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Human Metabolome Database Version 3.5

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Showing metabocard for Hydroxycotinine (HMDB01390)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-02-08 17:10:27 -0700
HMDB ID HMDB01390
Secondary Accession Numbers None
Metabolite Identification
Common Name Hydroxycotinine
Description Quantitatively, the most important metabolite of nicotine in most mammalian species is cotinine. In humans, about 70 to 80% of nicotine is converted to cotinine. 3-Hydroxycotinine (3HC) is the main nicotine metabolite detected in smokers urine. It is also excreted as a glucuronide conjugate (3HC-Gluc). 3HC and 3HC-Gluc account for 40-60% of the nicotine dose in urine.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. (3R-trans)-3-hydroxy-1-methyl-5-(3-pyridinyl)-2-Pyrrolidinone
  2. 3-Hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone
  3. 3-Hydroxycotinine
  4. trans-3'-Hydroxycotinine
  5. trans-3-Hydroxycotinine
Chemical Formula C10H12N2O2
Average Molecular Weight 192.2145
Monoisotopic Molecular Weight 192.089877638
IUPAC Name (5S)-3-hydroxy-1-methyl-5-(pyridin-3-yl)pyrrolidin-2-one
Traditional IUPAC Name (5S)-3-hydroxy-1-methyl-5-(pyridin-3-yl)pyrrolidin-2-one
CAS Registry Number 34834-67-8
SMILES CN1[C@@H](CC(O)C1=O)C1=CN=CC=C1
InChI Identifier InChI=1S/C10H12N2O2/c1-12-8(5-9(13)10(12)14)7-3-2-4-11-6-7/h2-4,6,8-9,13H,5H2,1H3/t8-,9?/m0/s1
InChI Key XOKCJXZZNAUIQN-IENPIDJESA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Alkaloids and Derivatives
Class N/A
Sub Class N/A
Other Descriptors
  • Pyrrolidinylpyridines
Substituents
  • Carboxamide Group
  • Lactam
  • Pyridine
  • Pyrrolidine
  • Pyrrolidone
  • Secondary Alcohol
  • Tertiary Carboxylic Acid Amide
Direct Parent Alkaloids and Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction Not Available
Application Not Available
Cellular locations
  • Cytoplasm (predicted from logP)
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point Not Available Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP -1.45 LI,NY & GORROD,JW (1992)
Predicted Properties
Property Value Source
Water Solubility 47.7 g/L ALOGPS
LogP -0.32 ALOGPS
LogP -0.73 ChemAxon
LogS -0.61 ALOGPS
pKa (strongest acidic) 13.11 ChemAxon
pKa (strongest basic) 4.79 ChemAxon
Hydrogen Acceptor Count 3 ChemAxon
Hydrogen Donor Count 1 ChemAxon
Polar Surface Area 53.43 A2 ChemAxon
Rotatable Bond Count 1 ChemAxon
Refractivity 50.73 ChemAxon
Polarizability 19.48 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 0 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Cytoplasm (predicted from logP)
Biofluid Locations
  • Blood
  • Saliva
  • Urine
Tissue Location
  • Liver
Pathways Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Comments
Blood Detected and Quantified
Article_icon
0.35 +/- 0.15 uM Adult (>18 years old) Both Normal Not Available
Blood Detected and Quantified
Article_icon
0.25 +/- 0.045 uM Adult (>18 years old) Both Normal Not Available
Saliva Detected and Quantified
Article_icon
<1.00 uM Adult (>18 years old) Both Normal Not Available
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Comments
Blood Detected and Quantified
Article_icon
1.5 (0.52-2.6) uM Adult (>18 years old) Both Active tobacco user Not Available
Urine Detected and Quantified
Article_icon
4.5 (1.0-8.5) umol/mmol creatinine Adult (>18 years old) Both Active tobacco user Not Available
Associated Disorders and Diseases
Disease References
Smoking
  • Zuccaro P, Altieri I, Rosa M, Passa AR, Pichini S, Ricciarello G, Pacifici R: Determination of nicotine and four metabolites in the serum of smokers by high-performance liquid chromatography with ultraviolet detection. J Chromatogr. 1993 Nov 24;621(2):257-61. Pubmed: 8294547 Link_out
  • Moyer TP, Charlson JR, Enger RJ, Dale LC, Ebbert JO, Schroeder DR, Hurt RD: Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in serum or urine by tandem mass spectrometry, with clinically relevant metabolic profiles. Clin Chem. 2002 Sep;48(9):1460-71. Pubmed: 12194923 Link_out
    Associated OMIM IDs None
    DrugBank ID Not Available
    Phenol Explorer Compound ID Not Available
    Phenol Explorer Metabolite ID Not Available
    FoodDB ID FDB022597
    KNApSAcK ID Not Available
    Chemspider ID 8395266 Link_out
    KEGG Compound ID Not Available
    BioCyc ID CPD-2750 Link_out
    BiGG ID Not Available
    Wikipedia Link Not Available
    NuGOwiki Link HMDB01390 Link_out
    Metagene Link HMDB01390 Link_out
    METLIN ID 6210 Link_out
    PubChem Compound 10219774 Link_out
    PDB ID Not Available
    ChEBI ID Not Available
    References
    Synthesis Reference Jacob, Peyton, III; Shulgin, Alexander T.; Benowitz, Neal L. Synthesis of (3'R,5'S)-trans-3'-hydroxycotinine, a major metabolite of nicotine. Metabolic formation of 3'-hydroxycotinine in humans is highly stereoselective. Journal of Medicinal Chemistry (19
    Material Safety Data Sheet (MSDS) Download (PDF)
    General References
    1. Bentley MC, Abrar M, Kelk M, Cook J, Phillips K: Validation of an assay for the determination of cotinine and 3-hydroxycotinine in human saliva using automated solid-phase extraction and liquid chromatography with tandem mass spectrometric detection. J Chromatogr B Biomed Sci Appl. 1999 Feb 19;723(1-2):185-94. Pubmed: 10080645 Link_out
    2. Pacifici R, Pichini S, Altieri I, Rosa M, Bacosi A, Caronna A, Zuccaro P: Determination of nicotine and two major metabolites in serum by solid-phase extraction and high-performance liquid chromatography, and high-performance liquid chromatography-particle beam mass spectrometry. J Chromatogr. 1993 Feb 26;612(2):209-13. Pubmed: 8468378 Link_out
    3. Moyer TP, Charlson JR, Enger RJ, Dale LC, Ebbert JO, Schroeder DR, Hurt RD: Simultaneous analysis of nicotine, nicotine metabolites, and tobacco alkaloids in serum or urine by tandem mass spectrometry, with clinically relevant metabolic profiles. Clin Chem. 2002 Sep;48(9):1460-71. Pubmed: 12194923 Link_out
    4. Tuomi T, Johnsson T, Reijula K: Analysis of nicotine, 3-hydroxycotinine, cotinine, and caffeine in urine of passive smokers by HPLC-tandem mass spectrometry. Clin Chem. 1999 Dec;45(12):2164-72. Pubmed: 10585349 Link_out
    5. Lerman C, Tyndale R, Patterson F, Wileyto EP, Shields PG, Pinto A, Benowitz N: Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation. Clin Pharmacol Ther. 2006 Jun;79(6):600-8. Epub 2006 May 11. Pubmed: 16765148 Link_out
    6. Kim I, Huestis MA: A validated method for the determination of nicotine, cotinine, trans-3'-hydroxycotinine, and norcotinine in human plasma using solid-phase extraction and liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. J Mass Spectrom. 2006 Jun;41(6):815-21. Pubmed: 16705667 Link_out
    7. Xu X, Iba MM, Weisel CP: Simultaneous and sensitive measurement of anabasine, nicotine, and nicotine metabolites in human urine by liquid chromatography-tandem mass spectrometry. Clin Chem. 2004 Dec;50(12):2323-30. Epub 2004 Oct 7. Pubmed: 15472033 Link_out
    Enzymes
    Name: UDP-glucuronosyltransferase 2B4
    Reactions:
    • UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside [RN:R01383]
    Gene Name: UGT2B4
    Uniprot ID: P06133 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    Name: UDP-glucuronosyltransferase 1-4
    Reactions:
    • UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside [RN:R01383]
    Gene Name: UGT1A4
    Uniprot ID: P22310 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    Name: UDP-glucuronosyltransferase 2B7
    Reactions:
    • UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside [RN:R01383]
    Gene Name: UGT2B7
    Uniprot ID: P16662 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    Name: UDP-glucuronosyltransferase 1-9
    Reactions:
    • UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside [RN:R01383]
    Gene Name: UGT1A9
    Uniprot ID: O60656 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA