha.''; J Pharmacol Exp Ther, 2006 PubMed Europe PMC Scholia
  21. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM, Edwards PA; ''Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor.''; J Biol Chem, 2002 PubMed Europe PMC Scholia
  22. Huang L, Zhao A, Lew JL, Zhang T, Hrywna Y, Thompson JR, de Pedro N, Royo I, Blevins RA, Peláez F, Wright SD, Cui J; ''Farnesoid X receptor activates transcription of the phospholipid pump MDR3.''; J Biol Chem, 2003 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134499view06:35, 22 July 2024EgonwRemoved template comments
134386view19:15, 21 July 2024EweitzRemove template comments
127769view13:15, 3 December 2023EgonwChEBI id for Na+ instead of the "Na" atom
123341view06:46, 17 July 2022EgonwCholesterol typed as Metabolite
123074view10:24, 24 June 2022FehrhartOntology Term : 'hepatocyte' added !
123057view08:20, 22 June 2022VPenchevaChange to legend, now complete
122906view12:35, 31 May 2022SusanOntology Term : 'cholestasis pathway' added !
122905view12:34, 31 May 2022SusanOntology Term : 'cholestasis' added !
122884view14:29, 28 May 2022VPenchevaNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ABCB11ProteinO95342 (Uniprot-TrEMBL) Bile salt export pump
ABCB4ProteinP21439 (Uniprot-TrEMBL) Multidrug resistance protein 3
ABCC2ProteinQ92887 (Uniprot-TrEMBL) Multidrug resistance-associated protein 2
ABCG5ProteinQ9H222 (Uniprot-TrEMBL)
ABCG8ProteinQ9H221 (Uniprot-TrEMBL)
ATP8B1ProteinO43520 (Uniprot-TrEMBL) familial intrahepatic cholestasis 1
Acetyl CoAMetabolite15351 (ChEBI)
BaMetaboliteCHEBI:22868 (ChEBI)
Bile acidMetabolite3098 (ChEBI)
Bile canaliculus
CationsMetaboliteCHEBI:25697 (ChEBI)
CholMetaboliteCHEBI:16113 (ChEBI)
CholesterolMetaboliteCHEBI:16113 (ChEBI)
Cholesteryl estersMetaboliteCHEBI:17002 (ChEBI)
GSHMetaboliteCHEBI:16856 (ChEBI)
HCO3(-)MetaboliteCHEBI:17544 (ChEBI)
HDLMetaboliteCHEBI:39025 (ChEBI)
HMGCRGeneProductP04035 (Uniprot-TrEMBL)
LDLMetaboliteCHEBI:39026 (ChEBI)
LDLRProteinP01130 (Uniprot-TrEMBL) microsomal epoxide hydrolase
MRP3ProteinO15438 (Uniprot-TrEMBL) Multidrug resistance associated protein 3
MRP4ProteinO15439 (Uniprot-TrEMBL) Multidrug resistance associated protein 4
NR1H4ProteinQ96RI1 (Uniprot-TrEMBL) Farnesoid X Receptor
NR1I3GeneProductENSG00000143257 (Ensembl)
NTCPProteinQ14973 (Uniprot-TrEMBL) sodium/bile acid cotransporter
Na+MetaboliteCHEBI:29101 (ChEBI)
OATPsProteinP46721 (Uniprot-TrEMBL) Solute carrier organic anion transporter family member
OCT1ProteinO15245 (Uniprot-TrEMBL) Organic cation transporter 1
PPAR-aMetaboliteCHEBI:70782 (ChEBI)
PhospholipidsMetaboliteCHEBI:16247 (ChEBI)
RXRAProteinP19793 (Uniprot-TrEMBL) Retinoid X receptor
Regulation of BA synthesis and transportPathwayWP5176 (WikiPathways)
SR-B1ProteinQ8WTV0 (Uniprot-TrEMBL) Scavenger receptor class B member 1
TJP2ProteinQ9UDY2 (Uniprot-TrEMBL) Tight junction protein ZO-2
Tight junctionComplexQ1053832 (Wikidata)
mEHProteinP07099 (Uniprot-TrEMBL) microsomal epoxide hydrolase

Annotated Interactions

No annotated interactions

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