Bile acid synthesis and enterohepatic circulation (Homo sapiens)

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Hepatocyte1EnterocyteCYP7A1NTCPBile acidABCB11ABCG8MAPK1LDLRLDLFGFR4ABCG5Bile AcidASBTBile AcidCholesterolDe Novo SynthesisFXR1FXR1LDL cholesterolMAPK3FGF19


Description

Bile Acid Synthesis and Enterohepathic Circulation.

In hepatocytes, cholesterol is acquired through de novo synthesis as well as receptor-mediated endocytosis of cholesterol-rich lipoproteins. Cholesterol is eliminated through bile acid synthesis and secretion. The first (and rate-limiting) step in cholesterol conversion to bile acids is catalyzed by CYP7A1. Bile acids are then secreted into the bile via ABCB11 and released into the small intestine. The majority of bile acids are re-absorbed into the enterocytes via ASBT and transported back to the liver via portal circulation via NTCP. In the hepatocyte, bile acids activate FXR, which inhibits CYP7A1. In the small intestine, bile acids also activate FXR to induce FGF15, which subsequently binds and activates FGFR4, leading to inhibition of CYP7A1, partially via ERK signaling. Based on figure 1 in Wang et al.

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Bibliography

  1. Wang Y, Ding WX, Li T; ''Cholesterol and bile acid-mediated regulation of autophagy in fatty liver diseases and atherosclerosis.''; Biochim Biophys Acta Mol Cell Biol Lipids, 2018 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
129532view01:27, 9 May 2024EweitzModified title
129531view01:25, 9 May 2024EweitzOntology Term : '' added !
129530view01:25, 9 May 2024EweitzOntology Term : '' added !
123503view04:59, 29 July 2022EgonwMade a pathway clickable
116629view11:16, 9 May 2021EweitzModified title
103474view09:17, 6 March 2019DeSlLayout update
103473view09:16, 6 March 2019DeSlUpdating lit ref (again)
103472view09:14, 6 March 2019DeSlUpdated lit. ref.
103471view09:14, 6 March 2019DeSlAdded more IDs.
103417view23:27, 27 February 2019KhanspersModified description
103416view23:20, 27 February 2019KhanspersModified description
103415view23:17, 27 February 2019Khanspersfinalizing
101972view14:04, 21 November 2018DeSlChanged secondary to primary ChEBI ID for serotonin.
98957view05:24, 18 October 2018EgonwAdded an ChEBI id for bile acid (=compound class).
98909view15:29, 15 October 2018DeSlAdded lit. ref again, hope all info is now on WPs
98908view15:28, 15 October 2018DeSlConnected info from lit ref according to description of figure
98855view23:07, 9 October 2018VioletHOntology Term : 'bile acid biosynthetic pathway' added !
98854view23:06, 9 October 2018VioletHNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ABCB11GeneProductENSG00000073734 (Ensembl)
ABCG5GeneProductENSG00000138075 (Ensembl)
ABCG8GeneProductENSG00000143921 (Ensembl)
ASBT ProteinQ12908 (Uniprot-TrEMBL) "The SLC10A2 (solute carrier family 10 member 2) gene in humans encodes the bile acid:sodium symporter known as the apical sodium–bile acid transporter (ASBT) or as the ileal bile acid transporter (IBAT)." [https://en.wikipedia.org/wiki/SLC10A2]
Bile AcidMetaboliteCHEBI:3098 (ChEBI)
Bile acidMetaboliteCHEBI:3098 (ChEBI)
CYP7A1GeneProductENSG00000167910 (Ensembl)
CholesterolMetaboliteCHEBI:16113 (ChEBI)
De Novo Synthesis PathwayWP197 (WikiPathways)
FGF19GeneProductENSG00000162344 (Ensembl)
FGFR4ProteinP22455 (Uniprot-TrEMBL)
FXR1GeneProductENSG00000114416 (Ensembl)
LDL cholesterolMetaboliteCHEBI:47774 (ChEBI)
LDLProteinCHEBI:39026 (ChEBI)
LDLRGeneProductENSG00000130164 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
NTCPProteinQ14973 (Uniprot-TrEMBL)

Annotated Interactions

No annotated interactions

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