Diminished phenylketonuria in phenylpyruvic oligophrenia after administration of L-glutamine, L-glutamate or L-asparagine.
Explore the source record for details and available documents.
Asparagine↗
SEARCH · Search PubMed
Results for “PHENYLPYRUVIC ACID”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
[Repression of the synthesis and allosteric inhibition of 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase in facultative methylotrophic bacterium Pseudomonas sp. M].
The synthesis of 3-deoxy-D-arabinoheptulosonate-7-phosphate-synthase has been shown to be repressed by tyrosine and phenylalanine in the cells of facultative methylotrophic bacteria Pseudomonas sp. M. Activity of the enzyme is subjected to allosteric inhibition by tyrosine, tryptophane, anthranylate and phenylpyruvate.
3-Deoxy-7-Phosphoheptulonate Synthase↗
Some fluorescent properties of non-enzymic transamination and measurement of the relative molecular mass of protein.
A procedure for transaminating proteins and removing the transaminated N-terminal residue has been used for studying structure-function relationship of protein (Dixon and Fields 1972, Meth. Enzymol. 25, 409-419). We show that it is convenient for measuring the relative molecular masses of proteins by measuring the glycine formed from glyoxylate during such transamination. Quinoxaline derivatives have been synthesized by the reaction of 2-oxo acids from amino acids reacting with o-phenylenediamine. 2-Oxo acids transaminated from amino acids fluoresced at around 405 nm, depending on the nature of residual side groups. The emission maximum of 3-benzyl-2-hydroxy-quinoxaline from the reaction of o-phenylenediamine with phenylpyruvate was at 363 nm. The fluorescent derivatives have been used to study conformational changes of peptides and to detect whether or not N-termini of proteins were blocked.
Glycine↗
Differential effects of 2-oxo acids on pyruvate utilization and fatty acid synthesis in rat brain.
1. The effects of 2-oxo-4-methylpentanoate, 2-oxo-3-methylbutanoate and 2-oxo-3-methylpentanoate on the activity of pyruvate dehydrogenase (EC 1.2.4.1), citrate synthase (EC 4.1.3.7), acetyl-CoA carboxylase, (EC 6.4.1.2) and fatty acid synthetase derived from the brains of 14-day-old rats were investigated. 2. The pyruvate dehydrogenase enzyme activity was competitively inhibited by 2-oxo-3-methylbutanoate with respect to pyruvate with a K(i) of 2.04mm but was unaffected by 2-oxo-4-methylpentanoate or 2-oxo-3-methylpentanoate. 3. The citrate synthase activity was inhibited competitively (with respect to acetyl-CoA) by 2-oxo-4-methylpentanoate (K(i)~7.2mm) and 2-oxo-3-methylbutanoate (K(i)~14.9mm) but not by 2-oxo-3-methylpentanoate. 4. The acetyl-CoA carboxylase activity was not inhibited significantly by any of the 2-oxo acids investigated. 5. The fatty acid synthetase activity was competitively inhibited (with respect to acetyl-CoA) by 2-oxo-4-methylpentanoate (K(i)~930mum) and 2-oxo-3-methylpentanoate (K(i)~3.45mm) but not by 2-oxo-3-methylbutanoate. 6. Preliminary experiments indicate that 2-oxo-4-methylpentanoate and 2-oxo-3-phenylpropionate (phenylpyruvate) significantly inhibit the ability of intact brain mitochondria from 14-day-old rats to oxidize pyruvate. 7. The results are discussed with reference to phenylketonuria and maple-syrup-urine disease. A biochemical mechanism is proposed to explain the characteristics of these diseases.
Acetyl-CoA Carboxylase↗
Vitamin B6 in mental deficiency: xanthurenic acid excretion in phenylketonurics.
Explore the source record for details and available documents.
Body Fluids↗
[Phenylpyruvic oligophrenia and tyrosinosis. Biochemical research on one family (apropos of a family originally from a village in Southern Italy)].
Explore the source record for details and available documents.
Adult↗
Kynurenine aminotransferases in the rat. Localization and characterization.
Kynurenine-2-oxoglutarate aminotransferase (kynurenine specific, designated here KAT-II) and kynurenine pyruvate aminotransferase (designated here KAT-I) activities were detected in the kidney using 2 microM kynurenine. The major activities were performed by KAT-II and the contributi-n of KAT-I is about 1/15. KAT-I activity was detected in all organs tested. The liver showed the highest KAT-I activity, however, the highest activity of glutamine transaminase-K (GTK) was detected in the kidney. KAT-I activity was well corresponded with GTK activity in all organs except liver. KAT-I or GTK activity of crude extract didn't inhibited by addition of glutamine either kynurenine. KAT-I or GTK activity of purified preparation, however, inhibited strongly addition of glutamine either kynurenine. KAT-I and GTK showed different pH optimum profile, but purified and crude preparation of those were similar. Phenylpyruvate or 2-oxo-4-methiolbutyrate reduced the inhibition of purified KAT-I activity by glutamine using 2 microM kynurenine. Phenylpyruvate changed the Km value for kynurenine and Vmax, suggesting conformational change of the enzyme.
Amino Acids↗
Crystal structures of glutamine:phenylpyruvate aminotransferase from Thermus thermophilus HB8: induced fit and substrate recognition.
The following three-dimensional structures of three forms of glutamine:phenylpyruvate aminotransferase from Thermus thermophilus HB8 have been determined and represent the first x-ray analysis of the enzyme: the unliganded pyridoxal 5'-phosphate form at 1.9 A resolution and two complexes with 3-phenylpropionate and alpha-keto-gamma-methylthiobutyrate at 2.35 and 2.6 A resolution, respectively. The enzyme shows high activity toward phenylalanine, tyrosine, tryptophan, kynurenine, methionine, and glutamine. The enzyme is a homodimer, and each subunit is divided into an N-terminal arm and small and large domains. Based on its folding, the enzyme belongs to fold type I, aminotransferase subclass Ib. The subclass I aminotransferases whose structures have so far been determined exhibit a large movement of the small domain region upon binding of a substrate. Similarly, the glutamine:phenylpyruvate aminotransferase undergoes a large movement in part of the small domain to close the active site. The active-site pocket has a shape and size suitable to enclose the side chain of an aromatic amino acid or that of methionine. The inner side of the pocket is mostly hydrophobic, but also has polar sites. The kynurenine complex generated by computer modeling fits the pocket of the enzyme and its hydrophilic groups interact with the polar sites of the pocket.
Protein Conformation↗
Long-term management of a case of carbamyl phosphate synthetase deficiency using ketanalogues and hydroxyanalogues of essential amino acids.
A 13-year-old girl with congenital deficiency of carbamyl phosphate synthetase has been treated intermittently for one year with a restricted protein diet supplemented by various mixtures of the alpha-ketoanalogues of valine, leucine, isoleucine, and phenylalanine, the D,L-alpha-hydroxyanalogue of methionine, and five amino acids (lysine, arginine, histidine, threonine and tryptophan). Numerous adjustments in the composition of this mixture were made. Eventually normal levels of plasma ammonia and most amino acids were achieved, with three exceptions: slightly increased glutamine, pronounced alloisoleucinemia, and persistently low phenylalanine. Alloisoleucine was shown not to be incorporated into plasma protein and not to be excreted in the urine; hence this abnormality was viewed as being clinically insiginificant. Hypophenylalaninemia was unexplained, and failed to respond to increased phenylpyruvate dosage or phenylalanine itself; renal clearance of phenylalanine was high but could not account for the low plasma level. Compared to the pretreatment period her clinical status has improved markedly. Physical and mental development has continued at the same rate. Temporary withdrawal of the supplements led to prompt increases in plasma ammonia, glutamine, and alanine. We conclude that this therapy provides safe and effective long-term management for this patient's disorder and may be useful in other cases of congenital hyperammonemia.
Adolescent↗
Chloroplasts of higher plants synthesize L-phenylalanine via L-arogenate.
The specific enzymological route of L-phenylalanine biosynthesis has not been established in any higher plant system. The possible pathway routes that have been identified in microorganisms utilize either phenylpyruvate or L-arogenate as a unique intermediate. We now report the presence of arogenate dehydratase (which converts L-arogenate to L-phenylalanine) in cultured-cell populations of Nicotiana silvestris. Prephenate dehydratase (which converts prephenate to phenylpyruvate) was not detected. Arogenate dehydratase was also found in washed spinach chloroplasts, and these data add to emerging evidence in support of the existence in the plastidial compartment of a complete assembly of enzymes comprising aromatic amino acid biosynthesis. Arogenate dehydratase from tobacco and spinach were both specific for L-arogenate, inhibited by L-phenylalanine, and activated by L-tyrosine. Apparent Km values for L-arogenate (0.3 X 10(-3) M), pH optima (pH 8.5-9.5), and temperature optima for catalysis (32-34 degrees C) were also similar.
Allosteric Regulation↗
[Degradation of L-phenylalanine and of aromatic carboxylic acids by chloridazon-degrading bacteria. Combination of side chain degradation and dioxygenase pathway].
Strain N of Chloridazon-degrading bacteria degrades phenylalanine via cis-2,3-dihydro-2,3-dihydroxyphenylalanine,2,3-dihydroxyphenylalanine aspartate and 4-hydroxy-2-oxovalerate [Hoppe-Seyler's Z. Physiol. Chem. 360, 957--969, (1979); Biochem. J. 194, 679--684 (1981)]. cis-2,3-Dihydro-2,3-dihydroxyphenylalanine and 2,3-dihydroxyphenylalanine as well as phenylpyruvate, cis-2,3-dihydro-2,3-dihydroxyphenylpyruvate, 2,3-dihydroxyphenylpyruvate, cis-2,3-dihydro-2,3-dihydroxyphenylacetate, 2,3-dihydroxyphenylacetate and 2,3-dihydroxybenzaldehyde are detectable in the medium of strain E during growth on phenylalanine. Incubation with phenylacetate, 3-phenylpropionate or 4-phenylbutyrate leads to the accumulation of the corresponding cis-2,3-dihydro-2,3-dihydroxyphenyl derivatives. These compounds are transformed with dihydrodiol dehydrogenase to 2,3-dihydroxyphenylacetate, 3-(2,3-dihydroxyphenyl)propionate and 4-(2,3-dihydroxyphenyl)-butyrate, 3-(2,3-dihydroxyphenyl)propionate is attacked by a catechol 2,3-dioxygenase and the meta-cleavage product is again cleaved by a hydrolase yielding succinate. In a similar reaction sequence the degradation of 4-phenylbutyrate leads to the formation of glutarate. From the growth medium of strain E on phenylacetate also small amounts of 2-, 3- and 4-hydroxyphenylacetate were isolated. Resting cells were shown to metabolize 3- and 4-hydroxyphenylacetate via homogentisate and 3,4-dihydroxyphenylacetate. In the culture medium of strain K2AP benzoate could be detected. Pathways for the degradation of phenylalanine and aromatic carboxylic acids in chloridazon degrading bacteria are proposed.
Bacteria↗
Evaluation of the PaT Stat Kinetic UV Test set for the determination of phenylalanine and tyrosine in serum or plasma.
We have evaluated the PaT Stat Kinetic UV Test Kit for the simultaneous determination of phenylalanine (Phe) and tyrosine (Tyr) in plasma or serum. The Phe and Tyr concentrations measured with the kit show a coefficient of variation of about 15% for both within- and between-day determinations. The assays for both Phe and Tyr are linear to concentrations of at least 18 mg/dL without predilution of the specimen. Concentration differences of as little as 0.5 mg/dL are distinguishable. No significant interference was found from either phenylpyruvate or phenyllactate at levels up to 0.5 mM, nor from bilirubin, haemoglobin, or triglycerides at levels well above those generally found in clinical specimens. A comparative study of 70 clinical specimens, using the kit method and an amino acid analyzer (AAA) showed a linear relationship. Least-squares analysis of the data yielded the following parameters (AAA as reference): slope = 0.93 to 1.00, intercept = 0.04 to 0.21, correlation coefficient = 0.97 to 0.98. We conclude that the kit is suitable for the determination of Phe and Tyr in plasma or serum and can enable any laboratory equipped with a recording UV-spectrophotometer to assay these two amino acids for the dietary management of PKU.
Adult↗
Enzymological features of aromatic amino acid biosynthesis reflect the phylogeny of mycoplasmas.
Acholeplasma laidlawii possesses a biochemical pathway for tyrosine and phenylalanine biosynthesis, while Mycoplasma iowae and Mycoplasma gallinarum do not. The detection of 7-phospho-2-dehydro-3-deoxy-D-arabino-heptonate (DAHP) synthase (EC 4.1.2.15), dehydro-shikimate reductase (EC 1.1.1.25) and 3-enol-pyruvoylshikimate-5-phosphate synthase (EC 2.5.1.19) activities in cell-free extracts established the presence in A. laidlawii of a functional shikimate pathway. L-Phenylalanine synthesis occurs solely through the phenylpyruvate route via prephenate dehydratase (EC 4.2.1.51), no arogenate dehydratase activity being found. Although arogenate dehydrogenase was detected, L-tyrosine synthesis appears to occur mainly through the 4-hydroxyphenylpyruvate route, via prephenate dehydrogenase (EC 1.3.1.12), which utilized NAD+ as a preferred coenzyme substrate. L-Tyrosine was found to be the key regulatory molecule governing aromatic biosynthesis. DAHP synthase was feedback inhibited by L-tyrosine, but not by L-phenylalanine or L-tryptophan; L-tyrosine was a potent feedback inhibitor of prephenate dehydrogenase and an allosteric activator of prephenate dehydratase. Chorismate mutase (EC 5.4.99.5) was sensitive to product inhibition by prephenate. Prephenate dehydratase was feedback inhibited by L-phenylalanine. It was also activated by hydrophobic amino acids (L-valine, L-isoleucine and L-methionine), similar to results previously found in a number of other genera that share the Gram-positive line of phylogenetic descent. Aromatic-pathway-encoded cistrons present in saprophytic large-genome mycoplasmas may have been eliminated in the parasitic small-genome mycoplasmas.
3-Deoxy-7-Phosphoheptulonate Synthase↗
Phenylketonuria treated with a high phenylalanine intake and casein-hydrolysate/aminoacid mixtures.
Explore the source record for details and available documents.
Amino Acids↗
Gas chromatographic-mass spectrometric screening for organic acidemias using dried urine filter paper: determination of alpha-ketoacids.
There are several organic acid disorders that require information on alpha-ketoacids, such as maple syrup urine disease or alpha-ketoadipic acidemia. The recovery, stability and diagnostic availability of alpha-ketoacids in dried urine filter paper analyzed by GC-MS with oxime-trimethylsilyl derivatization was studied for organic acidemia screening. The recovery of all nine types of alpha-ketoacids tested, but for phenylpyruvate, 2-ketoadipate, and p-OH-phenylpyruvate, from filter paper samples was acceptable. The stability of pyruvate, branched-chain alpha-ketoacids, alpha-ketoadipate and alpha-ketoglutarate was stable for at least 28 days, although some alpha-ketoacids such as succinylacetone were unstable. It indicated it was difficult to diagnose only tyrosinemia type 1 among nine specimens from organic acidemia patients tested. The method could be applied to global organic acidemia screening.
Acids↗
Crystallization and characterization of human liver kynurenine--glyoxylate aminotransferase. Identity with alanine--glyoxylate aminotransferase and serine--pyruvate aminotransferase.
Kynurenine-glyoxylate aminotransferase, alanine-glyoxylate aminotransferase and serine-pyruvate aminotransferase were co-purified and crystallized as yellow cubes from human liver particulate fraction. The crystalline enzyme was homogeneous by the criteria of electrophoresis, isoelectric focusing, gel filtration, sucrose-density-gradient centrifugation and analytical ultracentrifugation. The molecular weight of the enzyme was calculated as approx. 90000, 89000 and 99000 by the use of gel filtration, analytical ultracentrifugation and sucrose-density-gradient centrifugation respectively, with two identical subunits. The enzyme has a s(20,w) value of 5.23S, an isoelectric point of 8.3 and a pH optimum between 9.0 and 9.5. The enzyme solution showed absorption maxima at 280 and 420nm. The enzyme catalysed transamination between several l-amino acids and pyruvate or glyoxylate. The order of effectiveness of amino acids was alanine>serine>glutamine>glutamate>methionine>kynurenine = phenylalanine = asparagine>valine>histidine>lysine>leucine>isoleucine>arginine>tyrosine = threonine>aspartate, with glyoxylate as amino acceptor. The enzyme was active with glyoxylate, oxaloacetate, hydroxypyruvate, pyruvate, 4-methylthio-2-oxobutyrate and 2-oxobutyrate, but showed little activity with phenylpyruvate, 2-oxoglutarate and 2-oxoadipate, with kynurenine as amino donor. Kynurenine-glyoxylate aminotransferase activity was competitively inhibited by the addition of l-alanine or l-serine. From these results we conclude that kynurenine-glyoxylate aminotransferase, alanine-glyoxylate aminotransferase and serine-pyruvate aminotransferase activities of human liver are catalysed by a single protein. Kinetic parameters for the kynurenine-glyoxylate aminotransferase, alanine-glyoxylate aminotransferase, serine-pyruvate aminotransferase and alanine-hydroxypyruvate aminotransferase reactions of the enzyme are presented.
Aged↗
Exploitation of the broad specificity of the membrane-bound isoenzyme of lactate dehydrogenase for direct selection of null mutants in Neisseria gonorrhoeae.
Lactic acid is readily utilized as a carbon and energy source by Neisseria gonorrhoeae. The oxidation of lactate is coupled to electron transport via a membrane-bound lactate dehydrogenase (iLDH) which is independent of pyridine nucleotide. The broad substrate specificity of iLDH endows N. gonorrhoeae with the novel ability to convert phenyllactate to L-phenylalanine via phenylpyruvate. N. gonorrhoeae ATCC 27628 typifies a class of clinical isolate whose growth is inhibited by phenylpyruvate (or L-phenylalanine). Exploiting resistance to growth inhibition by phenyllactate as a strategy of positive selection, mutant derivatives of strain ATCC 27628 lacking iLDH activity were readily obtained. These mutants are incapable of oxidizing phenyllactate, and lack the parent-strain ability to reduce c-type cytochromes in the presence of lactate, phenyllactate or 4-hydroxyphenyllactate. They retain, however, a cytoplasmic NAD(+)-linked lactate dehydrogenase (nLDH). Since the mutants retained the ability to grow on lactate as a sole source of carbon, nLDH presumably can function in an opposite-to-normal physiological direction in the absence of iLDH. This would explain the failure to isolate iLDH-deficient mutants by selection for inability to grow on lactate.
Drug Resistance, Microbial↗
UTILIZATION OF AROMATIC AMINO ACIDS BY HYDROGENOMONAS FACILIS.
DeCicco, B. T. (Rutgers, The State University, New Brunswick, N.J.), and W. W. Umbreit. Utilization of aromatic amino acids by Hydrogenomonas facilis. J. Bacteriol. 88:1590-1594. 1964.-An auxotrophic mutant of Hydrogenomonas facilis was isolated which requires tryptophan, phenylalanine, and p-aminobenzoic acid (PABA) for growth. With glucose as the main carbon and energy source, the quantitative requirements for tryptophan and PABA were at normal microgram levels, but the requirement for phenylalanine was very large and approached substrate concentrations. The large phenylalanine requirement is due to a rapid oxidation and degradation of phenylalanine by the mutant. The utilization of both phenylalanine and glucose is adaptive, and the presence of phenylalanine partially inhibits the induction of the glucose-utilizing system. Wild-type H. facilis can utilize either phenylalanine or tyrosine for growth. Tracer studies indicated that during growth on phenylalanine, the aromatic ring is opened and degraded. Wild-type cells grown on either phenylalanine or tyrosine can oxidize phenylalanine, tyrosine, or phenylpyruvate without a lag. Another inducible pathway enables H. facilis to utilize either quinate or 3,4-dihydroxybenzoate for growth, and sequential adaptation studies revealed that quinate is converted to 3,4-dihydroxybenzoate during its degradation. Mutants may be obtained which can also utilize 2,5-dihydroxybenzoate for growth.
4-Aminobenzoic Acid↗