Disease relevance of phenylpyruvate

• Phenylpyruvate, fetal damage, and maternal phenylketonuria syndrome [1].
• Phenylketonuria: metabolic alterations induced by phenylalanine and phenylpyruvate [2].
• Species of coryneform bacteria (Corynebacterium glutamicum, Brevibacterium flavum, and B. ammoniagenes) are capable of transaminating all three of the aromatic pathway intermediates; prephenate, phenylpyruvate, and 4-hydroxy-phenylpyruvate [3].
• Dual biosynthetic pathways diverge from prephenate to L-phenylalanine in Erwinia herbicola, the unique intermediates of these pathways being phenylpyruvate and L-arogenate [4].
• Xenofuranones A and B: phenylpyruvate dimers from Xenorhabdus szentirmaii [5].

High impact information on phenylpyruvate

• However, the failure of phenylpyruvate to substitute for Phe in this interaction suggests that proteolytic inhibition by phenylpyruvate and Phe is mediated through similar, although independent, plasma membrane sites [6].
• Each aminotransferase is capable of transamination in vitro with any of the three keto acid intermediates in the aromatic pathway (phenylpyruvate, 4-hydroxyphenylpyruvate, or prephenate) [7].
• The former is about one-third as efficient as the best malate dehydrogenase selected, whilst the latter had about one-seventh of the best phenylpyruvate dehydrogenase activity [8].
• The metabolites of phenylalanine, phenylacetate, phenyllactate, phenylpyruvate and phenylethylamine, were measured in the urine of PKU patients [9].
• Macrophage migration inhibitory factor (MIF) exhibits tautomerase activity on phenylpyruvate and has E-stereochemistry preference [10].

Chemical compound and disease context of phenylpyruvate

• The 1700:1 selectivity of enzyme BL1 for phenylpyruvate over pyruvate is that required in a phenyllactate dehydrogenase to be used in monitoring phenylpyruvate in the urine of patients with phenylketonuria consuming an apparently phenylalanine-free diet [11].
• Previous kinetic studies of Streptomyces avermitilis HPPD have shown that the substrate analog phenylpyruvate (PPA), which only differs from the normal substrate (4-hydroxyphenyl)pyruvate (HPP) by the absence of a para-hydroxyl group on the aromatic ring, does not induce a reaction with dioxygen [12].
• The enzyme purified to homogeneity from recombinant E. coli catalyzed the NADPH-dependent formation of N-alkyl-L-amino acids from the corresponding alpha-oxo acids (e.g. pyruvate, phenylpyruvate, and hydroxypyruvate) and alkylamines (e.g. methylamine, ethylamine, and propylamine) [13].

Biological context of phenylpyruvate

• Steady-state kinetic investigations of the reactions with chorismate or prephenate as substrate and studies of the overall conversion of chorismate to phenylpyruvate indicate that there are two distinct active sites [14].
• Both mutants remain capable of inhibiting monocyte chemotaxis and random migration despite significantly reduced or no phenylpyruvate tautomerase activity [15].
• A50 concentrations of clofibric acid and phenylpyruvate also increased flux (decarboxylation of alpha-keto[1-14C]isovalerate) through branched-chain alpha-ketoacid dehydrogenase in perfused rat heart [16].
• An oxidoreductase with an extremely broad substrate specificity reducing reversibly 2-oxocarboxylates at the expense of reduced artificial redox mediators to (2R)-hydroxycarboxylates has been purified to a specific activity of up to 1800 mumol.min-1.mg-1 for the reduction of phenylpyruvate [17].
• The main objective of the present study with rat blood serum was to evaluate the possibility of changes in nucleotide hydrolysis by phenylalanine (Phe) and phenylpyruvate (PP), the levels of which could increase in the circulation of individuals with phenylketonuria [18].

Anatomical context of phenylpyruvate

• Hence, the effect of phenylpyruvate was not initiated within the cell but more likely from the plasma membrane [6].
• Inhibition of acetoacetate oxidation by brain mitochondria from the suckling rat by phenylpyruvate and alpha ketoisocaproate [19].
• Both phenylpyruvate oxidase and phenylpyruvate decarboxylase activities could be demonstrated in the cell-free system [20].
• The main objective of the present study was to characterize the inhibition by phenylalanine and phenylpyruvate of ATP diphosphohydrolase activity in synaptosomes from the brain cortex of rats [21].
• The PKU fibroblasts, unlike normal ones, were found to excrete into the culture medium phenylpyruvate, 4-hydroxyphenylpyruvate, indolyl-3-acetate and an unidentified metabolite containing the phenyl group [22].

Associations of phenylpyruvate with other chemical compounds

• The binding of HPP, phenylpyruvate (PPA), and pyruvate to the holoenzyme produces a weak ligand charge-transfer band at approximately 500 nm that is indicative of bidentate binding of the 1-carboxylate and 2-keto pyruvate oxygen atoms to the active site metal ion [23].
• The catalytic specificity of recombinant TsMIF in the ketonization of phenylpyruvate (1.4x10(6) M(-1) x s(-1)) was comparable with that of human MIF, while that of p-hydroxyphenylpyruvate (9.1x10(4) M(-1) x s(-1)) was 71-fold lower [24].
• 4. Phenylpyruvate inhibited with respect to acetoacetyl-CoA both the mitochondrial (Ki equals 3.2 mM) and cytoplasmic (Ki equals 5.2 mM) acetoacetyl-CoA thiolase activities [25].
• Analyses of phenylalanine catabolite production and phenylpyruvate decarboxylase enzyme assays indicated that ARO10 was sufficient to encode phenylpyruvate decarboxylase activity in the absence of the four other candidate genes [26].
• In the presence of 2-ketoglutarate, phenylpyruvate formation is measured at 320 nm at basic pH [27].

Gene context of phenylpyruvate

• The K(m) and V(max) values of the two activities differed, showing that Aro10p is the physiologically relevant phenylpyruvate decarboxylase in wild-type cells [26].
• Mechanism of the phenylpyruvate tautomerase activity of macrophage migration inhibitory factor: properties of the P1G, P1A, Y95F, and N97A mutants [28].
• Although a detailed understanding of the biological functions of MIF has not yet been found, it is known that MIF catalyzes the tautomerization of phenylpyruvate and a non-physiological molecule, D-dopachrome [29].
• Recently, it has been reported that MIF has D-dopachrome tautomerase, phenylpyruvate tautomerase and thiol protein oxidoreductase activities, although the physiological significance of those activities is not yet clear [30].
• Phenylpyruvate was the most effective inhibitor, reducing activity to 0.2% of control values in the extract, and 11% of control values for purified MPST when added to the reaction at 30 mM [31].

Analytical, diagnostic and therapeutic context of phenylpyruvate

• High-performance liquid chromatography assays of phenylpyruvate and phenylpyruvate oxidase [32].

References