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Record Information
Version3.6
Creation Date2006-08-13 06:26:12 UTC
Update Date2016-02-11 01:06:27 UTC
HMDB IDHMDB03873
Secondary Accession NumbersNone
Metabolite Identification
Common Name3a,7a,12a-Trihydroxy-5b-cholestanoic acid
Description3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestanoic acid is a bile acid. Bile acids are steroid acids found predominantly in bile of mammals. The distinction between different bile acids is minute, depends only on presence or absence of hydroxyl groups on positions 3, 7, and 12. Bile acids are physiological detergents that facilitate excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphipathic molecules derived from the catabolism of cholesterol. They modulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and have been implicated in the regulation of all the key enzymes involved in cholesterol homeostasis. Bile acids recirculate through the liver, bile ducts, small intestine and portal vein to form an enterohepatic circuit. They exist as anions at physiological pH and, consequently, require a carrier for transport across the membranes of the enterohepatic tissues. The unique detergent properties of bile acids are essential for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids have potent toxic properties (e.g., membrane disruption) and there are a plethora of mechanisms to limit their accumulation in blood and tissues.
Structure
Thumb
Synonyms
ValueSource
(3alpha,5beta,7alpha,12alpha,25R)-3,7,12-Trihydroxycholestan-26-Oic acidChEBI
(3a,5b,7a,12a,25R)-3,7,12-Trihydroxycholestan-26-OateGenerator
(3a,5b,7a,12a,25R)-3,7,12-Trihydroxycholestan-26-Oic acidGenerator
(3alpha,5beta,7alpha,12alpha,25R)-3,7,12-Trihydroxycholestan-26-OateGenerator
(3α,5β,7α,12α,25R)-3,7,12-trihydroxycholestan-26-OateGenerator
(3α,5β,7α,12α,25R)-3,7,12-trihydroxycholestan-26-Oic acidGenerator
(25R)-3a,7a,12a-Trihydroxy-5b-cholestan-26-OateGenerator
(25R)-3a,7a,12a-Trihydroxy-5b-cholestan-26-Oic acidGenerator
(25R)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestan-26-OateGenerator
(25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-OateGenerator
(25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-Oic acidGenerator
(25R)-3-alpha,7-alpha,12-alpha-Trihydroxy-5-beta-cholestan-26-OateHMDB
(25R)-3-alpha,7-alpha,12-alpha-Trihydroxy-5-beta-cholestan-26-Oic acidHMDB
3-alpha,7-alpha,12-alpha-Trihydroxy-5-beta-cholestanateHMDB
3a,7a,12a-Trihydroxy-5b-cholestanoateHMDB
3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestanoateHMDB
3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestanoic acidHMDB
Chemical FormulaC27H46O5
Average Molecular Weight450.6511
Monoisotopic Molecular Weight450.334524582
IUPAC Name(2R,6R)-2-methyl-6-[(1S,2S,5R,7S,9R,10R,11S,14R,15R,16S)-5,9,16-trihydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]heptanoic acid
Traditional Name(2R,6R)-2-methyl-6-[(1S,2S,5R,7S,9R,10R,11S,14R,15R,16S)-5,9,16-trihydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-14-yl]heptanoic acid
CAS Registry Number33964-75-9
SMILES
[H][C@@]12CC[C@H]([C@H](C)CCC[C@@H](C)C(O)=O)[C@@]1(C)[C@@H](O)C[C@@]1([H])[C@@]2([H])[C@H](O)C[C@]2([H])C[C@H](O)CC[C@]12C
InChI Identifier
InChI=1S/C27H46O5/c1-15(6-5-7-16(2)25(31)32)19-8-9-20-24-21(14-23(30)27(19,20)4)26(3)11-10-18(28)12-17(26)13-22(24)29/h15-24,28-30H,5-14H2,1-4H3,(H,31,32)/t15-,16-,17+,18-,19-,20+,21+,22-,23+,24+,26+,27-/m1/s1
InChI KeyInChIKey=CNWPIIOQKZNXBB-WBYPBBSPSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as trihydroxy bile acids, alcohols and derivatives. These are prenol lipids structurally characterized by a bile acid or alcohol which bears three hydroxyl groups.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassBile acids, alcohols and derivatives
Direct ParentTrihydroxy bile acids, alcohols and derivatives
Alternative Parents
Substituents
  • Trihydroxy bile acid, alcohol, or derivatives
  • Steroid acid
  • 7-hydroxysteroid
  • 3-alpha-hydroxysteroid
  • Hydroxysteroid
  • 12-hydroxysteroid
  • 3-hydroxysteroid
  • Medium-chain fatty acid
  • Fatty acyl
  • Fatty acid
  • Cyclic alcohol
  • Secondary alcohol
  • Polyol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
  • 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oic acid (CHEBI:48043 )
  • C27 bile acids, alcohols, and derivatives (LMST04030151 )
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Food
Biofunction
  • Cell signaling
  • Fat solubilization and Waste products
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.022 mg/mLALOGPS
logP3.12ALOGPS
logP3.91ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)4.62ChemAxon
pKa (Strongest Basic)-0.16ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area97.99 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity124.57 m3·mol-1ChemAxon
Polarizability53.21 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Extracellular
Biofluid Locations
  • Blood
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
27-Hydroxylase DeficiencySMP00720Not Available
Bile Acid BiosynthesisSMP00035map00120
Cerebrotendinous Xanthomatosis (CTX)SMP00315Not Available
Congenital Bile Acid Synthesis Defect Type IISMP00314Not Available
Congenital Bile Acid Synthesis Defect Type IIISMP00318Not Available
Familial Hypercholanemia (FHCA)SMP00317Not Available
Zellweger SyndromeSMP00316Not Available
Normal Concentrations
Not Available
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.76 uMAdult (>18 years old)BothInfantile Refsum disease details
Associated Disorders and Diseases
Disease References
Refsum's disease
  1. Poll-The BT, Saudubray JM, Ogier H, Schutgens RB, Wanders RJ, Schrakamp G, van den Bosch H, Trijbels JM, Poulos A, Moser HW, et al.: Infantile Refsum's disease: biochemical findings suggesting multiple peroxisomal dysfunction. J Inherit Metab Dis. 1986;9(2):169-74. [2427795 ]
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023241
KNApSAcK IDNot Available
Chemspider ID21865494
KEGG Compound IDC04722
BioCyc IDCPD-1836
BiGG ID44407
Wikipedia LinkNot Available
NuGOwiki LinkHMDB03873
Metagene LinkHMDB03873
METLIN ID6986
PubChem Compound23657849
PDB IDNot Available
ChEBI ID48043
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Mihalik SJ, Steinberg SJ, Pei Z, Park J, Kim DG, Heinzer AK, Dacremont G, Wanders RJ, Cuebas DA, Smith KD, Watkins PA: Participation of two members of the very long-chain acyl-CoA synthetase family in bile acid synthesis and recycling. J Biol Chem. 2002 Jul 5;277(27):24771-9. Epub 2002 Apr 29. [11980911 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the first step in the oxidation of the side chain of sterol intermediates; the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol. Has also a vitamin D3-25-hydroxylase activity.
Gene Name:
CYP27A1
Uniprot ID:
Q02318
Molecular weight:
60234.28
Reactions
5-b-Cholestane-3a ,7a ,12a-triol + NADPH + Oxygen → 3a,7a,12a-Trihydroxy-5b-cholestanoic acid + NADP + Waterdetails
3a,7a,12a-Trihydroxy-5b-cholestan-26-al + NADPH + Oxygen + Hydrogen Ion → 3a,7a,12a-Trihydroxy-5b-cholestanoic acid + NADP + Waterdetails
General function:
Involved in catalytic activity
Specific function:
Acyl-CoA synthetase involved in bile acid metabolism. Proposed to catalyze the first step in the conjugation of C24 bile acids (choloneates) to glycine and taurine before excretion into bile canaliculi by activating them to their CoA thioesters. Seems to activate secondary bile acids entering the liver from the enterohepatic circulation. In vitro, also activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol.
Gene Name:
SLC27A5
Uniprot ID:
Q9Y2P5
Molecular weight:
75384.375
Reactions
Adenosine triphosphate + 3a,7a,12a-Trihydroxy-5b-cholestanoic acid + Coenzyme A → Adenosine monophosphate + Pyrophosphate + (25R)-3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoAdetails
Adenosine triphosphate + 3a,7a,12a-Trihydroxy-5b-cholestanoic acid + Coenzyme A → Adenosine monophosphate + Pyrophosphate + 3a,7a,12a-Trihydroxy-5b-cholestanoyl-CoAdetails
3a,7a,12a-Trihydroxy-5b-cholestanoic acid + Adenosine triphosphate + Coenzyme A → (25R)-3alpha,7alpha,12alpha-Trihydroxy-5beta-cholestan-26-oyl-CoA + Adenosine monophosphate + Pyrophosphatedetails
General function:
Involved in binding
Specific function:
Ileal protein which stimulates gastric acid and pepsinogen secretion. Seems to be able to bind to bile salts and bilirubins. Isoform 2 is essential for the survival of colon cancer cells to bile acid-induced apoptosis
Gene Name:
FABP6
Uniprot ID:
P51161
Molecular weight:
14371.2
References
  1. Kurz M, Brachvogel V, Matter H, Stengelin S, Thuring H, Kramer W: Insights into the bile acid transportation system: the human ileal lipid-binding protein-cholyltaurine complex and its comparison with homologous structures. Proteins. 2003 Feb 1;50(2):312-28. [12486725 ]

Transporters

General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP)
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular weight:
77402.2
General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular weight:
76448.0
References
  1. Michalski C, Cui Y, Nies AT, Nuessler AK, Neuhaus P, Zanger UM, Klein K, Eichelbaum M, Keppler D, Konig J: A naturally occurring mutation in the SLC21A6 gene causing impaired membrane localization of the hepatocyte uptake transporter. J Biol Chem. 2002 Nov 8;277(45):43058-63. Epub 2002 Aug 23. [12196548 ]
General function:
Involved in ATP binding
Specific function:
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes
Gene Name:
ABCC3
Uniprot ID:
O15438
Molecular weight:
169341.1
General function:
Involved in ATP binding
Specific function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes
Gene Name:
ABCB11
Uniprot ID:
O95342
Molecular weight:
146405.8
General function:
Involved in bile acid:sodium symporter activity
Specific function:
Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism
Gene Name:
SLC10A2
Uniprot ID:
Q12908
Molecular weight:
37697.4
References
  1. Kramer W, Girbig F, Glombik H, Corsiero D, Stengelin S, Weyland C: Identification of a ligand-binding site in the Na+/bile acid cotransporting protein from rabbit ileum. J Biol Chem. 2001 Sep 21;276(38):36020-7. Epub 2001 Jul 10. [11447228 ]
General function:
Involved in bile acid:sodium symporter activity
Specific function:
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presence of sodium.
Gene Name:
SLC10A1
Uniprot ID:
Q14973
Molecular weight:
38118.64
General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids
Gene Name:
SLCO1A2
Uniprot ID:
P46721
Molecular weight:
74144.1
General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and of estrone-3-sulfate and taurocholate
Gene Name:
SLCO4A1
Uniprot ID:
Q96BD0
Molecular weight:
77192.5