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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2013-05-29 19:28:36 UTC
HMDB IDHMDB00707
Secondary Accession NumbersNone
Metabolite Identification
Common Name4-Hydroxyphenylpyruvic acid
Description4-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 ). There are two isomers of HPPA, specifically 4HPPA and 3HPPA, of which 4HPPA is the most common.
Structure
Thumb
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 FormulaC9H8O4
Average Molecular Weight180.1574
Monoisotopic Molecular Weight180.042258744
IUPAC Name3-(4-hydroxyphenyl)-2-oxopropanoic acid
Traditional Name3-(4-hydroxyphenyl)-2-oxopropanoic acid
CAS Registry Number156-39-8
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 KeyKKADPXVIOXHVKN-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Homomonocyclic Compounds
ClassBenzyl Alcohols and Derivatives
Sub ClassPhenylpyruvic Acid Derivatives
Other Descriptors
  • Organic Compounds
  • oxo carboxylic acid(ChEBI)
Substituents
  • Alpha Keto Acid
  • Carboxylic Acid
  • Ketone
  • Phenol
  • Phenol Derivative
Direct ParentPhenylpyruvic Acid Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Microbial
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Cytoplasm
  • Mitochondria
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point219 - 220 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility1.49 g/LALOGPS
logP1.12ALOGPS
logP1.6ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)2.91ChemAxon
pKa (Strongest Basic)-6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity44.69ChemAxon
Polarizability16.75ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Cytoplasm
  • Mitochondria
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
Phenylalanine and Tyrosine MetabolismSMP00008map00360
Tyrosine MetabolismSMP00006map00350
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.37 +/- 0.23 uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified1.65 (0.15-8.74) umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified0.66 (0.23-2.50) umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified4.9 (4.9-4.9) umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified4.6 (0.1-21.3) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified1.8 (0.1-4.5) umol/mmol creatinineChildren (1-13 years old)Both
Normal
details
UrineDetected and Quantified1.5 (0.6-3.4) umol/mmol creatinineChildren (1-13 years old)Both
Normal
details
UrineDetected and Quantified1.8 (1.2-4.3) umol/mmol creatinineAdolescent (13-18 years old)Both
Normal
details
UrineDetected and Quantified1.00 (0.00-2.00) umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
UrineDetected and Quantified885.00 (170.00-1600.00) umol/mmol creatinineChildren (1-13 years old)BothHawkinsinuria details
UrineDetected and Quantified24.00 +/- 30.5 umol/mmol creatinineNewborn (0-30 days old)BothPhenylketonuria details
Associated Disorders and Diseases
Disease References
Hawkinsinuria
  1. MetaGene
Phenylketonuria
  1. 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
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022193
KNApSAcK IDNot Available
Chemspider ID954
KEGG Compound IDC01179
BioCyc IDP-HYDROXY-PHENYLPYRUVATE
BiGG ID37006
Wikipedia LinkHydroxyphenylpyruvic acid
NuGOwiki LinkHMDB00707
Metagene LinkHMDB00707
METLIN ID5675
PubChem Compound979
PDB IDENO
ChEBI ID15999
References
Synthesis ReferenceBillek, Gerhard. p-Hydroxyphenylpyruvic acid. Organic Syntheses (1963), 43 49-54.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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

Enzymes

General function:
Involved in cell surface binding
Specific function:
Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.
Gene Name:
MIF
Uniprot ID:
P14174
Molecular weight:
12476.19
Reactions
4-Hydroxyphenylpyruvic acid → 2-Hydroxy-3-(4-hydroxyphenyl)propenoic aciddetails
General function:
Involved in 1-aminocyclopropane-1-carboxylate synthase activity
Specific function:
Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine.
Gene Name:
TAT
Uniprot ID:
P17735
Molecular weight:
50398.895
Reactions
L-Tyrosine + Oxoglutaric acid → 4-Hydroxyphenylpyruvic acid + L-Glutamic aciddetails
General function:
Involved in transferase activity, transferring nitrogenous groups
Specific function:
Plays a key role in amino acid metabolism (By similarity).
Gene Name:
GOT1
Uniprot ID:
P17174
Molecular weight:
46247.14
Reactions
L-Tyrosine + Oxoglutaric acid → 4-Hydroxyphenylpyruvic acid + L-Glutamic aciddetails
General function:
Involved in transferase activity, transferring nitrogenous groups
Specific function:
Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Plays a key role in amino acid metabolism. Important for metabolite exchange between mitochondria and cytosol. Facilitates cellular uptake of long-chain free fatty acids.
Gene Name:
GOT2
Uniprot ID:
P00505
Molecular weight:
47517.285
Reactions
L-Tyrosine + Oxoglutaric acid → 4-Hydroxyphenylpyruvic acid + L-Glutamic aciddetails
General function:
Involved in 4-hydroxyphenylpyruvate dioxygenase activity
Specific function:
Key enzyme in the degradation of tyrosine.
Gene Name:
HPD
Uniprot ID:
P32754
Molecular weight:
40497.105
Reactions
4-Hydroxyphenylpyruvic acid + Oxygen → Homogentisic acid + CO(2)details
4-Hydroxyphenylpyruvic acid + Oxygen → Homogentisic acid + Carbon dioxidedetails
General function:
Involved in oxidoreductase activity
Specific function:
Lysosomal L-amino-acid oxidase with highest specific activity with phenylalanine. May play a role in lysosomal antigen processing and presentation (By similarity).
Gene Name:
IL4I1
Uniprot ID:
Q96RQ9
Molecular weight:
65327.26
Reactions
L-Tyrosine + Water + Oxygen → 4-Hydroxyphenylpyruvic acid + Ammonia + Hydrogen peroxidedetails