The Experts below are selected from a list of 2010 Experts worldwide ranked by ideXlab platform
Yeshayahu Katz - One of the best experts on this subject based on the ideXlab platform.
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β Phenylpyruvate and glucose uptake in isolated mouse soleus muscle and cultured c2c12 muscle cells
Journal of Cellular Biochemistry, 2003Co-Authors: Ron Benabraham, Vered Gazit, Oded Vofsi, Izahar Benshlomo, Abraham Z Reznick, Yeshayahu KatzAbstract:Previous investigation demonstrated the potential of b-Phenylpyruvate at high concentration to cause hypoglycemia in mice totally deprived of insulin. For further elucidation of the glucose-lowering mechanism, glucose uptake, and quantity of glucose transporters (GLUT1 and GLUT4) in mouse soleus muscle and C2C12 muscle cell lines were investigated following incubation with b-Phenylpyruvate in various concentrations. A marked enhancement of glucoseuptakewasdemonstratedthatpeakedat0.5and1.0mMb-Phenylpyruvateinsoleusmuscle(P <0.01)andC2C12 cells(P <0.001),respectively.Kinetic analysisinC2C12cells showedatwofold increaseinVmaxcomparedwithcontrols (P <0.001). In addition, both GLUT1 and GLUT4 levels were increased following exposure to b-Phenylpyruvate. Our findings point to a peripheral hypoglycemic effect of b-Phenylpyruvate. J. Cell. Biochem. 90: 957-963, 2003. 2003 Wiley-Liss, Inc.
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β‐Phenylpyruvate and glucose uptake in isolated mouse soleus muscle and cultured C2C12 muscle cells
Journal of cellular biochemistry, 2003Co-Authors: Ron Ben-abraham, Vered Gazit, Oded Vofsi, Abraham Z Reznick, Izahar Ben‐shlomo, Yeshayahu KatzAbstract:Previous investigation demonstrated the potential of b-Phenylpyruvate at high concentration to cause hypoglycemia in mice totally deprived of insulin. For further elucidation of the glucose-lowering mechanism, glucose uptake, and quantity of glucose transporters (GLUT1 and GLUT4) in mouse soleus muscle and C2C12 muscle cell lines were investigated following incubation with b-Phenylpyruvate in various concentrations. A marked enhancement of glucoseuptakewasdemonstratedthatpeakedat0.5and1.0mMb-Phenylpyruvateinsoleusmuscle(P
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β-Phenylpyruvate induces long-term neurobehavioral damage and brain necrosis in neonatal mice
Behavioural brain research, 2003Co-Authors: Vered Gazit, Ron Ben-abraham, Chaim G. Pick, Yeshayahu KatzAbstract:Abstract Administration of β-Phenylpyruvate at high concentrations reduces blood glucose levels and causes neurophysiological deterioration in insulin-deprived mice. We investigated whether β-Phenylpyruvate administration would cause long-term neurobehavioral and structural central neural damage in mice. Neonatal ICR mice were injected with β-Phenylpyruvate (0.5–2.5 mg/g body weight (BW)) or saline (control). Blood glucose was measured. At 43 days of age, the animals were put on a 1-week regimen of restricted water supply, after which the mice were introduced into an eight-arm maze for evaluation of spatial-memory abilities (hippocampal-related behavior). Times for visiting all eight arms and number of entries until completion of the eight-arm visits (maze criteria) were measured. The test was repeated once daily for 5 days. TUNEL assay was used for detection of brain apoptosis. β-Phenylpyruvate-treated animals (except the 0.5 mg/g group) developed hypoglycemia. Treated mice required more time to assimilate the maze structure. Mice treated with 2.5 mg/g β-Phenylpyruvate did not meet the maze criteria as compared with control ( P
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Glucose-lowering effect of beta-Phenylpyruvate in neonatal mice: a possible mechanism for phenylketonuria-related neurodegenerative changes.
Brain research. Developmental brain research, 2003Co-Authors: Vered Gazit, Ron Ben-abraham, Michael Rudin, Yeshayahu KatzAbstract:Following beta-Phenylpyruvate injection, mice developed hypoglycemia clinically manifested as tachypnea, tremor, convulsions and death. To further investigate, neonatal mice were injected with beta-Phenylpyruvate and their blood glucose determined and brain histology assessed. beta-Phenylpyruvate-injected mice exhibited higher mortality and neurophysiological changes as compared with controls, although without evidence of neural cell death. Accordingly, we hypothesize that the central neural damage in phenylketonuria might be caused by these recurrent beta-Phenylpyruvate-induced hypoglycemic events.
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Glucose-lowering effect of β-Phenylpyruvate in neonatal mice: a possible mechanism for phenylketonuria-related neurodegenerative changes
Developmental Brain Research, 2003Co-Authors: Vered Gazit, Ron Ben-abraham, Michael Rudin, Yeshayahu KatzAbstract:Following β-Phenylpyruvate injection, mice developed hypoglycemia clinically manifested as tachypnea, tremor, convulsions and death. To further investigate, neonatal mice were injected with β-Phenylpyruvate and their blood glucose determined and brain histology assessed. β-Phenylpyruvate-injected mice exhibited higher mortality and neurophysiological changes as compared with controls, although without evidence of neural cell death. Accordingly, we hypothesize that the central neural damage in phenylketonuria might be caused by these recurrent β-Phenylpyruvate-induced hypoglycemic events.
Vered Gazit - One of the best experts on this subject based on the ideXlab platform.
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β Phenylpyruvate and glucose uptake in isolated mouse soleus muscle and cultured c2c12 muscle cells
Journal of Cellular Biochemistry, 2003Co-Authors: Ron Benabraham, Vered Gazit, Oded Vofsi, Izahar Benshlomo, Abraham Z Reznick, Yeshayahu KatzAbstract:Previous investigation demonstrated the potential of b-Phenylpyruvate at high concentration to cause hypoglycemia in mice totally deprived of insulin. For further elucidation of the glucose-lowering mechanism, glucose uptake, and quantity of glucose transporters (GLUT1 and GLUT4) in mouse soleus muscle and C2C12 muscle cell lines were investigated following incubation with b-Phenylpyruvate in various concentrations. A marked enhancement of glucoseuptakewasdemonstratedthatpeakedat0.5and1.0mMb-Phenylpyruvateinsoleusmuscle(P <0.01)andC2C12 cells(P <0.001),respectively.Kinetic analysisinC2C12cells showedatwofold increaseinVmaxcomparedwithcontrols (P <0.001). In addition, both GLUT1 and GLUT4 levels were increased following exposure to b-Phenylpyruvate. Our findings point to a peripheral hypoglycemic effect of b-Phenylpyruvate. J. Cell. Biochem. 90: 957-963, 2003. 2003 Wiley-Liss, Inc.
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β‐Phenylpyruvate and glucose uptake in isolated mouse soleus muscle and cultured C2C12 muscle cells
Journal of cellular biochemistry, 2003Co-Authors: Ron Ben-abraham, Vered Gazit, Oded Vofsi, Abraham Z Reznick, Izahar Ben‐shlomo, Yeshayahu KatzAbstract:Previous investigation demonstrated the potential of b-Phenylpyruvate at high concentration to cause hypoglycemia in mice totally deprived of insulin. For further elucidation of the glucose-lowering mechanism, glucose uptake, and quantity of glucose transporters (GLUT1 and GLUT4) in mouse soleus muscle and C2C12 muscle cell lines were investigated following incubation with b-Phenylpyruvate in various concentrations. A marked enhancement of glucoseuptakewasdemonstratedthatpeakedat0.5and1.0mMb-Phenylpyruvateinsoleusmuscle(P
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β-Phenylpyruvate induces long-term neurobehavioral damage and brain necrosis in neonatal mice
Behavioural brain research, 2003Co-Authors: Vered Gazit, Ron Ben-abraham, Chaim G. Pick, Yeshayahu KatzAbstract:Abstract Administration of β-Phenylpyruvate at high concentrations reduces blood glucose levels and causes neurophysiological deterioration in insulin-deprived mice. We investigated whether β-Phenylpyruvate administration would cause long-term neurobehavioral and structural central neural damage in mice. Neonatal ICR mice were injected with β-Phenylpyruvate (0.5–2.5 mg/g body weight (BW)) or saline (control). Blood glucose was measured. At 43 days of age, the animals were put on a 1-week regimen of restricted water supply, after which the mice were introduced into an eight-arm maze for evaluation of spatial-memory abilities (hippocampal-related behavior). Times for visiting all eight arms and number of entries until completion of the eight-arm visits (maze criteria) were measured. The test was repeated once daily for 5 days. TUNEL assay was used for detection of brain apoptosis. β-Phenylpyruvate-treated animals (except the 0.5 mg/g group) developed hypoglycemia. Treated mice required more time to assimilate the maze structure. Mice treated with 2.5 mg/g β-Phenylpyruvate did not meet the maze criteria as compared with control ( P
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Glucose-lowering effect of beta-Phenylpyruvate in neonatal mice: a possible mechanism for phenylketonuria-related neurodegenerative changes.
Brain research. Developmental brain research, 2003Co-Authors: Vered Gazit, Ron Ben-abraham, Michael Rudin, Yeshayahu KatzAbstract:Following beta-Phenylpyruvate injection, mice developed hypoglycemia clinically manifested as tachypnea, tremor, convulsions and death. To further investigate, neonatal mice were injected with beta-Phenylpyruvate and their blood glucose determined and brain histology assessed. beta-Phenylpyruvate-injected mice exhibited higher mortality and neurophysiological changes as compared with controls, although without evidence of neural cell death. Accordingly, we hypothesize that the central neural damage in phenylketonuria might be caused by these recurrent beta-Phenylpyruvate-induced hypoglycemic events.
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Glucose-lowering effect of β-Phenylpyruvate in neonatal mice: a possible mechanism for phenylketonuria-related neurodegenerative changes
Developmental Brain Research, 2003Co-Authors: Vered Gazit, Ron Ben-abraham, Michael Rudin, Yeshayahu KatzAbstract:Following β-Phenylpyruvate injection, mice developed hypoglycemia clinically manifested as tachypnea, tremor, convulsions and death. To further investigate, neonatal mice were injected with β-Phenylpyruvate and their blood glucose determined and brain histology assessed. β-Phenylpyruvate-injected mice exhibited higher mortality and neurophysiological changes as compared with controls, although without evidence of neural cell death. Accordingly, we hypothesize that the central neural damage in phenylketonuria might be caused by these recurrent β-Phenylpyruvate-induced hypoglycemic events.
Michael J. Mcleish - One of the best experts on this subject based on the ideXlab platform.
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characterization of a thiamin diphosphate dependent Phenylpyruvate decarboxylase from saccharomyces cerevisiae
FEBS Journal, 2011Co-Authors: Malea M. Kneen, Razvan C. Stan, Alejandra Yep, Ryan P. Tyler, Choedchai Saehuan, Michael J. McleishAbstract:The product of the ARO10 gene from Saccharomyces cerevisiae was initially identified as a thiamine diphosphate-dependent Phenylpyruvate decarboxylase with a broad substrate specificity. It was suggested that the enzyme could be responsible for the catabolism of aromatic and branched-chain amino acids, as well as methionine. In the present study, we report the overexpression of the ARO10 gene product in Escherichia coli and the first detailed in vitro characterization of this enzyme. The enzyme is shown to be an efficient aromatic 2-keto acid decarboxylase, consistent with it playing a major in vivo role in phenylalanine, tryptophan and possibly also tyrosine catabolism. However, its substrate spectrum suggests that it is unlikely to play any significant role in the catabolism of the branched-chain amino acids or of methionine. A homology model was used to identify residues likely to be involved in substrate specificity. Site-directed mutagenesis on those residues confirmed previous studies indicating that mutation of single residues is unlikely to produce the immediate conversion of an aromatic into an aliphatic 2-keto acid decarboxylase. In addition, the enzyme was compared with the Phenylpyruvate decarboxylase from Azospirillum brasilense and the indolepyruvate decarboxylase from Enterobacter cloacae. We show that the properties of the two Phenylpyruvate decarboxylases are similar in some respects yet quite different in others, and that the properties of both are distinct from those of the indolepyruvate decarboxylase. Finally, we demonstrate that it is unlikely that replacement of a glutamic acid by leucine leads to discrimination between Phenylpyruvate and indolepyruvate, although, in this case, it did lead to unexpected allosteric activation.
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Characterization of a thiamin diphosphate‐dependent Phenylpyruvate decarboxylase from Saccharomyces cerevisiae
The FEBS journal, 2011Co-Authors: Malea M. Kneen, Razvan C. Stan, Alejandra Yep, Ryan P. Tyler, Choedchai Saehuan, Michael J. McleishAbstract:The product of the ARO10 gene from Saccharomyces cerevisiae was initially identified as a thiamine diphosphate-dependent Phenylpyruvate decarboxylase with a broad substrate specificity. It was suggested that the enzyme could be responsible for the catabolism of aromatic and branched-chain amino acids, as well as methionine. In the present study, we report the overexpression of the ARO10 gene product in Escherichia coli and the first detailed in vitro characterization of this enzyme. The enzyme is shown to be an efficient aromatic 2-keto acid decarboxylase, consistent with it playing a major in vivo role in phenylalanine, tryptophan and possibly also tyrosine catabolism. However, its substrate spectrum suggests that it is unlikely to play any significant role in the catabolism of the branched-chain amino acids or of methionine. A homology model was used to identify residues likely to be involved in substrate specificity. Site-directed mutagenesis on those residues confirmed previous studies indicating that mutation of single residues is unlikely to produce the immediate conversion of an aromatic into an aliphatic 2-keto acid decarboxylase. In addition, the enzyme was compared with the Phenylpyruvate decarboxylase from Azospirillum brasilense and the indolepyruvate decarboxylase from Enterobacter cloacae. We show that the properties of the two Phenylpyruvate decarboxylases are similar in some respects yet quite different in others, and that the properties of both are distinct from those of the indolepyruvate decarboxylase. Finally, we demonstrate that it is unlikely that replacement of a glutamic acid by leucine leads to discrimination between Phenylpyruvate and indolepyruvate, although, in this case, it did lead to unexpected allosteric activation.
Marcos Antonio De Morais - One of the best experts on this subject based on the ideXlab platform.
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The yeast Dekkera bruxellensis genome contains two orthologs of the ARO10 gene encoding for Phenylpyruvate decarboxylase
World Journal of Microbiology and Biotechnology, 2012Co-Authors: Anna Theresa Souza Liberal, Marcelo Falsarella Carazzolle, Gonçalo Amarante Pereira, Diogo Ardaillon Simões, Marcos Antonio De MoraisAbstract:The yeast Dekkera bruxellensis possesses important physiological traits that enable it to grow in industrial environments as either spoiling yeast of wine production or a fermenting strain used for lambic beer, or fermenting yeast in the bioethanol production process. In this work, in silico analysis of the Dekkera genome database allowed the identification of two paralogous genes encoding for Phenylpyruvate decarboxylase ( DbARO10 ) that represents a unique trait among the hemiascomycetes. The molecular analysis of the theoretical protein confirmed its protein identity. Upon cultivation of the cell in medium containing Phenylpyruvate, both increases in gene expression and in Phenylpyruvate decarboxylase activity were observed. Both genes were differentially expressed depending on the culture condition and the type of metabolism, which indicated the difference in the biological function of their corresponding proteins. The importance of the duplicated DbARO10 genes in the D. bruxellensis genome was discussed and represents the first effort to understand the production of flavor by this yeast.
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Identification and characterization of Phenylpyruvate decarboxylase genes in Saccharomyces cerevisiae
Applied and environmental microbiology, 2003Co-Authors: Zeynep Vuralhan, Marcos Antonio De Morais, Siew Leng Tai, Matthew D W Piper, Jack T. PronkAbstract:Catabolism of amino acids via the Ehrlich pathway involves transamination to the corresponding α-keto acids, followed by decarboxylation to an aldehyde and then reduction to an alcohol. Alternatively, the aldehyde may be oxidized to an acid. This pathway is functional in Saccharomyces cerevisiae, since during growth in glucose-limited chemostat cultures with phenylalanine as the sole nitrogen source, phenylethanol and phenylacetate were produced in quantities that accounted for all of the phenylalanine consumed. Our objective was to identify the structural gene(s) required for the decarboxylation of Phenylpyruvate to phenylacetaldehyde, the first specific step in the Ehrlich pathway. S. cerevisiae possesses five candidate genes with sequence similarity to genes encoding thiamine diphosphate-dependent decarboxylases that could encode this activity: YDR380w/ARO10, YDL080C/THI3, PDC1, PDC5, and PDC6. Phenylpyruvate decarboxylase activity was present in cultures grown with phenylalanine as the sole nitrogen source but was absent from ammonia-grown cultures. Furthermore, the transcript level of one candidate gene (ARO10) increased 30-fold when phenylalanine replaced ammonia as the sole nitrogen source. 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. There was also an alternative activity with a higher capacity but lower affinity for Phenylpyruvate. The candidate gene THI3 did not itself encode an active Phenylpyruvate decarboxylase but was required along with one or more pyruvate decarboxylase genes (PDC1, PDC5, and PDC6) for the alternative activity. The Km and Vmax values of the two activities differed, showing that Aro10p is the physiologically relevant Phenylpyruvate decarboxylase in wild-type cells. Modifications to this gene could therefore be important for metabolic engineering of the Ehrlich pathway.
Ron Ben-abraham - One of the best experts on this subject based on the ideXlab platform.
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β‐Phenylpyruvate and glucose uptake in isolated mouse soleus muscle and cultured C2C12 muscle cells
Journal of cellular biochemistry, 2003Co-Authors: Ron Ben-abraham, Vered Gazit, Oded Vofsi, Abraham Z Reznick, Izahar Ben‐shlomo, Yeshayahu KatzAbstract:Previous investigation demonstrated the potential of b-Phenylpyruvate at high concentration to cause hypoglycemia in mice totally deprived of insulin. For further elucidation of the glucose-lowering mechanism, glucose uptake, and quantity of glucose transporters (GLUT1 and GLUT4) in mouse soleus muscle and C2C12 muscle cell lines were investigated following incubation with b-Phenylpyruvate in various concentrations. A marked enhancement of glucoseuptakewasdemonstratedthatpeakedat0.5and1.0mMb-Phenylpyruvateinsoleusmuscle(P
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β-Phenylpyruvate induces long-term neurobehavioral damage and brain necrosis in neonatal mice
Behavioural brain research, 2003Co-Authors: Vered Gazit, Ron Ben-abraham, Chaim G. Pick, Yeshayahu KatzAbstract:Abstract Administration of β-Phenylpyruvate at high concentrations reduces blood glucose levels and causes neurophysiological deterioration in insulin-deprived mice. We investigated whether β-Phenylpyruvate administration would cause long-term neurobehavioral and structural central neural damage in mice. Neonatal ICR mice were injected with β-Phenylpyruvate (0.5–2.5 mg/g body weight (BW)) or saline (control). Blood glucose was measured. At 43 days of age, the animals were put on a 1-week regimen of restricted water supply, after which the mice were introduced into an eight-arm maze for evaluation of spatial-memory abilities (hippocampal-related behavior). Times for visiting all eight arms and number of entries until completion of the eight-arm visits (maze criteria) were measured. The test was repeated once daily for 5 days. TUNEL assay was used for detection of brain apoptosis. β-Phenylpyruvate-treated animals (except the 0.5 mg/g group) developed hypoglycemia. Treated mice required more time to assimilate the maze structure. Mice treated with 2.5 mg/g β-Phenylpyruvate did not meet the maze criteria as compared with control ( P
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Glucose-lowering effect of beta-Phenylpyruvate in neonatal mice: a possible mechanism for phenylketonuria-related neurodegenerative changes.
Brain research. Developmental brain research, 2003Co-Authors: Vered Gazit, Ron Ben-abraham, Michael Rudin, Yeshayahu KatzAbstract:Following beta-Phenylpyruvate injection, mice developed hypoglycemia clinically manifested as tachypnea, tremor, convulsions and death. To further investigate, neonatal mice were injected with beta-Phenylpyruvate and their blood glucose determined and brain histology assessed. beta-Phenylpyruvate-injected mice exhibited higher mortality and neurophysiological changes as compared with controls, although without evidence of neural cell death. Accordingly, we hypothesize that the central neural damage in phenylketonuria might be caused by these recurrent beta-Phenylpyruvate-induced hypoglycemic events.
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Glucose-lowering effect of β-Phenylpyruvate in neonatal mice: a possible mechanism for phenylketonuria-related neurodegenerative changes
Developmental Brain Research, 2003Co-Authors: Vered Gazit, Ron Ben-abraham, Michael Rudin, Yeshayahu KatzAbstract:Following β-Phenylpyruvate injection, mice developed hypoglycemia clinically manifested as tachypnea, tremor, convulsions and death. To further investigate, neonatal mice were injected with β-Phenylpyruvate and their blood glucose determined and brain histology assessed. β-Phenylpyruvate-injected mice exhibited higher mortality and neurophysiological changes as compared with controls, although without evidence of neural cell death. Accordingly, we hypothesize that the central neural damage in phenylketonuria might be caused by these recurrent β-Phenylpyruvate-induced hypoglycemic events.