4-Hydroxyphenylpyruvic Acid

• CAT Number: R031902
• CAS Number: 156-39-8
• Molecular Formula: C9H8O4
• Molecular Weight: 180.159
• Purity: ≥95%
• Storage: Store at RT
• IUPAC Name: 3-(4-hydroxyphenyl)-2-oxopropanoic acid
• InChI: InChI=1S/C9H8O4/c10-7-3-1-6(2-4-7)5-8(11)9(12)13/h1-4,10H,5H2,(H,12,13)
• InChIKey: KKADPXVIOXHVKN-UHFFFAOYSA-N
• SMILES: C1=CC(=CC=C1CC(=O)C(=O)O)O

4-Hydroxyphenylpyruvic acid (4-HPPA)(CAS: 156-39-8) is an intermediate in the metabolism of the amino acid phenylalanine. The aromatic side chain of phenylalanine is hydroxylated by the enzyme phenylalanine hydroxylase to form tyrosine. The conversion from tyrosine to 4-HPPA is in turn catalyzed by tyrosine aminotransferase. Additionally, 4-HPPA can be converted to homogentisic acid which is one of the precursors to ochronotic pigment.

Reference

[1]. Nature. 1960 May 14;186:529-31. doi: 10.1038/186529a0.
Alkaline conversion of 4-hydroxyphenylpyruvic acid to 4-hydroxybenzaldehyde.
DOY CH.
DOI: 10.1038/186529a0 PMID: 13817925 [Indexed for MEDLINE]

[2]. J Biol Chem. 1992 Dec 5;267(34):24235-40.
Primary structure deduced from complementary DNA sequence and expression in cultured cells of mammalian 4-hydroxyphenylpyruvic acid dioxygenase. Evidence that the enzyme is a homodimer of identical subunits homologous to rat liver-specific alloantigen F.
Endo F(1), Awata H, Tanoue A, Ishiguro M, Eda Y, Titani K, Matsuda I.
Author information: (1)Department of Pediatrics, Kumamoto University Medical School, Japan.
4-Hydroxyphenylpyruvic acid dioxygenase is an important enzyme in tyrosine catabolism in most organisms. From porcine and human liver cDNA libraries we isolated complementary DNA inserts for the enzyme. Protein sequence analysis of the porcine enzyme revealed a block of the amino terminus of the mature enzyme. Comparison of the amino acid sequence determined by Edman degradation of peptides derived from porcine liver 4-hydroxyphenylpyruvic acid dioxygenase with the nucleotide sequences revealed the primary structure of the porcine and human enzymes. The mature human and porcine enzymes have an 89% amino acid sequence identity in amino acid residues and are composed of 392 amino acid residues. A computer-assisted homology search revealed that the enzyme is 88% identical in amino acid sequence to rat liver-specific alloantigen F. A monoclonal antibody (mob 51), which can immunoprecipitate both the human and porcine enzymes, was developed. Cultured BMT-10 cells transfected with the cDNA insert of the human enzyme, using the expression vector pCAGGSneodE, produced a polypeptide with an M(r) of 43,000, which was immunoprecipitated with mob 51. Enzymic activity of the enzyme was detected in the transfected cells but not in the mock transfected cells. These findings suggest that the human 4-hydroxyphenylpyruvic acid dioxygenase is a homodimer of two identical subunits with an M(r) of 43,000. Liver-specific alloantigen F seems to be closely related to the enzyme or possibly to the subunit of the enzyme itself. Elucidation of the complete amino acid sequence of the enzyme is expected to reveal structure-function relationships of this metabolically important enzyme and to shed light on inherited disorders related to tyrosine metabolism, especially tyrosinemia types 1 and 3.
PMID: 1339442 [Indexed for MEDLINE]

[3]. Mol Genet Metab. 2000 Nov;71(3):506-10. doi: 10.1006/mgme.2000.3085.
Mutations in the 4-hydroxyphenylpyruvic acid dioxygenase gene are responsible for tyrosinemia type III and hawkinsinuria.
Tomoeda K(1), Awata H, Matsuura T, Matsuda I, Ploechl E, Milovac T, Boneh A, Scott CR, Danks DM, Endo F.
Author information: (1)Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto, Japan.
The enzyme 4-hydroxyphenylpyruvic acid dioxygenase (HPD) catalyzes the reaction of 4-hydroxyphenylpyruvic acid to homogentisic acid in the tyrosine catabolism pathway. A deficiency in the catalytic activity of HPD may 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 postulated that hawkinsinuria, an autosomal dominant disorder characterized by the excretion of 'hawkinsin,' may also be a result of HPD deficiency. Hawkinsin is a sulfur amino acid identified as (2-l-cystein-S-yl, 4-dihydroxycyclohex-5-en-1-yl)acetic acid. Patients with hawkinsinuria excrete this metabolite in their urine throughout their life, although symptoms of metabolic acidosis and tyrosinemia improve in the first year of life. We performed analyses of the HPD gene in a patient with tyrosinemia type III and two unrelated patients with hawkinsinuria. A homozygous missense mutation predicting an Ala to Val change at codon 268 (A268V) in the HPD gene was found in the patient with tyrosinemia type III. A heterozygous missense mutation predicting an Ala to Thr change at codon 33 (A33T) was found in the same HPD gene in the two patients with hawkinsinuria. These findings support the hypothesis that alterations in the structure and activity of HPD are causally related to two different metabolic disorders, tyrosinemia type III and hawkinsinuria.
DOI: 10.1006/mgme.2000.3085 PMID: 11073718 [Indexed for MEDLINE]

[4]. Clin Chem. 1978 Nov;24(11):2001-8.
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.
Muskiet FA, Fremouw-Ottevangers DC, Nagel GT, Wolthers BG, de Vries JA.
We report the determination of 3-methoxy-4-hydroxyphenylpyruvic acid, 3,4-dihydroxyphenylmandelic acid, and 3,4-dihydroxyphenylethylene glycol in urine, by use of gas chromatography/mass spectrometry in combination with a simple purification method and deuterium-labeled internal standards. Normal excretion values in terms of creatinine, expressed as a function of age, are given, together with results obtained for patients with neuroblastoma, pheochromocytoma, or parkinsonism treated with L-DOPA + peripheral decarboxylase inhibitor, and for a patient receiving dopamine. We were unable to identify 3, 4-dihydroxyphenyllactic acid in urine. The results obtained and their relation to other catecholamine metabolites and catecholamine-precursor metabolites in urine are discussed.
PMID: 709835 [Indexed for MEDLINE]

[5]. Genomics. 1994 Oct;23(3):534-9. doi: 10.1006/geno.1994.1540.
Structure of the human 4-hydroxyphenylpyruvic acid dioxygenase gene (HPD).
Awata H(1), Endo F, Matsuda I.
Author information: (1)Department of Pediatrics, School of Medicine, Kumamoto University, Japan.
4-Hydroxyphenylpyruvic acid dioxygenase (HPD) is an important enzyme in tyrosine catabolism in most organisms. The activity of this enzyme is expressed mainly in the liver and developmentally regulated in mammals, and a genetic deficiency in this enzyme in humans and mice leads to hereditary tyrosinemia type 3. Using human HPD cDNA as a probe, a chromosomal gene related to HPD was isolated from human gene libraries. The human HPD gene is over 30 kb long and is split into 14 exons. The extract size and boundaries of exon blocks were determined, and all of the splice donor and acceptor sites conformed to the GT/AG rule. Analysis of the 5' flanking sequence of the gene suggests that expression of the gene is regulated by hepatocyte-specific and liver-enriched transcription factors, as well as by hormones. These features of the 5' flanking region of the gene are similar to those of other genes that are specifically expressed in hepatocytes and that are developmentally regulated.
DOI: 10.1006/geno.1994.1540 PMID: 7851880 [Indexed for MEDLINE]