Disease relevance of p-Hydroxyphenylpyruvic acid

• Purified preparations of 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. strain P [1].
• This cDNA encodes a functional p-hydroxyphenylpyruvate dioxygenase, as evidenced by expression studies with transformed Escherichia coli cells [2].
• Transient tyrosinemia, characterized by 5-10-fold increases over basal excretion of tyrosine, p-hydroxyphenyllactate, and p-hydroxyphenylpyruvate in urine, was noted in five of the infants [3].
• A Streptomyces avermitilis gene encoding a 4-hydroxyphenylpyruvic acid dioxygenase-like protein that directs the production of homogentisic acid and an ochronotic pigment in Escherichia coli [4].
• 2-(2-Nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) is a potent inhibitor of rat liver 4-hydroxyphenylpyruvate dioxygenase (HPPD) leading to tyrosinemia and corneal opacity [5].

High impact information on p-Hydroxyphenylpyruvic acid

• In biopsy samples of histologically normal livers, total tyrosine aminotransferase activity was 10.5 +/- 1.8 nmol p-hydroxyphenylpyruvate formed/mg of protein per min (mean +/- SEM; n = 10) whereas the corresponding figures for 7 cirrhotics were 4.95 +/- 0.85 [6].
• We find that p-hydroxyphenylpyruvate, a catalytic substrate of MIF, binds to the N-terminal region and interacts with Pro-1 [7].
• One aminotransferase exhibited a narrow range of substrate specificity, recognizing only the combination of L-glutamate with prephenate, phenylpyruvate, or 4-hydroxyphenylpyruvate [8].
• Tyrosine and the serotonin-precursor 5-hydroxytryptophan also activate AHR signaling in combination with aspartate aminotransferase, suggesting that 4-hydroxyphenylpyruvate and 5-hydroxyindolepyruvate also act as proagonists of AHR [9].
• 4-Hydroxyphenylpyruvate dioxygenase (4HPPD) catalyzes the formation of homogentisate (2,5-dihydroxyphenylacetate) from p-hydroxyphenylpyruvate and molecular oxygen [10].

Chemical compound and disease context of p-Hydroxyphenylpyruvic acid

• Pseudomonas putida metabolizes Phe and Tyr through a peripheral pathway involving hydroxylation of Phe to Tyr (PhhAB), conversion of Tyr into 4-hydroxyphenylpyruvate (TyrB), and formation of homogentisate (Hpd) as the central intermediate [11].
• Biologically, human 4-hydroxyphenylpyruvic acid dioxygenase, involved in tyrosinemia type 3, is predicted to be structurally and functionally related to the glyoxalase I family [12].
• In the present study, 2(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of p-hydroxyphenylpyruvate dioxygenase (which catalyzes the formation of homogentisic acid from p-hydroxyphenylpyruvic acid) was adopted as a possible therapeutic agent for alkaptonuria [13].
• Tritium isotope effects in the reaction catalyzed by 4-hydroxyphenylpyruvate dioxygenase from pseudomonas sp. strain P.J. 874 [14].
• Isotope-dilution assays are sensitive enough to determine tyrosine, p-hydroxyphenylpyruvate and p-hydroxyphenyllactate content in normal subjects, and may be useful for studying disorders of tyrosine metabolism, including inborn errors of metabolism, liver disease and ascorbic acid deficiencies [15].

Biological context of p-Hydroxyphenylpyruvic acid

• We also report the isolation and nucleotide sequence of a cDNA encoding a carrot p-hydroxyphenylpyruvate dioxygenase [2].
• The three binding sites for p-hydroxyphenylpyruvate in the MIF trimer lie at the interface between two subunits [16].
• An Fe2+/oxygen-dependent enzyme, it converts p-hydroxyphenylpyruvate into homogentisate and is part of the superfamily of alpha-ketoglutarate-dependent enzymes that couples oxidative decarboxylation of an alpha-ketoacid cofactor to oxidative modification of its substrate [17].
• Sequence analysis of the 1.5-kb DNA that caused pigment production revealed a single open reading frame encoding a protein of 41.6 kDa (380 amino acids) that resembled several prokaryotic and eukaryotic 4-hydroxyphenylpyruvate dioxygenases (HPDs) [4].
• The enzyme catalyzed the oxidative deamination of L-phenylalanine and several other L-amino acids and the reductive amination of phenylpyruvate and p-hydroxyphenylpyruvate [18].

Anatomical context of p-Hydroxyphenylpyruvic acid

• Our results provide evidence that, in cultured carrot cells, p-hydroxyphenylpyruvate dioxygenase is associated with the cytosol [2].
• Characterization of transplastomic tobacco plants with a plastid localized barley 4-hydroxyphenylpyruvate dioxygenase [19].
• The Tetrahymena homolog of bacterial and mammalian 4-hydroxyphenylpyruvate dioxygenases localizes to membranes of the endoplasmic reticulum [20].
• Total tyrosine aminotransferase activity in the supernatant fraction of adult human liver was 19.8 nmol of p-hydroxyphenylpyruvate formed per min/mg of protein as compared to 0.53 in fetuses of 12--22 weeks of gestational age and 2.0 in the newborn [21].

Associations of p-Hydroxyphenylpyruvic acid with other chemical compounds

• Pretyrosine is formed from prephenate via the activity of at least one species of aromatic aminotransferase which is significantly greater with prephenate as substrate than with either phenylpyruvate or 4-hydroxyphenylpyruvate [22].
• The enzyme p-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27) from both Zea mays seedlings and liver tissues, was found to be subject to strong inhibition by SC-0051 [23].
• The enzyme 4-hydroxyphenylpyruvic acid dioxygenase (HPD) catalyzes the reaction of 4-hydroxyphenylpyruvic acid to homogentisic acid in the tyrosine catabolism pathway [24].
• 4-(4-Hydroxyphenyl)-5-(4-hydroxyphenylmethyl)-2-hydroxyfurane-2-one 1 was prepared by an acidic dimerisation of 4-hydroxyphenylpyruvic acid and some of its antioxidant and spectroscopic properties have been measured and compared to that of ascorbic acid [25].
• The 4-hydroxyphenylpyruvate dioxygenase (HPD) is the only enzyme of the biosynthetic pathway of tocopherols and tocotrienols localized outside of plastids [19].

Gene context of p-Hydroxyphenylpyruvic acid

• HPD-deficient mice are a good model with which to examine the biological effects of 4-hydroxyphenylpyruvic acid, which is a keto acid that causes no apparent visceral damage [26].
• The protein encoded by the Shewanella colwelliana melA gene is a p-hydroxyphenylpyruvate dioxygenase [27].
• Inhibition of transketolase by p-hydroxyphenylpyruvate [28].
• Acute administration of Morphine (20 mg/kg/s.c.) in the rat results in a rise of liver tyrosine aminotransferase (TAT) expressed as mumoles of p-hydroxyphenylpyruvate/100 mg/h. With chronic administration, a tolerance develops to this enzymatic effect [29].
• 2) p-Hydroxyphenylpyruvate inhibits kynureninase activity [30].

References