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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-13 11:48:54 UTC
Update Date2019-07-23 06:35:16 UTC
HMDB IDHMDB0041937
Secondary Accession Numbers
  • HMDB41937
Metabolite Identification
Common NameMorphine-6-glucuronide
DescriptionMorphine-6-glucuronide belongs to the class of organic compounds known as halopyrimidines. These are aromatic compounds containing a halogen atom linked to a pyrimidine ring. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions. Morphine-6-glucuronide (M6G) is a major active metabolite of morphine, and as such is the molecule responsible for much of the pain-relieving effects of morphine and heroin. It has analgesic effects more potent than morphine. Morphine-6-glucuronide is a very strong basic compound (based on its pKa). morphine-6-glucuronide and uridine 5'-diphosphate can be biosynthesized from morphine and uridine diphosphate glucuronic acid through the action of the enzymes UDP-glucuronosyltransferase 1-8, UDP-glucuronosyltransferase 1-1, UDP-glucuronosyltransferase 1-3, UDP-glucuronosyltransferase 2B4, UDP-glucuronosyltransferase 2B7, and UDP-glucuronosyltransferase 2B15. In humans, morphine-6-glucuronide is involved in morphine action pathway. The first studies demonstrated massive levels of M6G in 3 patients with renal failure, which resolved as kidney function returned. A key step in defining the importance of M6G in humans came in 1992 when the substance was artificially synthesised and administered to patients with pain, the majority of whom described pain relief. This analgesic activity of M6G (in animals) was first noted by Yoshimura. Subsequent work at St Bartholomew's Hospital, London in the 1980s, using a sensitive and specific HPLC assay, accurately defined for the first time the metabolism of morphine, and the abundance of this metabolite (along with morphine-3-glucuronide, considered an inactive metabolite). M6G is formed from morphine by the enzyme UGT2B7. The frequent use of morphine in critically ill patients, and the common occurrence of kidney failure in this group implied that M6G accumulation could be a common, but previously unanticipated problem. Accumulation of M3G and M6G also decrease with return of kidney function after kidney transplantation. M6G can accumulate to toxic levels in kidney failure. It was postulated that kidney impairment would result in accumulation of the kidney-excreted active agent M6G, leading to potentially fatal toxicity such as respiratory depression.
Structure
Data?1563863716
Synonyms
ValueSource
Morphine 6-glucuronide(minor)HMDB
Morphine-6beta-glucuronideHMDB
Chemical FormulaC23H27NO9
Average Molecular Weight461.4618
Monoisotopic Molecular Weight461.168581467
IUPAC Name(2S,3S,4S,5R,6R)-3,4,5-trihydroxy-6-{[(1S,5R,13R,14S,17R)-10-hydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10,15-tetraen-14-yl]oxy}oxane-2-carboxylic acid
Traditional Namemorphine-6-glucuronide
CAS Registry Number20290-10-2
SMILES
CN1CC[C@]23[C@H]4OC5=C(O)C=CC(C[C@@H]1[C@@H]2C=C[C@@H]4O[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)C(O)=O)=C35
InChI Identifier
InChI=1S/C23H27NO9/c1-24-7-6-23-10-3-5-13(31-22-17(28)15(26)16(27)19(33-22)21(29)30)20(23)32-18-12(25)4-2-9(14(18)23)8-11(10)24/h2-5,10-11,13,15-17,19-20,22,25-28H,6-8H2,1H3,(H,29,30)/t10-,11+,13-,15-,16-,17+,19-,20-,22+,23-/m0/s1
InChI KeyGNJCUHZOSOYIEC-GAROZEBRSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as halopyrimidines. These are aromatic compounds containing a halogen atom linked to a pyrimidine ring. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentHalopyrimidines
Alternative Parents
Substituents
  • Alkyl aryl ether
  • Aminopyrimidine
  • Halopyrimidine
  • Aryl chloride
  • Aryl halide
  • Heteroaromatic compound
  • 2-imidazoline
  • Guanidine
  • Ether
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organohalogen compound
  • Organochloride
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
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 Solubility9.19 g/LALOGPS
logP0.13ALOGPS
logP-3ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)2.87ChemAxon
pKa (Strongest Basic)9.12ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area149.15 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity112.4 m³·mol⁻¹ChemAxon
Polarizability45.1 ųChemAxon
Number of Rings6ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-052f-9202300000-ce7f33f04f8cff4d7effSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-03di-6422029000-6bee985a88b2cded541eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-01pc-0090600000-76fa4c9250ebcf13af84Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0090000000-3005feb91497a08f8b36Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05ui-1190000000-872ff3b2a3e6f5183be9Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03e9-2351900000-c08d50450513534759cfSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-1290200000-88dbeea3f240b83f14d3Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-3190000000-75a39cff401f565b20b5Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
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 ID4514548
KEGG Compound IDC16578
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMorphine-6-glucuronide
METLIN IDNot Available
PubChem Compound5360621
PDB IDNot Available
ChEBI IDNot Available
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Only showing the first 10 proteins. There are 18 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
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphatedetails
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
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphatedetails
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
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphatedetails
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
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphatedetails
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
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphatedetails
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
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphatedetails
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
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphatedetails
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
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphatedetails
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
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphatedetails
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
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphatedetails

Only showing the first 10 proteins. There are 18 proteins in total.