Bile acid synthesis and enterohepatic circulation (WP4389)

Homo sapiens

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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 [https://www.ncbi.nlm.nih.gov/pubmed/29653253 Wang et al].

Authors

Viole H , Denise Slenter , Egon Willighagen , Kristina Hanspers , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

enterocyte hepatocyte

Pathway Ontology

bile acid biosynthetic pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
Bile Acid Metabolite chebi:3098
Bile acid Metabolite chebi:3098
Cholesterol Metabolite chebi:16113
LDL cholesterol Metabolite chebi:47774
MAPK1 GeneProduct ensembl:ENSG00000100030
FXR1 GeneProduct ensembl:ENSG00000114416
ABCG8 GeneProduct ensembl:ENSG00000143921
LDLR GeneProduct ensembl:ENSG00000130164
CYP7A1 GeneProduct ensembl:ENSG00000167910
ABCB11 GeneProduct ensembl:ENSG00000073734
ABCG5 GeneProduct ensembl:ENSG00000138075
MAPK3 GeneProduct ensembl:ENSG00000102882
FGF19 GeneProduct ensembl:ENSG00000162344
LDL Protein chebi:39026
NTCP Protein uniprot:Q14973
FGFR4 Protein uniprot:P22455
ASBT Protein uniprot:Q12908 '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]

References

  1. Cholesterol and bile acid-mediated regulation of autophagy in fatty liver diseases and atherosclerosis. Wang Y, Ding WX, Li T. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Jul;1863(7):726–33. PubMed Europe PMC Scholia