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Record Information
Version3.6
Creation Date2013-05-17 01:22:40 UTC
Update Date2016-02-11 08:06:25 UTC
HMDB IDHMDB60464
Secondary Accession NumbersNone
Metabolite Identification
Common NameCodeine-6-glucuronide
DescriptionCodeine-6-glucuronide (C6G) is a major active metabolite of codeine and may be responsible for as much as 60% of the analgesic effects of codeine. C6G exhibits decreased immunosuppressive effects compared to codeine. During its metabolism, codeine is conjugated with glucuronic acid by the enzyme UDP-Glucuronosyltransferase-2B7 (UGT2B7) to form codeine-6-glucuronide. (Wikipedia)
Structure
Thumb
Synonyms
ValueSource
C16577HMDB
Codeine glucuronideHMDB
Glucopyranosiduronic acid, codeine, b-D- (6ci)HMDB
Glucopyranosiduronicacid, 7,8-didehydro-4,5a-epoxy-3-methoxy-17-methylmorphinan-6a-yl, b-D- (8ci)HMDB
Morphinan, 7,8-didehydro-4,5a-epoxy-6a-(b-D-glucopyranuronosyloxy)-3-methoxy-17-methyl- (8ci)HMDB
Chemical FormulaC24H29NO9
Average Molecular Weight475.4884
Monoisotopic Molecular Weight475.184231531
IUPAC Name(2S,3S,4S,5R,6R)-3,4,5-trihydroxy-6-{[(1S,5R,13R,14S,17R)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7,9,11(18),15-tetraen-14-yl]oxy}oxane-2-carboxylic acid
Traditional Namecodeine-6-glucuronide
CAS Registry Number20736-11-2
SMILES
[H][C@]12C=C[C@H](O[C@@H]3O[C@@H]([C@@H](O)[C@H](O)[C@H]3O)C(O)=O)[C@@H]3OC4=C5C(C[C@H]1N(C)CC[C@@]235)=CC=C4OC
InChI Identifier
InChI=1S/C24H29NO9/c1-25-8-7-24-11-4-6-14(32-23-18(28)16(26)17(27)20(34-23)22(29)30)21(24)33-19-13(31-2)5-3-10(15(19)24)9-12(11)25/h3-6,11-12,14,16-18,20-21,23,26-28H,7-9H2,1-2H3,(H,29,30)/t11-,12+,14-,16-,17-,18+,20-,21-,23+,24-/m0/s1
InChI KeyInChIKey=CRWVOYRJXPDBPM-HSCJLHHPSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassMorphinans
Sub ClassNot Available
Direct ParentMorphinans
Alternative Parents
Substituents
  • Morphinan
  • Benzylisoquinoline
  • Phenanthrene
  • O-glucuronide
  • 1-o-glucuronide
  • Glucuronic acid or derivatives
  • O-glycosyl compound
  • Glycosyl compound
  • Tetralin
  • Pyran carboxylic acid
  • Pyran carboxylic acid or derivatives
  • Benzofuran
  • Anisole
  • Aralkylamine
  • Beta-hydroxy acid
  • Alkyl aryl ether
  • Benzenoid
  • Pyran
  • Piperidine
  • Oxane
  • Monosaccharide
  • Hydroxy acid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Polyol
  • 1,2-diol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Acetal
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
StatusDetected but not Quantified
Origin
  • Drug metabolite
Biofunction
  • Analgesic
  • Waste products
ApplicationNot Available
Cellular locations
  • Microsomes
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point248-250°Chttp://www.buyersguidechem.com/cas_supplier/20736-11-2.html
Boiling PointNot AvailableNot Available
Water SolubilityHighToronto Research Chemicals, 2013
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility4.31 mg/mLALOGPS
logP-0.23ALOGPS
logP-2.8ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)2.87ChemAxon
pKa (Strongest Basic)9.19ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area138.15 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity116.89 m3·mol-1ChemAxon
Polarizability47.27 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Microsomes
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Kidney
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Codeine Metabolism PathwaySMP00621Not Available
Codeine PathwaySMP00405Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
UrineDetected but not QuantifiedNot ApplicableNot AvailableNot Available
collected 0–6 h after oral intake of 60 mg of codeine
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot ApplicableNot SpecifiedNot SpecifiedArrested for driving under the influence of drugs. details
BloodDetected but not QuantifiedNot ApplicableNot SpecifiedNot Specifiedfemoral vein blood in a typical case of fatal heroin overdose. details
UrineDetected but not QuantifiedNot ApplicableNot SpecifiedFemale
Heroine addict
details
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDDBMET00660
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4590054
KEGG Compound IDC16577
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia Linkhttp://en.wikipedia.org/wiki/Codeine-6-glucuronide
NuGOwiki LinkHMDB60464
Metagene LinkHMDB60464
METLIN IDNot Available
PubChem Compound5489029
PDB IDNot Available
ChEBI IDNot Available
References
Synthesis ReferenceSrinivasan, Vinayak; Wielbo, Donna; Simpkins, James; Karlix, Janet; Sloan, Kenneth; Tebbett, Ian, 1996: Analgesic and immunomodulatory effects of codeine and codeine 6-glucuronide. Pharmaceutical Research (new York). 13(2): 296-300
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Murphy CM, Huestis MA: LC-ESI-MS/MS analysis for the quantification of morphine, codeine, morphine-3-beta-D-glucuronide, morphine-6-beta-D-glucuronide, and codeine-6-beta-D-glucuronide in human urine. J Mass Spectrom. 2005 Nov;40(11):1412-6. [16258895 ]
  2. Magrane M, Consortium U: UniProt Knowledgebase: a hub of integrated protein data. Database (Oxford). 2011 Mar 29;2011:bar009. doi: 10.1093/database/bar009. Print 2011. [21447597 ]
  3. Srinivasan V, Wielbo D, Tebbett IR: Analgesic effects of codeine-6-glucuronide after intravenous administration. Eur J Pain. 1997;1(3):185-90. [15102399 ]
  4. Vree TB, van Dongen RT, Koopman-Kimenai PM: Codeine analgesia is due to codeine-6-glucuronide, not morphine. Int J Clin Pract. 2000 Jul-Aug;54(6):395-8. [11092114 ]
  5. Raungrut P, Uchaipichat V, Elliot DJ, Janchawee B, Somogyi AA, Miners JO: In vitro-in vivo extrapolation predicts drug-drug interactions arising from inhibition of codeine glucuronidation by dextropropoxyphene, fluconazole, ketoconazole, and methadone in humans. J Pharmacol Exp Ther. 2010 Aug;334(2):609-18. doi: 10.1124/jpet.110.167916. Epub 2010 May 18. [20484152 ]
  6. Bogusz MJ, Maier RD, Erkens M, Driessen S: Determination of morphine and its 3- and 6-glucuronides, codeine, codeine-glucuronide and 6-monoacetylmorphine in body fluids by liquid chromatography atmospheric pressure chemical ionization mass spectrometry. J Chromatogr B Biomed Sci Appl. 1997 Dec 5;703(1-2):115-27. [9448068 ]

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 + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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 + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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 + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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 + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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 + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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 + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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 + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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 + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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 + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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 + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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:
UGT1A3
Uniprot ID:
P35503
Molecular weight:
60337.835
Reactions
Uridine diphosphate glucuronic acid + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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:
UGT1A10
Uniprot ID:
Q9HAW8
Molecular weight:
59809.075
Reactions
Uridine diphosphate glucuronic acid + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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. The major substrates of this isozyme are eugenol > 4-methylumbelliferone > dihydrotestosterone (DHT) > androstane-3-alpha,17-beta-diol (3-alpha-diol) > testosterone > androsterone (ADT).
Gene Name:
UGT2B17
Uniprot ID:
O75795
Molecular weight:
61094.915
Reactions
Uridine diphosphate glucuronic acid + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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:
UGT1A6
Uniprot ID:
P19224
Molecular weight:
60750.215
Reactions
Uridine diphosphate glucuronic acid + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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:
UGT1A5
Uniprot ID:
P35504
Molecular weight:
60070.565
Reactions
Uridine diphosphate glucuronic acid + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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:
UGT2B11
Uniprot ID:
O75310
Molecular weight:
61037.8
Reactions
Uridine diphosphate glucuronic acid + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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:
UGT1A7
Uniprot ID:
Q9HAW7
Molecular weight:
59818.315
Reactions
Uridine diphosphate glucuronic acid + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails
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 (By similarity).
Gene Name:
UGT2A3
Uniprot ID:
Q6UWM9
Molecular weight:
60253.94
Reactions
Uridine diphosphate glucuronic acid + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronidedetails