Human Metabolome Database Version 3.5

Showing metabocard for 4-Hydroxyphenylpyruvic acid (HMDB00707)

Record Information
Version 3.5
Creation Date 2005-11-16 08:48:42 -0700
Update Date 2013-05-29 13:28:36 -0600
HMDB ID HMDB00707
Secondary Accession Numbers None
Metabolite Identification
Common Name 4-Hydroxyphenylpyruvic acid
Description 4-Hydroxyphenylpyruvic acid (4-HPPA) is a keto acid that is involved in the tyrosine catabolism pathway. It is a product of the enzyme (R)-4-hydroxyphenyllactate dehydrogenase [EC 1.1.1.222] and is formed during tyrosine metabolism. The conversion from tyrosine to 4-HPPA is catalyzed by tyrosine aminotransferase. Additionally, 4-HPPA can be converted to homogentisic acid which is one of the precursors to ochronotic pigment. The enzyme 4-hydroxyphenylpyruvic acid dioxygenase (HPD) catalyzes the reaction that converts 4-hydroxyphenylpyruvic acid to homogentisic acid. A deficiency in the catalytic activity of HPD is known to lead to tyrosinemia type III, an autosomal recessive disorder characterized by elevated levels of blood tyrosine and massive excretion of tyrosine derivatives into urine. It has been shown that hawkinsinuria, an autosomal dominant disorder characterized by the excretion of 'hawkinsin,' may also be a result of HPD deficiency (PMID: 11073718 Link_out). There are two isomers of HPPA, specifically 4HPPA and 3HPPA, of which 4HPPA is the most common.
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. (p-hydroxyphenyl)-Pyruvate
  2. (p-hydroxyphenyl)-Pyruvic acid
  3. (p-Hydroxyphenyl)pyruvate
  4. (p-Hydroxyphenyl)pyruvic acid
  5. 3-(4-Hydroxyphenyl)-2-oxo-propanoate
  6. 3-(4-Hydroxyphenyl)-2-oxo-propanoic acid
  7. 3-(4-Hydroxyphenyl)-2-oxopropionate
  8. 3-(4-Hydroxyphenyl)-2-oxopropionic acid
  9. 3-(4-Hydroxyphenyl)pyruvate
  10. 3-(4-Hydroxyphenyl)pyruvic acid
  11. 3-(p-Hydroxyphenyl)-2-oxopropionate
  12. 3-(p-Hydroxyphenyl)-2-oxopropionic acid
  13. 3-(p-Hydroxyphenyl)pyruvate
  14. 3-(p-Hydroxyphenyl)pyruvic acid
  15. 4-Hydroxy-a-oxobenzenepropanoate
  16. 4-Hydroxy-a-oxobenzenepropanoic acid
  17. 4-Hydroxy-alpha-oxobenzenepropanoate
  18. 4-Hydroxy-alpha-oxobenzenepropanoic acid
  19. 4-Hydroxyphenylpyruvate
  20. 4HPPA
  21. HPPA
  22. Hydroxyphenylpyruvate
  23. Hydroxyphenylpyruvic acid
  24. p-Hydroxyphenylpyruvic
  25. Testacid
Chemical Formula C9H8O4
Average Molecular Weight 180.1574
Monoisotopic Molecular Weight 180.042258744
IUPAC Name 3-(4-hydroxyphenyl)-2-oxopropanoic acid
Traditional IUPAC Name 3-(4-hydroxyphenyl)-2-oxopropanoic acid
CAS Registry Number 156-39-8
SMILES OC(=O)C(=O)CC1=CC=C(O)C=C1
InChI Identifier InChI=1S/C9H8O4/c10-7-3-1-6(2-4-7)5-8(11)9(12)13/h1-4,10H,5H2,(H,12,13)
InChI Key KKADPXVIOXHVKN-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Aromatic Homomonocyclic Compounds
Class Benzyl Alcohols and Derivatives
Sub Class Phenylpyruvic Acid Derivatives
Other Descriptors
  • Organic Compounds
  • oxo carboxylic acid(ChEBI)
Substituents
  • Alpha Keto Acid
  • Carboxylic Acid
  • Ketone
  • Phenol
  • Phenol Derivative
Direct Parent Phenylpyruvic Acid Derivatives
Ontology
Status Detected and Quantified
Origin
  • Endogenous
  • Microbial
Biofunction Not Available
Application Not Available
Cellular locations
  • Cytoplasm
  • Mitochondria
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 219 - 220 °C Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 1.49 g/L ALOGPS
LogP 1.12 ALOGPS
LogP 1.6 ChemAxon
LogS -2.08 ALOGPS
pKa (strongest acidic) 2.91 ChemAxon
pKa (strongest basic) -6 ChemAxon
Hydrogen Acceptor Count 4 ChemAxon
Hydrogen Donor Count 2 ChemAxon
Polar Surface Area 74.6 A2 ChemAxon
Rotatable Bond Count 3 ChemAxon
Refractivity 44.69 ChemAxon
Polarizability 16.75 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 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 LC-ESI-QQ (API3000, Applied Biosystems) 10
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 20
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 30
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 40
MS/MS Spectrum LC-ESI-QQ (API3000, Applied Biosystems) 50
MS/MS Spectrum GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies )
MS/MS Spectrum GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)
MS/MS Spectrum GC-MS
MS/MS Spectrum GC-MS
MS/MS Spectrum GC-MS
MS/MS Spectrum GC-MS
[1H,1H] 2D NMR Spectrum
[1H,13C] 2D NMR Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Mitochondria
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Prostate
Pathways
Name SMPDB Link KEGG Link
Tyrosine Metabolism SMP00006 map00350 Link_out
Phenylalanine and Tyrosine Metabolism SMP00008 map00360 Link_out
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.37 +/- 0.23 uM Adult (>18 years old) Both Normal
Urine Detected and Quantified
1.65 (0.15-8.74) umol/mmol creatinine Adult (>18 years old) Male Normal
Urine Detected and Quantified
0.66 (0.23-2.50) umol/mmol creatinine Adult (>18 years old) Female Normal
Urine Detected and Quantified
4.9 (4.9-4.9) umol/mmol creatinine Infant (0-1 year old) Both Normal
Urine Detected and Quantified
4.6 (0.1-21.3) umol/mmol creatinine Newborn (0-30 days old) Both Normal
Urine Detected and Quantified
1.8 (0.1-4.5) umol/mmol creatinine Children (1-13 year old) Both Comment Normal
Urine Detected and Quantified
1.5 (0.6-3.4) umol/mmol creatinine Children (1-13 year old) Both Comment Normal
Urine Detected and Quantified
1.8 (1.2-4.3) umol/mmol creatinine Adolescent (13-18 years old) Both Comment Normal
Urine Detected and Quantified
1.00 (0.00-2.00) umol/mmol creatinine Adult (>18 years old) Both Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Urine Detected and Quantified 885.00 (170.00-1600.00) umol/mmol creatinine Children (1-13 year old) Both Hawkinsinuria
Urine Detected and Quantified 24.00 +/- 30.5 umol/mmol creatinine Newborn (0-30 days old) Both Phenylketonuria
Associated Disorders and Diseases
Disease References
Hawkinsinuria
      Phenylketonuria
      • Monch E, Kneer J, Jakobs C, Arnold M, Diehl H, Batzler U: Examination of urine metabolites in the newborn period and during protein loading tests at 6 months of age--Part 1. Eur J Pediatr. 1990;149 Suppl 1:S17-24. Pubmed: 2091926 Link_out
          Associated OMIM IDs
          DrugBank ID Not Available
          DrugBank Metabolite ID Not Available
          Phenol Explorer Compound ID Not Available
          Phenol Explorer Metabolite ID Not Available
          FoodDB ID FDB022193
          KNApSAcK ID Not Available
          Chemspider ID 954 Link_out
          KEGG Compound ID C01179 Link_out
          BioCyc ID P-HYDROXY-PHENYLPYRUVATE Link_out
          BiGG ID 37006 Link_out
          Wikipedia Link Hydroxyphenylpyruvic acid Link_out
          NuGOwiki Link HMDB00707 Link_out
          Metagene Link HMDB00707 Link_out
          METLIN ID 5675 Link_out
          PubChem Compound 979 Link_out
          PDB ID ENO Link_out
          ChEBI ID 15999 Link_out
          References
          Synthesis Reference Billek, Gerhard. p-Hydroxyphenylpyruvic acid. Organic Syntheses (1963), 43 49-54.
          Material Safety Data Sheet (MSDS) Download (PDF)
          General References
          1. Shoda J, Tanaka N, Osuga T, Matsuura K, Miyazaki H: Altered bile acid metabolism in liver disease: concurrent occurrence of C-1 and C-6 hydroxylated bile acid metabolites and their preferential excretion into urine. J Lipid Res. 1990 Feb;31(2):249-59. Pubmed: 2324645 Link_out
          2. Wolff JA, Barshop B, Nyhan WL, Leslie J, Seegmiller JE, Gruber H, Garst M, Winter S, Michals K, Matalon R: Effects of ascorbic acid in alkaptonuria: alterations in benzoquinone acetic acid and an ontogenic effect in infancy. Pediatr Res. 1989 Aug;26(2):140-4. Pubmed: 2771520 Link_out
          3. Deutsch JC: Determination of p-hydroxyphenylpyruvate, p-hydroxyphenyllactate and tyrosine in normal human plasma by gas chromatography-mass spectrometry isotope-dilution assay. J Chromatogr B Biomed Sci Appl. 1997 Mar 7;690(1-2):1-6. Pubmed: 9106023 Link_out
          4. Guneral F, Bachmann C: Age-related reference values for urinary organic acids in a healthy Turkish pediatric population. Clin Chem. 1994 Jun;40(6):862-6. Pubmed: 8087979 Link_out
          5. Muskiet FA, Fremouw-Ottevangers DC, Nagel GT, Wolthers BG, de Vries JA: Determination of 3-methoxy-4-hydroxyphenylpyruvic acid, 3,4-dihydroxyphenylethylene glycol, and 3,4-dihydroxyphenylmandelic acid in urine by mass fragmentography, with use of deuterium-labeled internal standards. Clin Chem. 1978 Nov;24(11):2001-8. Pubmed: 709835 Link_out
          6. Endo F, Katoh H, Yamamoto S, Matsuda I: A murine model for type III tyrosinemia: lack of immunologically detectable 4-hydroxyphenylpyruvic acid dioxygenase enzyme protein in a novel mouse strain with hypertyrosinemia. Am J Hum Genet. 1991 Apr;48(4):704-9. Pubmed: 2014797 Link_out
          7. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411 Link_out
          8. Tomoeda K, Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F: Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria. Mol Genet Metab. 2000 Nov;71(3):506-10. Pubmed: 11073718 Link_out

          Enzymes
          Name: Macrophage migration inhibitory factor
          Reactions:
          4-Hydroxyphenylpyruvic acid unknown 2-Hydroxy-3-(4-hydroxyphenyl)propenoic acid details
          Gene Name: MIF
          Uniprot ID: P14174 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Tyrosine aminotransferase
          Reactions:
          L-Tyrosine + Oxoglutaric acid unknown 4-Hydroxyphenylpyruvic acid + L-Glutamic acid details
          Gene Name: TAT
          Uniprot ID: P17735 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Aspartate aminotransferase, cytoplasmic
          Reactions:
          L-Tyrosine + Oxoglutaric acid unknown 4-Hydroxyphenylpyruvic acid + L-Glutamic acid details
          Gene Name: GOT1
          Uniprot ID: P17174 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: Aspartate aminotransferase, mitochondrial
          Reactions:
          L-Tyrosine + Oxoglutaric acid unknown 4-Hydroxyphenylpyruvic acid + L-Glutamic acid details
          Gene Name: GOT2
          Uniprot ID: P00505 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: 4-hydroxyphenylpyruvate dioxygenase
          Reactions:
          4-Hydroxyphenylpyruvic acid + Oxygen unknown Homogentisic acid + CO(2) details
          4-Hydroxyphenylpyruvic acid + Oxygen unknown Homogentisic acid + Carbon dioxide details
          Gene Name: HPD
          Uniprot ID: P32754 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA
          Name: L-amino-acid oxidase
          Reactions:
          L-Tyrosine + Water + Oxygen unknown 4-Hydroxyphenylpyruvic acid + Ammonia + Hydrogen peroxide details
          Gene Name: IL4I1
          Uniprot ID: Q96RQ9 Link_out
          Protein Sequence: FASTA
          Gene Sequence: FASTA