Disorders of bile acid synthesis and biliary transport (WP5176)

Homo sapiens

This pathway model displays disorders of bile acid synthesis and biliary transport. Bile acids have a crucial role in the absorption of lipids and hydrophilic vitamins. Furthermore, bile acids aid in the maintenance of cholesterol homeostasis, excretion of toxic substances, processing of food intake, and used as signaling molecules influencing glucose homeostasis, lipid metabolism, and energy expenditure. First, bile acids with a low solubility (less hydrophilic, unconjugated) must be activated using CoA, so that conjugation to taurine or glycine can happen. This model includes 20 disorders, of which 14 are enzyme deficiencies, and 6 are related to transporters. The enzyme deficiencies include 3β-Dehydrogenase deficiency, 5β-Reductase deficiency, Spastic Paraplegia 5A, Cholesterol 7α-hydroxylase deficiency, Sterol 27-hydroxylase deficiency, α-Methylacyl-CoA racemase (AMACR) deficiency, Bile acid amidation defect, and Bile acid-CoA ligase deficiency (BA CoA LD, BACS), congenital bile acid synthesis defect 6 and type 5, D-bifunctional protein deficiency, sterol carrier protein 2 deficiency. Disorders of transporters are related to deficiencies in ATP8B1 (Progressive familial intrahepatic cholestasis type 1; PFIC1), ABCB11 (Progressive familial intrahepatic cholestasis type 2; PFIC 2), ABCB4 (Progressive familial intrahepatic cholestasis type 3), and ABCC2 (Dubin-Johnson syndrome), as well as Rotor Syndrome (linked to two distinct genes, OATP1B1 and OATP1B3, related to taurocholate and glycocholate transport). This pathway is based on Chapter 34 of Blau’s ‘Physicians Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases (ISBN 3642403360 (978-3642403361)), edition 4 (and is currently in the process of being updated to edition 5, Chapter 56). We would like to thank two authors from this chapter (Frédéric M. Vaz and Sacha Ferdinandusse) for their efforts in curating this pathway model!


Maria van de Meent , Eric Weitz , Denise Slenter , and Egon Willighagen


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Homo sapiens


Inherited Metabolic Disorders (IMD) Pathways Rare Diseases


Disease Ontology

progressive familial intrahepatic cholestasis 3 progressive familial intrahepatic cholestasis 2 progressive familial intrahepatic cholestasis 1 cerebrotendinous xanthomatosis congenital bile acid synthesis defect hereditary spastic paraplegia 5A alpha-methylacyl-CoA racemase deficiency Dubin-Johnson syndrome

Pathway Ontology

disease pathway inborn error of metabolism pathway bile acid transport pathway transport pathway bile acid biosynthetic pathway primary bile acid biosynthetic pathway secondary bile acid biosynthetic pathway

Cell Type Ontology



Label Type Compact URI Comment
3alpha,7alpha,12alpha-Trihydroxy-5beta-cholest-24-enoyl-CoA Metabolite chebi:27505
(24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy-5beta-cholestan-26-oyl-CoA Metabolite chebi:52050
3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid Metabolite chebi:16577
3alpha,7alpha,24-trihydroxy-5beta-cholestan-26-oyl-CoA Metabolite wikidata:Q27103111
3alpha,7alpha-Dihydroxy-5beta-cholest-24-enoyl-CoA Metabolite chebi:27393
glycocholate Metabolite chebi:29746
taurocholate Metabolite chebi:36257 AKA cholyltaurine
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oic acid Metabolite chebi:18402 AKA THCA, trihydroxycholestanoic acid, 3α,7α,12α-trihydroxy-5β-cholestanoic acid
3alpha,7alpha-dihydroxy-24-oxo-5beta-cholestan-26-oyl-CoA Metabolite chebi:87704
Taurine Metabolite chebi:507393
3α,7α,12α-trihydroxy-24-oxo-5β-cholestan-26-oyl-CoA Metabolite chebi:27379
(25S)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA Metabolite chebi:37643
5beta-cholestane-3alpha,7alpha,26-triol Metabolite chebi:28540
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al Metabolite chebi:16466
3alpha,7alpha-dihydroxy-5beta-cholestan-26-al Metabolite chebi:27428
5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol Metabolite chebi:17278
7alpha,26-dihydroxycholest-4-en-3-one Metabolite chebi:48825
7alpha,26-dihydroxy-5beta-cholestan-3-one Metabolite chebi:48778
Phosphatidylserine Metabolite chebi:18303
3beta-Hydroxy-5-cholestenoic acid Metabolite chebi:81014
Bile acid Metabolite chebi:36277
phosphatidylcholines Metabolite chebi:49183
Bilirubin glucuronide Metabolite chebi:16427
chenodeoxycholate(1-) Metabolite chebi:36234
cholesterol Metabolite chebi:16113
7-alpha-Hydroxycholesterol Metabolite chebi:17500
7alpha,12alpha-Dihydroxy-4-cholesten-3-one Metabolite chebi:28477
(25S)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoA Metabolite hmdb:HMDB0060306
5beta-cholestane-3alpha,7alpha,12alpha-triol Metabolite chebi:16496
Glycocholic acid Metabolite chebi:17687
(25R)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoA Metabolite hmdb:HMDB0060304
cholyl-CoA Metabolite chebi:15519
3beta,7alpha-Dihydroxy-5-cholestenoate Metabolite hmdb:HMDB0012454 Alternative name: 3β,7α-Dihydroxy-5-cholestenoic acid
Taurocholic acid Metabolite chebi:36257
Chenodeoxycholoyl-CoA Metabolite chebi:28701
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one Metabolite chebi:2288
5beta-cholestane-3alpha,7alpha-diol Metabolite chebi:28047
cholate Metabolite chebi:29747
27-Hydroxycholesterol Metabolite chebi:17703 C27-carboxylic acid
7alpha-hydroxy-5beta-cholestan-3-one Metabolite chebi:2290
7alpha-Hydroxy-4-cholesten-3-one Metabolite chebi:17899
Glycochenodeoxycholic acid Metabolite chebi:36274
Taurochenodeoxycholic acid Metabolite chebi:16525
5beta-Cholestane-3alpha,7alpha,27-triol Metabolite hmdb:HMDB0060138 Alternative name: 5β-Cholestan-3α,7α,27-triol
Bilirubin glucuronide Metabolite chebi:16427
phosphatidylcholines Metabolite chebi:49183
Phosphatidylserine Metabolite chebi:18303
Bile acid Metabolite chebi:36277
cholesterol Metabolite chebi:16113
glycocholate Metabolite chebi:29746
taurocholate Metabolite chebi:36257 AKA cholyltaurine
(25R)-3alpha,7alpha-Dihydroxy-5beta-cholestanoyl-CoA Metabolite hmdb:HMDB0060304
(25R)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestan-26-oyl-CoA Metabolite chebi:37642 AKA THC-CoA
(25R)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestan-26-oyl-CoA Metabolite chebi:37642 AKA THC-CoA
SLCO1B1 GeneProduct uniprot:Q9Y6L6
SLCO1B3 GeneProduct uniprot:Q9NPD5
ACOX2 GeneProduct ensembl:ENSG00000168306
SCPx GeneProduct uniprot:P22307 Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoA [Source: UniProt]
ABCB11 GeneProduct ensembl:ENSG00000073734
ABCC2 GeneProduct ensembl:ENSG00000023839
SLC27A5 GeneProduct ensembl:ENSG00000083807
CYP7A1 GeneProduct ensembl:ENSG00000167910 aka sterol 7α-hydroxylase
ABCB4 GeneProduct ensembl:ENSG00000005471
CYP7B1 GeneProduct ensembl:ENSG00000172817
HSD3B7 GeneProduct ensembl:ENSG00000099377
AKR1D1 GeneProduct ensembl:ENSG00000122787
CYP8B1 GeneProduct uniprot:Q9UNU6
AMACR GeneProduct uniprot:Q9UHK6
HSD3B7 GeneProduct ensembl:ENSG00000099377
ATP8B1 GeneProduct ensembl:ENSG00000081923
CYP27A1 GeneProduct ensembl:ENSG00000135929 AKA sterol 27-hydroxylase
AKR1D1 GeneProduct ensembl:ENSG00000122787
CYP27A1 GeneProduct ensembl:ENSG00000135929
HSD17B4 GeneProduct ensembl:ENSG00000133835
CYP27A1 GeneProduct ensembl:ENSG00000135929
BACS Protein uniprot:Q9Y2P5 AKA Bile acid-CoA ligase, gene symbol: SLC27A5, Long-chain fatty acid transport protein 5
CBH Protein uniprot:P54965 AKA conjugated bile acid hydrolase, or CBAH, bacterial conversion
Tentatively annotated for species Clostridium perfringens (strain 13 / Type A), C. perfringens, based on Table 1 from PMID: 30098054
Aldo-keto reductase family 1 member C4 Protein uniprot:P17516
Aldo-keto reductase family 1 member C4 Protein uniprot:P17516
Very long-chain acyl-CoA synthetase Protein uniprot:O14975 Full name: very long chain acyl-CoA synthase (VLCS)/di-/trihydroxycholestanoic acid-CoA ligase
Check annotation of this enzyme!
ABCD3 or PMP70 Protein uniprot:P28288
Bile acid-CoA:amino acid N-acyltransferase Protein uniprot:Q14032 amino acid N-acyltransferase (BAAT), which has a dual localization (peroxisome and cytosol)
Bile acid-CoA:amino acid N-acyltransferase Protein uniprot:Q14032 amino acid N-acyltransferase (BAAT), which has a dual localization (peroxisome and cytosol)
NTCP Protein uniprot:Q14973 AKA SLC10A1
OATP1B1 Protein uniprot:Q9Y6L6 AKA SLCO1B1
OATP1B3 Protein uniprot:Q9NPD5 AKA SLCO1B3
MRP2 Protein uniprot:Q92887 AKA ABCC2
MRP3 Protein uniprot:O15438 AKA ABCC3
BSEP Protein uniprot:O95342 AKA ABCB11
MRP4 Protein uniprot:O15439 AKA ABBC4 (PMID:21103970); according to UniProt ABCC4 is the correct gene name.
OSTα Protein uniprot:Q86UW1 heteromeric transporter OSTα-OSTβ , assumed to be gene SLC51A based on UniProt entry (gene name not mentioned in publication)
OSTβ Protein uniprot:Q86UW2 heteromeric transporter OSTα-OSTβ , assumed to be gene SLC51B based on UniProt entry (gene name not mentioned in publication)
MDR1 Protein uniprot:P08183 AKA ABCB1A (PMID:21103970), UniProt: ABCB1 (ABCB1A is used for mouse). MDR1A in Figure (PMID:21103970)
ILBP Protein uniprot:P51161 AKA FABP6
ASBT Protein uniprot:Q12908 AKA SLC10A2


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