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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2016-02-11 01:03:15 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
ValueSource
(P-Hydroxyphenyl)pyruvic acidChEBI
3-(4-HYDROXY-phenyl)pyruvIC ACIDChEBI
3-(4-Hydroxyphenyl)pyruvic acidChEBI
3-(P-Hydroxyphenyl)-2-oxopropanoic acidChEBI
4-Hydroxy alpha-oxobenzenepropanoic acidChEBI
4-Hydroxyphenylpyruvic acidChEBI
P-Hydroxyphenylpyruvic acidChEBI
(P-Hydroxyphenyl)pyruvateGenerator
(4-Hydroxyphenyl)pyruvateGenerator
3-(4-HYDROXY-phenyl)pyruvateGenerator
3-(4-Hydroxyphenyl)pyruvateGenerator
3-(P-Hydroxyphenyl)-2-oxopropanoateGenerator
4-Hydroxy a-oxobenzenepropanoateGenerator
4-Hydroxy a-oxobenzenepropanoic acidGenerator
4-Hydroxy alpha-oxobenzenepropanoateGenerator
4-Hydroxy α-oxobenzenepropanoateGenerator
4-Hydroxy α-oxobenzenepropanoic acidGenerator
4-HydroxyphenylpyruvateGenerator
P-HydroxyphenylpyruvateGenerator
(P-Hydroxyphenyl)-pyruvateHMDB
(P-Hydroxyphenyl)-pyruvic acidHMDB
3-(4-Hydroxyphenyl)-2-oxo-propanoateHMDB
3-(4-Hydroxyphenyl)-2-oxo-propanoic acidHMDB
3-(4-Hydroxyphenyl)-2-oxopropionateHMDB
3-(4-Hydroxyphenyl)-2-oxopropionic acidHMDB
3-(P-Hydroxyphenyl)-2-oxopropionateHMDB
3-(P-Hydroxyphenyl)-2-oxopropionic acidHMDB
3-(P-Hydroxyphenyl)pyruvateHMDB
3-(P-Hydroxyphenyl)pyruvic acidHMDB
4-Hydroxy-a-oxobenzenepropanoateHMDB
4-Hydroxy-a-oxobenzenepropanoic acidHMDB
4-Hydroxy-alpha-oxobenzenepropanoateHMDB
4-Hydroxy-alpha-oxobenzenepropanoic acidHMDB
4HPPAHMDB
HPPAHMDB
HydroxyphenylpyruvateHMDB
Hydroxyphenylpyruvic acidHMDB
P-HydroxyphenylpyruvicHMDB
TestacidHMDB
Chemical FormulaC9H8O4
Average Molecular Weight180.1574
Monoisotopic Molecular Weight180.042258744
IUPAC Name3-(4-hydroxyphenyl)-2-oxopropanoic acid
Traditional Name4-hydroxyphenylpyruvic 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 KeyInChIKey=KKADPXVIOXHVKN-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpyruvic acid derivatives. These are compounds containing a phenylpyruvic acid moiety, which consists of a phenyl group substituted at the second position by an pyruvic acid.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylpyruvic acid derivatives
Direct ParentPhenylpyruvic acid derivatives
Alternative Parents
Substituents
  • Phenylpyruvate
  • 3-phenylpropanoic-acid
  • Phenol
  • Keto acid
  • Alpha-keto acid
  • Alpha-hydroxy ketone
  • Ketone
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
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 mg/mLALOGPS
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 Area74.6 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity44.69 m3·mol-1ChemAxon
Polarizability16.75 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-002f-1920000000-75b07d9c09371340939fView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-00xr-9340000000-087aad2497b3493d27c0View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 2 TMS)splash10-002o-5910000000-fd1e55c84c79bfeca559View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 2 TMS)splash10-002f-1941000000-2b4c87544657895fcaf6View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 3 TMS)splash10-014i-3492100000-483bdcea11d60fe4d306View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 3 TMS)splash10-014i-6791000000-ddc0a3b695cd1d0769f2View in MoNA
GC-MSGC-MS Spectrum - GC-MSNot Available
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)splash10-0a4i-0900000000-12033042c41b550bed42View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)splash10-0a4i-0900000000-6e8a3701c6d254cc824dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)splash10-0560-1900000000-8082c68e259d24234d05View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-004i-0900000000-2416d7f64101b9473cbbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-0a4i-2900000000-b4c21b3d9751b9e56d67View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0005-9400000000-708e258e692a0abfbc92View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0002-9100000000-7d75e23ae6944c1e9c6dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-001m-9000000000-fb80dcbab23323a042afView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-08gr-0900000000-be3cb913118057f499d1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-06rj-0900000000-6bebea0fda2ef3a2263bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a6r-6900000000-ede11b81a97e891c66e3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0900000000-2584f872c980915c1739View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01s9-1900000000-249c71cfa9cefe2a8020View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001l-3900000000-66991d861a91be9b9286View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0a59-5900000000-6c003e26816579df31caView in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,1H] 2D NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Mitochondria
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Prostate
Pathways
NameSMPDB LinkKEGG Link
AlkaptonuriaSMP00169Not Available
Disulfiram PathwaySMP00429Not Available
Dopamine beta-hydroxylase deficiencySMP00498Not Available
HawkinsinuriaSMP00190Not Available
Monoamine oxidase-a deficiency (MAO-A)SMP00533Not Available
Phenylalanine and Tyrosine MetabolismSMP00008map00360
PhenylketonuriaSMP00206Not Available
Tyrosine MetabolismSMP00006map00350
Tyrosinemia Type 2 (or Richner-Hanhart syndrome)SMP00369Not Available
Tyrosinemia Type 3 (TYRO3)SMP00370Not Available
Tyrosinemia Type ISMP00218Not Available
Tyrosinemia, transient, of the newbornSMP00494Not Available
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
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
UrineDetected and Quantified1.00 (0.00-2.00) umol/mmol creatinineAdult (>18 years old)BothHawkinsinuria details
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 [Link]
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. [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. [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. [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. [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. [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. [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. [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. [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. [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