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Human Metabolome Database Version 3.5

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Showing metabocard for p-Cresol (HMDB01858)

Record Information
Version 3.5
Creation Date 2006-02-22 03:50:16 -0700
Update Date 2013-05-29 13:32:33 -0600
HMDB ID HMDB01858
Secondary Accession Numbers None
Metabolite Identification
Common Name p-Cresol
Description p-Cresol (4-methylphenol), a 108.1 Da volatile low-molecular-weight compound, is a phenol. It is a partially lipophilic moiety which strongly binds to plasma protein (close to 100%) under normal conditions. p-Cresol is metabolized through conjugation, mainly sulphation and glucuronization, but removal of the unconjugated p-cresol is, at least in part, via the urine. Therefore it is not surprising that this compound, together with several other phenoles, is retained when the kidneys fail. P-Cresol is an end-product of protein breakdown, and an increase of the nutritional protein load in healthy individuals results in enhanced generation and urinary excretion. The serum p-cresol concentration in uremic patients can be decreased by changing to a low-protein diet. p-Cresol is one of the metabolites of the amino acid tyrosine, and to a certain extent also of phenylalanine, which are converted to 4-hydroxyphenylacetic acid by intestinal bacteria, before being decarboxylated to p-cresol (putrefaction). The main contributing bacteria are aerobes (mainly enterobacteria), but to a certain extent also anaerobes play a role (mainly Clostridium perfringens). In uremia, modifications in the intestinal flora result in the specific overgrowth of bacteria that are specific p-cresol producers. The administration of antibiotics reduces urinary excretion of p-cresol, as a result of the liquidation of the producing bacteria. Environmental factors might also contribute. The liver cytochrome P450 metabolizes toluene to benzyl alcohol, but also to o-cresol and p-cresol. Toluene is not only used industrially, but it is also the most widely abusively inhaled solvent. Furthermore, p-cresol is a metabolite of menthofuran, one of the metabolites of R-(+)-pulegone, which is found in extracts from the plants Mentha pulegium and Hedeoma pulegioides, commonly known as pennyroyal oil and pennyroyal tea. These extracts are popular as unconventional herbal therapeutic agents and are applied as abortiva, diaphoretics, emmenagogues, and psychedelic drugs. Pennyroyal oil is extensively used for its pleasant mint-like smell in the flavoring industry. The toxicity of pennyroyal oil and menthofuran is well known. Another compound used in traditional medicine, especially in Japan, which is a precursor of p-cresol is wood tar creosote. p-Cresol has been reported to affect several biochemical, biological and physiological functions: (i) it diminishes the oxygen uptake of rat cerebral cortex slices; (ii) it increases the free active drug concentration of warfarin and diazepam; (iii) it has been related to growth retardation in the weanling pig; (iv) it alters cell membrane permeability, at least in bacteria; (v) it induces LDH leakage from rat liver slices; (vi) it induces susceptibility to auditive epileptic crises; and (vii) it blocks cell K+ channels. (PMID: 10570076 Link_out). p-Cresol is a uremic toxin that is at least partially removed by peritoneal dialysis in haemodialysis patients, and has been involved in the progression of renal failure. (MID: 11169029). At concentrations encountered during uremia, p-cresol inhibits phagocyte function and decreases leukocyte adhesion to cytokine-stimulated endothelial cells. (PMID: 14681860 Link_out).
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. 1-Hydroxy-4-methylbenzene
  2. 1-Methyl-4-hydroxybenzene
  3. 4-(Pentafluorosulfanyl)phenol
  4. 4-Cresol
  5. 4-Hydroxytoluene
  6. 4-Methyl phenol
  7. 4-Methylphenol
  8. p-Cresol
  9. p-Cresol 98+ %
  10. p-Cresol Hydrate 90 %
  11. p-Cresylate
  12. p-Cresylic acid
  13. p-Hydroxytoluene
  14. p-Kresol
  15. p-Methyl phenol
  16. p-Methylhydroxybenzene
  17. p-Oxytoluene
  18. p-Toluol
  19. p-Tolyl alcohol
  20. Paracresol
  21. Paramethyl phenol
Chemical Formula C7H8O
Average Molecular Weight 108.1378
Monoisotopic Molecular Weight 108.057514878
IUPAC Name 4-methylphenol
Traditional IUPAC Name P-cresol
CAS Registry Number 106-44-5
SMILES CC1=CC=C(O)C=C1
InChI Identifier InChI=1S/C7H8O/c1-6-2-4-7(8)5-3-6/h2-5,8H,1H3
InChI Key IWDCLRJOBJJRNH-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Aromatic Homomonocyclic Compounds
Class Phenols and Derivatives
Sub Class Cresols
Other Descriptors
  • Aromatic Homomonocyclic Compounds
  • a methylphenol(Cyc)
  • cresol(ChEBI)
Substituents
  • Toluene
Direct Parent Para Cresols
Ontology
Status Detected and Quantified
Origin
  • Endogenous
  • Microbial
Biofunction Not Available
Application Not Available
Cellular locations Not Available
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 35.5 °C Not Available
Boiling Point Not Available Not Available
Water Solubility 21.5 mg/mL at 25 °C Not Available
LogP 1.94 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
Water Solubility 23.1 g/L ALOGPS
LogP 1.95 ALOGPS
LogP 2.18 ChemAxon
LogS -0.67 ALOGPS
pKa (strongest acidic) 10.36 ChemAxon
pKa (strongest basic) -5.4 ChemAxon
Hydrogen Acceptor Count 1 ChemAxon
Hydrogen Donor Count 1 ChemAxon
Polar Surface Area 20.23 A2 ChemAxon
Rotatable Bond Count 0 ChemAxon
Refractivity 33.08 ChemAxon
Polarizability 11.93 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge 0 ChemAxon
Spectra
Gas-MS Spectrum
1H NMR Spectrum
MS/MS Spectrum Quattro_QQQ 10
MS/MS Spectrum Quattro_QQQ 25
MS/MS Spectrum Quattro_QQQ 40
MS/MS Spectrum EI-B (VARIAN MAT-44)
MS/MS Spectrum EI-B (HITACHI RMU-7M)
MS/MS Spectrum EI-B (JEOL JMS-D-3000)
MS/MS Spectrum EI-B (HITACHI M-80B)
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations Not Available
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Fibroblasts
  • Adipose Tissue
Pathways Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Expected but not Quantified
Not Applicable Not Available Not Available Comment Normal
Urine Detected and Quantified
17.6 (17.6-17.6) umol/mmol creatinine Newborn (0-30 days old) Both Normal
Urine Detected and Quantified
24.7 (1.2-110.7) umol/mmol creatinine Children (1-13 year old) Both Comment Normal
Urine Detected and Quantified
46.0 (1.2-118.9) umol/mmol creatinine Adult (>18 years old) Both Comment Normal
Urine Detected and Quantified
23.0 (11.4-114.0) umol/mmol creatinine Adolescent (13-18 years old) Both Comment Normal
Urine Detected and Quantified
0.13 umol/mmol creatinine Adult (>18 years old) Both Normal
Urine Detected but not Quantified
Not Applicable Adult (>18 years old) Both Comment Normal
  • Bouatra, S. ...
Urine Detected and Quantified
52.6 (38.8-71.0) umol/mmol creatinine Adult (>18 years old) Both Normal
  • Geigy Scient...
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified 9.9 +/- 5.1 uM Adult (>18 years old) Both Hemodialysis
Associated Disorders and Diseases
Disease References
Hemodialysis
  • De Smet R, Van Kaer J, Liebich H, Lesaffer G, Verstraete A, Dhondt A, Duym P, Lameire N, Vanholder R: Heparin-induced release of protein-bound solutes during hemodialysis is an in vitro artifact. Clin Chem. 2001 May;47(5):901-9. Pubmed: 11325895 Link_out
    Associated OMIM IDs None
    DrugBank ID DB01688 Link_out
    DrugBank Metabolite ID Not Available
    Phenol Explorer Compound ID Not Available
    Phenol Explorer Metabolite ID Not Available
    FoodDB ID FDB008789
    KNApSAcK ID C00002645 Link_out
    Chemspider ID 13839082 Link_out
    KEGG Compound ID C01468 Link_out
    BioCyc ID CPD-108 Link_out
    BiGG ID Not Available
    Wikipedia Link p-Cresol Link_out
    NuGOwiki Link HMDB01858 Link_out
    Metagene Link HMDB01858 Link_out
    METLIN ID 4236 Link_out
    PubChem Compound 2879 Link_out
    PDB ID PCR Link_out
    ChEBI ID 17847 Link_out
    References
    Synthesis Reference Not Available
    Material Safety Data Sheet (MSDS) Download (PDF)
    General References
    1. Cork A, Park KC: Identification of electrophysiologically-active compounds for the malaria mosquito, Anopheles gambiae, in human sweat extracts. Med Vet Entomol. 1996 Jul;10(3):269-76. Pubmed: 8887339 Link_out
    2. Bone E, Tamm A, Hill M: The production of urinary phenols by gut bacteria and their possible role in the causation of large bowel cancer. Am J Clin Nutr. 1976 Dec;29(12):1448-54. Pubmed: 826152 Link_out
    3. Buhlmann P, Hayakawa M, Ohshiro T, Amemiya S, Umezawa Y: Influence of natural, electrically neutral lipids on the potentiometric responses of cation-selective polymeric membrane electrodes. Anal Chem. 2001 Jul 15;73(14):3199-205. Pubmed: 11476216 Link_out
    4. Akasaka K, Ohrui H, Meguro H, Tamura M: Determination of triacylglycerol and cholesterol ester hydroperoxides in human plasma by high-performance liquid chromatography with fluorometric postcolumn detection. J Chromatogr. 1993 Aug 11;617(2):205-11. Pubmed: 8408385 Link_out
    5. Gostner A, Blaut M, Schaffer V, Kozianowski G, Theis S, Klingeberg M, Dombrowski Y, Martin D, Ehrhardt S, Taras D, Schwiertz A, Kleessen B, Luhrs H, Schauber J, Dorbath D, Menzel T, Scheppach W: Effect of isomalt consumption on faecal microflora and colonic metabolism in healthy volunteers. Br J Nutr. 2006 Jan;95(1):40-50. Pubmed: 16441915 Link_out
    6. Ogata N, Shibata T: Binding of alkyl- and alkoxy-substituted simple phenolic compounds to human serum proteins. Res Commun Mol Pathol Pharmacol. 2000;107(1-2):167-73. Pubmed: 11334365 Link_out
    7. Letelier ME, Rodriguez E, Wallace A, Lorca M, Repetto Y, Morello A, Aldunate J: Trypanosoma cruzi: a possible control of transfusion-induced Chagas' disease by phenolic antioxidants. Exp Parasitol. 1990 Nov;71(4):357-63. Pubmed: 2121515 Link_out
    8. Geyer H, Scheunert I, Korte F: Bioconcentration potential of organic environmental chemicals in humans. Regul Toxicol Pharmacol. 1986 Dec;6(4):313-47. Pubmed: 3101145 Link_out
    9. Nishiyama T, Ohnishi J, Hashiguchi Y: Fused heterocyclic antioxidants: antioxidative activities of hydrocoumarins in a homogeneous solution. Biosci Biotechnol Biochem. 2001 May;65(5):1127-33. Pubmed: 11440127 Link_out
    10. Dills RL, Bellamy GM, Kalman DA: Quantitation of o-, m- and p-cresol and deuterated analogs in human urine by gas chromatography with electron capture detection. J Chromatogr B Biomed Sci Appl. 1997 Dec 5;703(1-2):105-13. Pubmed: 9448067 Link_out
    11. Bammens B, Verbeke K, Vanrenterghem Y, Evenepoel P: Evidence for impaired assimilation of protein in chronic renal failure. Kidney Int. 2003 Dec;64(6):2196-203. Pubmed: 14633143 Link_out
    12. Vanholder R, De Smet R, Lesaffer G: p-cresol: a toxin revealing many neglected but relevant aspects of uraemic toxicity. Nephrol Dial Transplant. 1999 Dec;14(12):2813-5. Pubmed: 10570076 Link_out
    13. Brunet P, Dou L, Cerini C, Berland Y: Protein-bound uremic retention solutes. Adv Ren Replace Ther. 2003 Oct;10(4):310-20. Pubmed: 14681860 Link_out