Bile acid synthesis and enterohepatic circulation (Homo sapiens)
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Description
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.
Quality Tags
Ontology Terms
Bibliography
- 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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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
ABCB11 | GeneProduct | ENSG00000073734 (Ensembl) | |
ABCG5 | GeneProduct | ENSG00000138075 (Ensembl) | |
ABCG8 | GeneProduct | ENSG00000143921 (Ensembl) | |
ASBT | Protein | Q12908 (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 Acid | Metabolite | CHEBI:3098 (ChEBI) | |
Bile acid | Metabolite | CHEBI:3098 (ChEBI) | |
CYP7A1 | GeneProduct | ENSG00000167910 (Ensembl) | |
Cholesterol | Metabolite | CHEBI:16113 (ChEBI) | |
De Novo Synthesis | Pathway | WP197 (WikiPathways) | |
FGF19 | GeneProduct | ENSG00000162344 (Ensembl) | |
FGFR4 | Protein | P22455 (Uniprot-TrEMBL) | |
FXR1 | GeneProduct | ENSG00000114416 (Ensembl) | |
LDL cholesterol | Metabolite | CHEBI:47774 (ChEBI) | |
LDL | Protein | CHEBI:39026 (ChEBI) | |
LDLR | GeneProduct | ENSG00000130164 (Ensembl) | |
MAPK1 | GeneProduct | ENSG00000100030 (Ensembl) | |
MAPK3 | GeneProduct | ENSG00000102882 (Ensembl) | |
NTCP | Protein | Q14973 (Uniprot-TrEMBL) |
Annotated Interactions
No annotated interactions