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Christopher J. Schofield - One of the best experts on this subject based on the ideXlab platform.
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L-DELTA -(ALPHA -AMINOADIPOYL)-L-CYSTEINYL-D-Valine SYNTHETASE : THIOESTERIFICATION OF Valine IS NOT OBLIGATORY FOR PEPTIDE BOND FORMATION
Biochemistry, 1997Co-Authors: Chia-yang Shiau, Michael F. Byford, Jack E Baldwin, Robin T. Aplin, Christopher J. SchofieldAbstract:l-δ-(α-Aminoadipoyl)-l-cysteinyl-d-Valine (ACV) synthetase is probably the simplest known peptide synthetase in terms of the number of reactions catalyzed. In the “thiol-template” proposal for nonribosomal peptide synthesis, a key step is transfer of aminoacyl groups derived from the substrates to enzyme-bound thiols prior to peptide bond formation. No incorporation of 18O was seen in AMP isolated from the reaction mixture when di[18O]Valine was incubated with relatively large amounts of active synthetase and MgATP. We therefore utilized di[18O]Valine as a substrate for the biosynthesis of the diastereomeric dipeptides l-O-(methylserinyl)-l-Valine and l-O-(methylserinyl)-d-Valine [Shiau, C.-Y., Baldwin, J. E., Byford, M. F., Sobey, W. J., & Schofield, C. J. (1995) FEBS Lett. 358, 97−100]. In the l-O-(methylserinyl)-l-Valine product, no significant loss of 18O was observed. However, in the l-O-(methylserinyl)-d-Valine product, a significant loss of one or both 18O labels was observed. Thus, both peptide bo...
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L-delta-(alpha-Aminoadipoyl)-L-cysteinyl-D-Valine synthetase: thioesterification of Valine is not obligatory for peptide bond formation.
Biochemistry, 1997Co-Authors: Chia-yang Shiau, Michael F. Byford, Jack E Baldwin, Robin T. Aplin, Christopher J. SchofieldAbstract:L-delta-(alpha-Aminoadipoyl)-L-cysteinyl-D-Valine (ACV) synthetase is probably the simplest known peptide synthetase in terms of the number of reactions catalyzed. In the "thiol-template" proposal for nonribosomal peptide synthesis, a key step is transfer of aminoacyl groups derived from the substrates to enzyme-bound thiols prior to peptide bond formation. No incorporation of 18O was seen in AMP isolated from the reaction mixture when di[18O]Valine was incubated with relatively large amounts of active synthetase and MgATP. We therefore utilized di[18O]Valine as a substrate for the biosynthesis of the diastereomeric dipeptides L-O-(methylserinyl)-L-Valine and L-O-(methylserinyl)-D-Valine [Shiau, C.-Y., Baldwin, J. E., Byford, M. F., Sobey, W. J., & Schofield, C. J. (1995) FEBS Lett. 358, 97-100]. In the L-O-(methylserinyl)-L-Valine product, no significant loss of 18O was observed. However, in the L-O-(methylserinyl)-D-Valine product, a significant loss of one or both 18O labels was observed. Thus, both peptide bond formation and the epimerization of the Valine residue can both occur before formation of any thioester bond to the Valine carboxylate in the biosynthesis of these dipeptides. The usual qualitative test for thioesterification of substrates to the synthetase, lability of enzyme-bound radiolabeled amino acid to performic acid, proved inconclusive in our hands. These results require a new mechanism for the enzymic synthesis of L-O-(methylserinyl)-L-Valine and L-O-(methylserinyl)-D-Valine and imply that a revised mechanism for ACV synthesis is also required.
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Studies on the exchange of Valine-oxygen during the biosynthesis of δ-(L-α-Aminoadipoyl)-L-cysteinyl-D-Valine.
Tetrahedron, 1992Co-Authors: Jack E Baldwin, Robert M. Adlington, Juliette W. Bird, Robert A. Field, Niamh M. O''callaghan, Christopher J. SchofieldAbstract:Abstract Incorporation of [4-2H6,18O2]-Valine into δ-(L)-α-aminoadipoyl)-L-cysteinyl-D-Valine (ACV), by intact cells of Cephalosporium acremonium, demonstrated the intracellular exchange of one and both Valine oxygen atoms. Incubation of [18O2]-Valine with the purified ACV synthetase from C. acremonium gave exclusive incorporation of a single 18O label into ACV, consistent witheffectively non-reversible formation of a covalent valinoyl-ACV synthetase intermediate under in vitro conditions.
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Exchange of Valine-oxygen during the biosynthesis of δ-(L-α-aminoadipoyl)-L-cysteinyl-D-Valine
J. Chem. Soc. Chem. Commun., 1991Co-Authors: Jack E Baldwin, Robert A. Field, Christopher J. SchofieldAbstract:Incubation of [18O2]Valine with purified ACV synthetase from Cephalosporium acremonium gave exclusive incorporation of a single 18O label into δ-(L-α-aminoadipoyl)-L-cysteinyl-D-Valine (ACV), consistent with the formation of a covalent valinoyl-ACV synthetase complex.
Roger A. Vaughan - One of the best experts on this subject based on the ideXlab platform.
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Effect of Valine on myotube insulin sensitivity and metabolism with and without insulin resistance
Molecular and Cellular Biochemistry, 2020Co-Authors: Madison E. Rivera, Emily S. Lyon, Michele A. Johnson, Kyle L. Sunderland, Roger A. VaughanAbstract:Population data have consistently demonstrated a correlation between circulating branched-chain amino acids (BCAA) and insulin resistance. Most recently Valine catabolite, 3-hydroxyisobutyrate, has emerged as a potential cause of BCAA-mediated insulin resistance; however, it is unclear if Valine independently promotes insulin resistance. It is also unclear if excess Valine influences the ability of cells to degrade BCAA. Therefore, this study investigated the effect of Valine on muscle insulin signaling and related metabolism in vitro. C2C12 myotubes were treated with varying concentrations (0.5 mM–2 mM) of Valine for up to 48 h. qRT-PCR and western blot were used to measure metabolic gene and protein expression, respectively. Insulin sensitivity (indicated by pAkt:Akt), metabolic gene and protein expression, and cell metabolism were also measured following Valine treatment both with and without varying levels of insulin resistance. Mitochondrial and glycolytic metabolism were measured via oxygen consumption and extracellular acidification rate, respectively. Valine did not alter regulators of mitochondrial biogenesis or glycolysis; however, Valine reduced branched-chain alpha-keto acid dehydrogenase a ( Bckdha ) mRNA (but not protein) expression which was exacerbated by insulin resistance. Valine treatment had no effect on pAkt:Akt following either acute or 48-h treatment, regardless of insulin stimulation or varying levels of insulin resistance. In conclusion, despite consistent population data demonstrating a relationship between circulating BCAA (and related metabolites) and insulin resistance, Valine does not appear to independently alter insulin sensitivity or worsen insulin resistance in the myotube model of skeletal muscle.
Madison E. Rivera - One of the best experts on this subject based on the ideXlab platform.
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Effect of Valine on myotube insulin sensitivity and metabolism with and without insulin resistance
Molecular and Cellular Biochemistry, 2020Co-Authors: Madison E. Rivera, Emily S. Lyon, Michele A. Johnson, Kyle L. Sunderland, Roger A. VaughanAbstract:Population data have consistently demonstrated a correlation between circulating branched-chain amino acids (BCAA) and insulin resistance. Most recently Valine catabolite, 3-hydroxyisobutyrate, has emerged as a potential cause of BCAA-mediated insulin resistance; however, it is unclear if Valine independently promotes insulin resistance. It is also unclear if excess Valine influences the ability of cells to degrade BCAA. Therefore, this study investigated the effect of Valine on muscle insulin signaling and related metabolism in vitro. C2C12 myotubes were treated with varying concentrations (0.5 mM–2 mM) of Valine for up to 48 h. qRT-PCR and western blot were used to measure metabolic gene and protein expression, respectively. Insulin sensitivity (indicated by pAkt:Akt), metabolic gene and protein expression, and cell metabolism were also measured following Valine treatment both with and without varying levels of insulin resistance. Mitochondrial and glycolytic metabolism were measured via oxygen consumption and extracellular acidification rate, respectively. Valine did not alter regulators of mitochondrial biogenesis or glycolysis; however, Valine reduced branched-chain alpha-keto acid dehydrogenase a ( Bckdha ) mRNA (but not protein) expression which was exacerbated by insulin resistance. Valine treatment had no effect on pAkt:Akt following either acute or 48-h treatment, regardless of insulin stimulation or varying levels of insulin resistance. In conclusion, despite consistent population data demonstrating a relationship between circulating BCAA (and related metabolites) and insulin resistance, Valine does not appear to independently alter insulin sensitivity or worsen insulin resistance in the myotube model of skeletal muscle.
Jack E Baldwin - One of the best experts on this subject based on the ideXlab platform.
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L-DELTA -(ALPHA -AMINOADIPOYL)-L-CYSTEINYL-D-Valine SYNTHETASE : THIOESTERIFICATION OF Valine IS NOT OBLIGATORY FOR PEPTIDE BOND FORMATION
Biochemistry, 1997Co-Authors: Chia-yang Shiau, Michael F. Byford, Jack E Baldwin, Robin T. Aplin, Christopher J. SchofieldAbstract:l-δ-(α-Aminoadipoyl)-l-cysteinyl-d-Valine (ACV) synthetase is probably the simplest known peptide synthetase in terms of the number of reactions catalyzed. In the “thiol-template” proposal for nonribosomal peptide synthesis, a key step is transfer of aminoacyl groups derived from the substrates to enzyme-bound thiols prior to peptide bond formation. No incorporation of 18O was seen in AMP isolated from the reaction mixture when di[18O]Valine was incubated with relatively large amounts of active synthetase and MgATP. We therefore utilized di[18O]Valine as a substrate for the biosynthesis of the diastereomeric dipeptides l-O-(methylserinyl)-l-Valine and l-O-(methylserinyl)-d-Valine [Shiau, C.-Y., Baldwin, J. E., Byford, M. F., Sobey, W. J., & Schofield, C. J. (1995) FEBS Lett. 358, 97−100]. In the l-O-(methylserinyl)-l-Valine product, no significant loss of 18O was observed. However, in the l-O-(methylserinyl)-d-Valine product, a significant loss of one or both 18O labels was observed. Thus, both peptide bo...
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L-delta-(alpha-Aminoadipoyl)-L-cysteinyl-D-Valine synthetase: thioesterification of Valine is not obligatory for peptide bond formation.
Biochemistry, 1997Co-Authors: Chia-yang Shiau, Michael F. Byford, Jack E Baldwin, Robin T. Aplin, Christopher J. SchofieldAbstract:L-delta-(alpha-Aminoadipoyl)-L-cysteinyl-D-Valine (ACV) synthetase is probably the simplest known peptide synthetase in terms of the number of reactions catalyzed. In the "thiol-template" proposal for nonribosomal peptide synthesis, a key step is transfer of aminoacyl groups derived from the substrates to enzyme-bound thiols prior to peptide bond formation. No incorporation of 18O was seen in AMP isolated from the reaction mixture when di[18O]Valine was incubated with relatively large amounts of active synthetase and MgATP. We therefore utilized di[18O]Valine as a substrate for the biosynthesis of the diastereomeric dipeptides L-O-(methylserinyl)-L-Valine and L-O-(methylserinyl)-D-Valine [Shiau, C.-Y., Baldwin, J. E., Byford, M. F., Sobey, W. J., & Schofield, C. J. (1995) FEBS Lett. 358, 97-100]. In the L-O-(methylserinyl)-L-Valine product, no significant loss of 18O was observed. However, in the L-O-(methylserinyl)-D-Valine product, a significant loss of one or both 18O labels was observed. Thus, both peptide bond formation and the epimerization of the Valine residue can both occur before formation of any thioester bond to the Valine carboxylate in the biosynthesis of these dipeptides. The usual qualitative test for thioesterification of substrates to the synthetase, lability of enzyme-bound radiolabeled amino acid to performic acid, proved inconclusive in our hands. These results require a new mechanism for the enzymic synthesis of L-O-(methylserinyl)-L-Valine and L-O-(methylserinyl)-D-Valine and imply that a revised mechanism for ACV synthesis is also required.
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Studies on the exchange of Valine-oxygen during the biosynthesis of δ-(L-α-Aminoadipoyl)-L-cysteinyl-D-Valine.
Tetrahedron, 1992Co-Authors: Jack E Baldwin, Robert M. Adlington, Juliette W. Bird, Robert A. Field, Niamh M. O''callaghan, Christopher J. SchofieldAbstract:Abstract Incorporation of [4-2H6,18O2]-Valine into δ-(L)-α-aminoadipoyl)-L-cysteinyl-D-Valine (ACV), by intact cells of Cephalosporium acremonium, demonstrated the intracellular exchange of one and both Valine oxygen atoms. Incubation of [18O2]-Valine with the purified ACV synthetase from C. acremonium gave exclusive incorporation of a single 18O label into ACV, consistent witheffectively non-reversible formation of a covalent valinoyl-ACV synthetase intermediate under in vitro conditions.
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Exchange of Valine-oxygen during the biosynthesis of δ-(L-α-aminoadipoyl)-L-cysteinyl-D-Valine
J. Chem. Soc. Chem. Commun., 1991Co-Authors: Jack E Baldwin, Robert A. Field, Christopher J. SchofieldAbstract:Incubation of [18O2]Valine with purified ACV synthetase from Cephalosporium acremonium gave exclusive incorporation of a single 18O label into δ-(L-α-aminoadipoyl)-L-cysteinyl-D-Valine (ACV), consistent with the formation of a covalent valinoyl-ACV synthetase complex.
Qiaqing Wu - One of the best experts on this subject based on the ideXlab platform.
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accessing d Valine synthesis by improved variants of bacterial cyclohexylamine oxidase
Chemcatchem, 2018Co-Authors: Rui Gong, Xi Chen, Jinhui Feng, Qiaqing WuAbstract:Chemoenzymatic deracemization was applied to prepare d-Valine from racemic Valine ethyl ester or l-Valine ethyl ester in high yield (up to 95 %) with excellent optical purity (>99 % ee) by employing a newly evolved cyclohexylamine oxidase (CHAO) variant Y321I/M226T exhibiting catalytic efficiency that was 30 times higher than that of the wildtype CHAO. Interestingly, CHAO and its variants showed opposite enantioselectivity for Valine ethyl ester and phenylalanine ethyl ester.
