KEGG   PATHWAY: ko04976Help
Entry
ko04976                     Pathway                                

Name
Bile secretion
Description
Bile is a vital secretion, essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Moreover, bile is an important route of elimination for excess cholesterol and many waste product, bilirubin, drugs and toxic compounds. Bile secretion depends on the function of membrane transport systems in hepatocytes and cholangiocytes and on the structural and functional integrity of the biliary tree. The hepatocytes generate the so-called primary bile in their canaliculi.  Cholangiocytes modify the canalicular bile by secretory and reabsorptive processes as bile passes through the bile ducts. The main solutes in bile are bile acids, which stimulate bile secretion osmotically, as well as facilitate the intestinal absorption of dietary lipids by their detergent properties. Bile acids are also important signalling molecules. Through the activation of nuclear receptors, they regulate their own synthesis and transport rates.
Class
Organismal Systems; Digestive system
BRITE hierarchy
Pathway map
Bile secretion
ko04976

All organismsOrtholog table
Disease
H00208  
Hyperbilirubinemia
H00624  
Familial cholestasis
H00831  
Primary dystonia
H00836  
GLUT1 deficiency syndrome (GLUT1DS)
H00933  
Hereditary pancreatitis
H01016  
Primary bile acid malabsorption
H01213  
Gallbladder disease
H01383  
LDL Receptor Disorder
Other DBs
BSID: 
GO: 
Orthology
K01253  
microsomal epoxide hydrolase [EC:3.3.2.9]
K03460  
solute carrier organic anion transporter family, member 1A
K05043  
solute carrier organic anion transporter family, member 1B
K14341  
solute carrier family 10 (sodium/bile acid cotransporter), member 1
K08204  
MFS transporter, OCT family, solute carrier family 22 (organic anion transporter), member 7
K08205  
MFS transporter, OCT family, solute carrier family 22 (organic anion transporter), member 8
K08198  
MFS transporter, OCT family, solute carrier family 22 (organic cation transporter), member 1
K00021  
hydroxymethylglutaryl-CoA reductase (NADPH) [EC:1.1.1.34]
K13885  
scavenger receptor class B, member 1
K12473  
low-density lipoprotein receptor
K14349  
neutral cholesterol ester hydrolase 1 [EC:3.1.1.-]
K00489  
cholesterol 7alpha-monooxygenase [EC:1.14.13.17]
K08537  
farnesoid X receptor
K08524  
retinoid X receptor alpha
K08563  
nuclear receptor subfamily 0 group B member 2
K11822  
bile-salt sulfotransferase [EC:2.8.2.14]
K08748  
solute carrier family 27 (fatty acid transporter), member 5 [EC:6.2.1.7]
K00659  
bile acid-CoA:amino acid N-acyltransferase [EC:3.1.2.2 2.3.1.65]
K09877  
aquaporin-9
K09869  
aquaporin-8
K05683  
ATP-binding cassette, subfamily G (WHITE), member 5 (sterolin 1)
K05684  
ATP-binding cassette, subfamily G (WHITE), member 8 (sterolin 2)
K05664  
ATP-binding cassette, subfamily B (MDR/TAP), member 11
K05666  
ATP-binding cassette, subfamily C (CFTR/MRP), member 2
K05681  
ATP-binding cassette, subfamily G (WHITE), member 2
K18245  
carbonic anhydrase 2 [EC:4.2.1.1]
K13855  
solute carrier family 4 (anion exchanger), member 2
K05658  
ATP-binding cassette, subfamily B (MDR/TAP), member 1 [EC:3.6.3.44]
K05659  
ATP-binding cassette, subfamily B (MDR/TAP), member 4 [EC:3.6.3.44]
K05742  
solute carrier family 9 (sodium/hydrogen exchanger), member 1
K13857  
solute carrier family 4 (sodium bicarbonate cotransporter), member 5
K05667  
ATP-binding cassette, subfamily C (CFTR/MRP), member 3
K05673  
ATP-binding cassette, subfamily C (CFTR/MRP), member 4
K14360  
organic solute transporter subunit alpha
K14361  
organic solute transporter subunit beta
K04943  
potassium intermediate/small conductance calcium-activated channel subfamily N member 2
K01539  
sodium/potassium-transporting ATPase subunit alpha [EC:3.6.3.9]
K01540  
sodium/potassium-transporting ATPase subunit beta
K01538  
sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K04588  
secretin receptor
K04632  
guanine nucleotide-binding protein G(s) subunit alpha
K08041  
adenylate cyclase 1 [EC:4.6.1.1]
K08042  
adenylate cyclase 2 [EC:4.6.1.1]
K08043  
adenylate cyclase 3 [EC:4.6.1.1]
K08044  
adenylate cyclase 4 [EC:4.6.1.1]
K08045  
adenylate cyclase 5 [EC:4.6.1.1]
K08046  
adenylate cyclase 6 [EC:4.6.1.1]
K08047  
adenylate cyclase 7 [EC:4.6.1.1]
K08048  
adenylate cyclase 8 [EC:4.6.1.1]
K08049  
adenylate cyclase 9 [EC:4.6.1.1]
K04345  
protein kinase A [EC:2.7.11.11]
K05031  
cystic fibrosis transmembrane conductance regulator [EC:3.6.3.49]
K13575  
solute carrier family 4 (sodium bicarbonate cotransporter), member 4
K09866  
aquaporin-4
K09864  
aquaporin-1
K14342  
solute carrier family 10 (sodium/bile acid cotransporter), member 2
K14158  
solute carrier family 5 (sodium/glucose cotransporter), member 1
K12040  
solute carrier family 9 (sodium/hydrogen exchanger), member 3
K07299  
MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1
Compound
C00001  
H2O
C00011  
CO2
C00024  
Acetyl-CoA
C00026  
2-Oxoglutarate
C00031  
D-Glucose
C00051  
Glutathione
C00080  
H+
C00114  
Choline
C00187  
Cholesterol
C00238  
Potassium cation
C00288  
HCO3-
C00315  
Spermidine
C00318  
L-Carnitine
C00366  
Urate
C00486  
Bilirubin
C00504  
Folate
C00575  
3',5'-Cyclic AMP
C00584  
Prostaglandin E2
C00639  
Prostaglandin F2alpha
C00695  
Cholic acid
C00698  
Cl-
C00735  
Cortisol
C00750  
Spermine
C00780  
Serotonin
C00805  
Salicylate
C00865  
Phospholipid
C00942  
3',5'-Cyclic GMP
C01330  
Sodium cation
C01353  
Carbonic acid
C01405  
Aspirin
C01443  
Ouabain
C01576  
Etoposide
C01829  
Thyroxine
C01844  
Pravastatin
C01921  
Glycocholate
C01937  
Methotrexate
C01996  
Acetylcholine
C02165  
Leukotriene B4
C02166  
Leukotriene C4
C02380  
6-Mercaptopurine
C02465  
Triiodothyronine
C02528  
Chenodeoxycholate
C02530  
Cholesterol ester
C02538  
Estrone 3-sulfate
C02918  
1-Methylnicotinamide
C03033  
beta-D-Glucuronoside
C03642  
Taurolithocholate sulfate
C03758  
Dopamine
C03990  
Lithocholic acid
C04483  
Deoxycholic acid
C04555  
Dehydroepiandrosterone sulfate
C05122  
Taurocholate
C05371  
Microcystin LR
C05465  
Taurochenodeoxycholate
C05466  
Glycochenodeoxycholate
C05503  
Estradiol-17beta 3-glucuronide
C05551  
Penicillin G
C05963  
Thromboxane B2
C06526  
Quinine
C06570  
Tetracycline
C06688  
Rifampicin
C06804  
Acetaminophen
C06810  
Acyclovir
C06880  
Cefazolin
C06890  
Ceftizoxime
C06956  
Digoxin
C06999  
Fexofenadine
C07014  
Fluvastatin
C07051  
Indinavir
C07065  
Lamivudine
C07151  
Metformin
C07184  
Valacyclovir
C07185  
Valproic acid
C07201  
Vinblastine
C07207  
Zalcitabine
C07210  
Zidovudine
C07240  
Ritonavir
C07394  
Paclitaxel
C07512  
Tetraethylammonium
C07649  
5-FU
C07660  
Levofloxacin
C07966  
Cerivastatin
C08357  
Estradiol-17beta 3-sulfate
C08439  
Phalloidin
C09955  
Ochratoxin A
C11158  
Topotecan
C11231  
Docetaxel anhydrous
C11245  
Glucuronosyletoposide
C11277  
Adefovir
C11310  
1-Methyl-4-phenylpyridinium
C11363  
Sulfobromophthalein
C11587  
BQ 123
C11754  
Cephaloridine
C12560  
Saquinavir mesylate
C13523  
Secretin
C16114  
Cholecystokinin-8
C16578  
Morphine-6-glucuronide
C16643  
Morphine-3-glucuronide
D00125  
Etoposide (JP16/USP/INN)
D00140  
Erythromycin (JP16/USP/INN)
D00142  
Methotrexate (JP16/USP/INN)
D00184  
Ciclosporin (JP16)
D00186  
Ciprofloxacin (JAN/USP/INN)
D00201  
Tetracycline (JAN/USP/INN)
D00214  
Actinomycin D (JP16)
D00224  
Allopurinol (JP16/USP/INN)
D00240  
Aztreonam (JP16/USP/INN)
D00247  
Bumetanide (JP16/USP/INN)
D00295  
Cimetidine (JP16/USP/INN)
D00298  
Digoxin (JP16/USP)
D00318  
Famotidine (JP16/USP/INN)
D00331  
Furosemide (JP16/USP/INN)
D00333  
Ganciclovir (JAN/USP/INN)
D00340  
Hydrochlorothiazide (JP16/USP/INN)
D00353  
Lamivudine (JAN/USP/INN)
D00359  
Lovastatin (USP/INN)
D00400  
Valsartan (JP16/USAN/INN)
D00422  
Ranitidine (USAN/INN)
D00427  
Ritonavir (JAN/USAN/INN)
D00429  
Saquinavir (JAN/USP/INN)
D00439  
Nitrofurantoin (JAN/USP/INN)
D00453  
Ofloxacin (JP16/USP/INN)
D00456  
Ondansetron (JAN/USP/INN)
D00491  
Paclitaxel (JAN/USP/INN)
D00512  
Phenytoin (JP16/USP/INN)
D00521  
Terfenadine (JAN/USAN/INN)
D00570  
Colchicine (JP16/USP)
D00590  
Sparfloxacin (JAN/USAN/INN)
D00767  
Vecuronium bromide (JAN/USAN/INN)
D00804  
Ivermectin (JAN/USAN/INN)
D01061  
Irinotecan hydrochloride hydrate (JAN)
D01264  
Daunorubicin hydrochloride (JP16/USP)
D01275  
Doxorubicin hydrochloride (JP16/USP)
D01421  
Sodium p-aminophippurate (JAN)
D01745  
Domperidone (JP16/USAN/INN)
D01862  
Pitavastatin calcium (JAN)
D02115  
Methotrexate sodium
D02166  
Mitoxantrone hydrochloride (JAN/USP)
D02214  
Epirubicin hydrochloride (JP16/USAN)
D02216  
Ciprofloxacin hydrochloride (JAN/USP)
D02356  
Verapamil (USAN/INN)
D03130  
Bisantrene hydrochloride (USAN)
D03833  
Indinavir (USAN)
D03899  
Doxorubicin (USAN/INN)
D04931  
Mercaptopurine (INN)
D05246  
Olmesartan (USAN/INN)
D06050  
Technetium Tc 99m tetrofosmin (USP)
D06074  
Tenofovir (USAN)
D07448  
Amitriptyline (INN)
D07538  
Bosentan (INN)
D07626  
Caspofungin (INN)
D07661  
Cerivastatin (INN)
D07776  
Daunorubicin (INN)
D07845  
Diltiazem (INN)
D07866  
Docetaxel (JAN/INN)
D07901  
Epirubicin (INN)
D07907  
Erlotinib (INN)
D07958  
Fexofenadine (INN)
D07986  
Folinic acid (BAN)
D07987  
Folinic acid calcium salt pentahydrate
D08066  
Imatinib (INN)
D08086  
Irinotecan (INN)
D08108  
Lapatinib (INN)
D08144  
Loperamide (INN)
D08146  
Losartan (INN)
D08224  
Mitoxantrone (INN)
D08259  
Nelfinavir (INN)
D08291  
Ofloxacin hydrochloride
D08306  
Oseltamivir (INN)
D08411  
Prazosin (INN)
D08458  
Quinidine (BAN)
D08492  
Rosuvastatin (INN)
D08618  
Topotecan (BAN)
D08675  
Vinblastine (INN)
D08679  
Vincristine (INN)
Reference
  Authors
Meier PJ, Stieger B
  Title
Bile salt transporters.
  Journal
Annu Rev Physiol 64:635-61 (2002)
Reference
  Authors
Kullak-Ublick GA, Beuers U, Paumgartner G
  Title
Hepatobiliary transport.
  Journal
J Hepatol 32:3-18 (2000)
Reference
  Authors
Kosters A, Karpen SJ
  Title
Bile acid transporters in health and disease.
  Journal
Xenobiotica 38:1043-71 (2008)
Reference
  Authors
Anwer MS
  Title
Cellular regulation of hepatic bile acid transport in health and cholestasis.
  Journal
Hepatology 39:581-90 (2004)
Reference
  Authors
Alrefai WA, Gill RK
  Title
Bile acid transporters: structure, function, regulation and pathophysiological implications.
  Journal
Pharm Res 24:1803-23 (2007)
Reference
  Authors
Trauner M, Boyer JL
  Title
Bile salt transporters: molecular characterization, function, and regulation.
  Journal
Physiol Rev 83:633-71 (2003)
Reference
  Authors
Klaassen CD, Aleksunes LM
  Title
Xenobiotic, bile acid, and cholesterol transporters: function and regulation.
  Journal
Pharmacol Rev 62:1-96 (2010)
Reference
  Authors
Trauner M, Wagner M, Fickert P, Zollner G
  Title
Molecular regulation of hepatobiliary transport systems: clinical implications for understanding and treating cholestasis.
  Journal
J Clin Gastroenterol 39:S111-24 (2005)
Reference
  Authors
  Title
  Journal
Reference
  Authors
Esteller A
  Title
Physiology of bile secretion.
  Journal
World J Gastroenterol 14:5641-9 (2008)
Reference
  Authors
Takikawa H
  Title
Hepatobiliary transport of bile acids and organic anions.
  Journal
J Hepatobiliary Pancreat Surg 9:443-7 (2002)
Reference
  Authors
St-Pierre MV, Kullak-Ublick GA, Hagenbuch B, Meier PJ
  Title
Transport of bile acids in hepatic and non-hepatic tissues.
  Journal
J Exp Biol 204:1673-86 (2001)
Reference
  Authors
Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K
  Title
Targeting bile-acid signalling for metabolic diseases.
  Journal
Nat Rev Drug Discov 7:678-93 (2008)
Reference
  Authors
Pauli-Magnus C, Stieger B, Meier Y, Kullak-Ublick GA, Meier PJ
  Title
Enterohepatic transport of bile salts and genetics of cholestasis.
  Journal
J Hepatol 43:342-57 (2005)
Reference
  Authors
Pellicoro A, Faber KN
  Title
Review article: The function and regulation of proteins involved in bile salt biosynthesis and transport.
  Journal
Aliment Pharmacol Ther 26 Suppl 2:149-60 (2007)
Reference
  Authors
Jonker JW, Stedman CA, Liddle C, Downes M
  Title
Hepatobiliary ABC transporters: physiology, regulation and implications for disease.
  Journal
Front Biosci 14:4904-20 (2009)
Reference
  Authors
Modica S, Bellafante E, Moschetta A
  Title
Master regulation of bile acid and xenobiotic metabolism via the FXR, PXR and CAR trio.
  Journal
Front Biosci 14:4719-45 (2009)
Reference
  Authors
Cai SY, Boyer JL
  Title
FXR: a target for cholestatic syndromes?
  Journal
Expert Opin Ther Targets 10:409-21 (2006)
Reference
  Authors
Ballatori N, Li N, Fang F, Boyer JL, Christian WV, Hammond CL
  Title
OST alpha-OST beta: a key membrane transporter of bile acids and conjugated steroids.
  Journal
Front Biosci 14:2829-44 (2009)
Reference
  Authors
Roma MG, Crocenzi FA, Sanchez Pozzi EA
  Title
Hepatocellular transport in acquired cholestasis: new insights into functional, regulatory and therapeutic aspects.
  Journal
Clin Sci (Lond) 114:567-88 (2008)
Reference
  Authors
Arrese M, Macias RI, Briz O, Perez MJ, Marin JJ
  Title
Molecular pathogenesis of intrahepatic cholestasis of pregnancy.
  Journal
Expert Rev Mol Med 10:e9 (2008)

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