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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2006-07-26 10:28:39 UTC
Update Date2020-02-26 21:24:30 UTC
HMDB IDHMDB0003325
Secondary Accession Numbers
  • HMDB0006518
  • HMDB03325
  • HMDB06518
Metabolite Identification
Common NameBilirubin diglucuronide
DescriptionBilirubin diglucuronide is a glucuronidated version of bilirubin, a tetrapyrrole compound produced via heme degradation. Heme is the red pigment in haemoglobin and red blood cells (RBCs). RBCs have a life span of about 120 days. When the RBCs have reached the end of their useful lifespan, the cells are engulfed by macrophages and their constituents recycled or disposed of. Heme is broken down when the heme ring is opened by the enzyme known as heme oxygenase, which is found in the endoplasmic reticulum of the macrophages. The oxidation process produces the linear tetrapyrrole known as biliverdin along with ferric iron (Fe3+), and carbon monoxide (CO). In the next reaction, a second methylene group (located between rings III and IV of the porphyrin ring) is reduced by the enzyme known as biliverdin reductase, producing bilirubin. Bilirubin is significantly less extensively conjugated than biliverdin. This reduction causes a change in the color of the biliverdin molecule from blue-green (vert or verd for green) to yellow-red, which is the color of bilirubin (ruby or rubi for red). In plasma virtually all the bilirubin is tightly bound to plasma proteins, largely albumin, because it is only sparingly soluble in aqueous solutions at physiological pH. In the sinusoids unconjugated bilirubin dissociates from albumin, enters the liver cells across the cell membrane through non-ionic diffusion to the smooth endoplasmatic reticulum. In hepatocytes, bilirubin-UDP-glucuronyltransferase (bilirubin-UGT) adds 2 additional glucuronic acid molecules to bilirubin to produce the more water-soluble version of the molecule known as bilirubin diglucuronide. The bilirubin diglucuronide is transferred rapidly across the canalicular membrane into the bile canaliculi where it is then excreted as bile into the large intestine.
Structure
Data?1582752270
Synonyms
ValueSource
Bilirubin-bisglucuronosideKegg
Bilirubin ixalpha diglucuronideHMDB
Bilirubin ixα diglucuronideHMDB
Bilirubin glucuronideHMDB
Bilirubin diglucuronideMeSH
Chemical FormulaC45H52N4O18
Average Molecular Weight936.921
Monoisotopic Molecular Weight936.32766085
IUPAC Name(2S,3S,4S,5R,6S)-6-{[3-(2-{[3-(3-{[(2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]oxy}-3-oxopropyl)-5-{[(2E)-3-ethenyl-5-hydroxy-4-methyl-2H-pyrrol-2-ylidene]methyl}-4-methyl-1H-pyrrol-2-yl]methyl}-5-{[(2E)-4-ethenyl-5-hydroxy-3-methyl-2H-pyrrol-2-ylidene]methyl}-4-methyl-1H-pyrrol-3-yl)propanoyl]oxy}-3,4,5-trihydroxyoxane-2-carboxylic acid
Traditional Name(2S,3S,4S,5R,6S)-6-{[3-(2-{[3-(3-{[(2S,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]oxy}-3-oxopropyl)-5-{[(2E)-3-ethenyl-5-hydroxy-4-methylpyrrol-2-ylidene]methyl}-4-methyl-1H-pyrrol-2-yl]methyl}-5-{[(2E)-4-ethenyl-5-hydroxy-3-methylpyrrol-2-ylidene]methyl}-4-methyl-1H-pyrrol-3-yl)propanoyl]oxy}-3,4,5-trihydroxyoxane-2-carboxylic acid
CAS Registry Number17459-92-6
SMILES
CC1=C(C=C)\C(NC1=O)=C\C1=C(C)C(CCC(=O)O[C@@H]2O[C@@H]([C@@H](O)[C@H](O)[C@H]2O)C(O)=O)=C(CC2=C(CCC(=O)O[C@@H]3O[C@@H]([C@@H](O)[C@H](O)[C@H]3O)C(O)=O)C(C)=C(N2)\C=C2/NC(=O)C(C=C)=C2C)N1
InChI Identifier
InChI=1S/C45H52N4O18/c1-7-20-19(6)40(58)49-27(20)14-25-18(5)23(10-12-31(51)65-45-37(57)33(53)35(55)39(67-45)43(62)63)29(47-25)15-28-22(17(4)24(46-28)13-26-16(3)21(8-2)41(59)48-26)9-11-30(50)64-44-36(56)32(52)34(54)38(66-44)42(60)61/h7-8,13-14,32-39,44-47,52-57H,1-2,9-12,15H2,3-6H3,(H,48,59)(H,49,58)(H,60,61)(H,62,63)/b26-13-,27-14-/t32-,33-,34-,35-,36+,37+,38-,39-,44+,45+/m0/s1
InChI KeySCJLWMXOOYZBTH-BTVQFETGSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as bilirubins. These are organic compounds containing a dicarboxylic acyclic tetrapyrrole derivative.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassTetrapyrroles and derivatives
Sub ClassBilirubins
Direct ParentBilirubins
Alternative Parents
Substituents
  • Bilirubin skeleton
  • O-glucuronide
  • 1-o-glucuronide
  • Tetracarboxylic acid or derivatives
  • Glucuronic acid or derivatives
  • Beta-hydroxy acid
  • Fatty acid ester
  • Monosaccharide
  • Oxane
  • Pyran
  • Substituted pyrrole
  • Fatty acyl
  • Hydroxy acid
  • Pyrroline
  • Pyrrole
  • Heteroaromatic compound
  • Secondary alcohol
  • Secondary carboxylic acid amide
  • Carboxylic acid ester
  • Lactam
  • Carboxamide group
  • Acetal
  • Carboxylic acid derivative
  • Carboxylic acid
  • Oxacycle
  • Azacycle
  • Polyol
  • Organic oxide
  • Alcohol
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Ontology
Disposition

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

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 Solubility0.13 g/LALOGPS
logP1.32ALOGPS
logP-1.7ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)2.9ChemAxon
pKa (Strongest Basic)4.4ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count18ChemAxon
Hydrogen Donor Count12ChemAxon
Polar Surface Area363.8 ŲChemAxon
Rotatable Bond Count18ChemAxon
Refractivity234.54 m³·mol⁻¹ChemAxon
Polarizability97.04 ųChemAxon
Number of Rings6ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00kf-0200030903-3f731d3255f730a58952Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-016u-0300070902-a0595a946705461ddb24Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0059-2200094431-2cedb95f9845511ac143Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-052f-0200025912-c488140c352914da3532Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00kf-2800020923-c9e3902c3b856732b595Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01r7-6900003740-e2aa55faca0003c1270fSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biospecimen Locations
  • Blood
  • Urine
Tissue Locations
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableNormal
      Not Available
details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableNormal
      Not Available
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4444368
KEGG Compound IDC05787
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkBilirubin diglucuronide
METLIN IDNot Available
PubChem Compound5280817
PDB IDNot Available
ChEBI IDNot Available
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Mshelia DS, Buba AA: Point of care testing: a delight or a dilemma in the developing world?: an overview. Niger Postgrad Med J. 2005 Jun;12(2):136-9. [PubMed:15997265 ]
  2. Luo J, Lim CK: Isolation and characterization of new porphyrin metabolites in human porphyria cutanea tarda and in rats treated with hexachlorobenzene by HPTLC, HPLC and liquid secondary ion mass spectrometry. Biomed Chromatogr. 1995 May-Jun;9(3):113-22. [PubMed:7655298 ]
  3. Fevery J, Blanckaert N, Leroy P, Michiels R, Heirwegh KP: Analysis of bilirubins in biological fluids by extraction and thin-layer chromatography of the intact tetrapyrroles: application to bile of patients with Gilbert's syndrome, hemolysis, or cholelithiasis. Hepatology. 1983 Mar-Apr;3(2):177-83. [PubMed:6832709 ]
  4. Chowdhury JR, Chowdhury NR, Wu G, Shouval R, Arias IM: Bilirubin mono- and diglucuronide formation by human liver in vitro: assay by high-pressure liquid chromatography. Hepatology. 1981 Nov-Dec;1(6):622-7. [PubMed:6796486 ]
  5. Goresky CA, Gordon ER, Hinchey EJ, Fried GM: Bilirubin conjugate changes in the bile of gallbladders containing gallstones. Hepatology. 1995 Feb;21(2):373-82. [PubMed:7843708 ]

Only showing the first 10 proteins. There are 22 proteins in total.

Enzymes

General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme has glucuronidating capacity with steroid substrates such as 5-beta-androstane 3-alpha,17-beta-diol, estradiol, ADT, eugenol and bile acids. Only isoform 1 seems to be active.
Gene Name:
UGT2B28
Uniprot ID:
Q9BY64
Molecular weight:
38742.9
Reactions
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronidedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as estriol, 4-hydroxyestrone and 2-hydroxyestriol) and xenobiotics (such as 4-methylumbelliferone, 1-naphthol, 4-nitrophenol, 2-aminophenol, 4-hydroxybiphenyl and menthol). It is capable of 6 alpha-hydroxyglucuronidation of hyodeoxycholic acid.
Gene Name:
UGT2B4
Uniprot ID:
P06133
Molecular weight:
60512.035
Reactions
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronidedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate.
Gene Name:
UGT1A4
Uniprot ID:
P22310
Molecular weight:
60024.535
Reactions
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronidedetails
References
  1. Meunier CJ, Verbeeck RK: Glucuronidation of R- and S-ketoprofen, acetaminophen, and diflunisal by liver microsomes of adjuvant-induced arthritic rats. Drug Metab Dispos. 1999 Jan;27(1):26-31. [PubMed:9884306 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT2B10
Uniprot ID:
P36537
Molecular weight:
60773.485
Reactions
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronidedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol (in vitro).
Gene Name:
UGT2B7
Uniprot ID:
P16662
Molecular weight:
60720.15
Reactions
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronidedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xenobiotic substrates, including simple phenolic compounds, 7-hydroxylated coumarins, flavonoids, anthraquinones, and certain drugs and their hydroxylated metabolites. It also catalyzes the glucuronidation of endogenous estrogens and androgens.
Gene Name:
UGT2B15
Uniprot ID:
P54855
Molecular weight:
61035.815
Reactions
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronidedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Active on odorants and seems to be involved in olfaction; it could help clear lipophilic odorant molecules from the sensory epithelium.
Gene Name:
UGT2A1
Uniprot ID:
Q9Y4X1
Molecular weight:
60771.605
Reactions
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronidedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone.
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular weight:
59590.91
Reactions
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronidedetails
References
  1. Meunier CJ, Verbeeck RK: Glucuronidation of R- and S-ketoprofen, acetaminophen, and diflunisal by liver microsomes of adjuvant-induced arthritic rats. Drug Metab Dispos. 1999 Jan;27(1):26-31. [PubMed:9884306 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular weight:
59940.495
Reactions
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronidedetails
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
Gene Name:
UGT1A8
Uniprot ID:
Q9HAW9
Molecular weight:
59741.035
Reactions
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronidedetails

Only showing the first 10 proteins. There are 22 proteins in total.