Metabolic alterations mediated by 2-ketobutyrate in Escherichia coli K12

Danchin, Antoine; Dondon, L.; Daniel, Jacques

doi:10.1007/bf00382086

Cited by 48 publications

(36 citation statements)

References 18 publications

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“…5C), which increases its production, and by L-valine inhibition of the AHAS I and AHAS III isozymes, which reduces its consumption. It is now known that this ␣KB accumulation is toxic to cells because of its ability to inhibit the glucose PTS transport system (24,25). Thus, as reproduced by our simulations, L-valine growth inhibition of E. coli K12 is not a consequence of L-isoleucine starvation.…”

Section: Responses To Metabolic and Genetic Perturbations L-valine Grsupporting

confidence: 65%

“…However, concomitant with the decrease in ␣KB observed in the presence of 500 M L-isoleucine, the cellular TDA in the active R state is reversed to the control level observed in the absence of L-valine. These simulations are verified by experimental results accumulated from multiple laboratories over a three decade period (6,24,25).…”

Section: Responses To Metabolic and Genetic Perturbations L-valine Grsupporting

confidence: 64%

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A Mathematical Model for the Branched Chain Amino Acid Biosynthetic Pathways of Escherichia coli K12

Yang

Shapiro

Hung

et al. 2005

Journal of Biological Chemistry

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Systems biology may be broadly defined as the integration of diverse data into useful biological models that allow scientists to easily observe complex cellular behaviors and predict the outcomes of metabolic and genetic perturbations. As a first step toward the elucidation of the systems biology of the model organism Escherichia coli, we have elected to limit our initial efforts to the development of a mathematical model for the complex but well studied metabolic pathways for the biosynthesis of the branched chain amino acids L-isoleucine, L-valine, and L-leucine.The biosynthetic pathways for the branched chain amino acids are shown in Fig. 1 (1-3). L-Threonine deaminase (TDA), 1 the first enzyme specific for the biosynthesis of L-isoleucine, is end product-inhibited by L-isoleucine, and ␣-isopropylmalate synthase (IPMS), the first enzyme specific for the biosynthesis of L-leucine, is end product-inhibited by L-leucine. However, because the parallel pathways for L-valine and L-isoleucine biosynthesis are catalyzed by a set of bi-functional enzymes that bind substrates from either pathway, L-valine inhibition of the first enzyme specific for its biosynthesis catalyzed by a single ␣-acetohydroxy acid synthase (AHAS) could compromise the cell for L-isoleucine biosynthesis or result in the accumulation of a toxic metabolic intermediate, ␣-ketobutyrate (␣KB). This type of regulatory problem is often solved by using multiple isozymes with different substrate preferences that are differentially regulated by multiple end products of parallel pathways. In this case, there are three AHAS isozymes that catalyze the first step of the L-valine and the second step of the L-isoleucine pathway (4). AHAS I has substrate preferences for the condensation of two pyruvate molecules required for Lvaline biosynthesis and is end product-inhibited by L-valine (4). AHAS III shows no preference for pyruvate or ␣KB. Although this isozyme can produce intermediates for both L-valine and L-isoleucine, it is inhibited by L-valine (4). The AHAS II isozyme has substrate preferences for the condensation of pyruvate and the ␣KB required for L-isoleucine biosynthesis, and it is not inhibited by any of the branched chain amino acids (4). However, AHAS II is not active in the E. coli. K12 strain (5). Consequently, this strain cannot grow in the presence of high levels of L-valine unless L-isoleucine is also added to the growth medium (6).TDA is an allosteric enzyme whose kinetic behavior can be described by the concerted allosteric transition mode of the Monod, Wyman, and Changeux (MWC) model (7,8). According to the MWC model, TDA can exist in an active state (R) or an inactive state (T) (8, 9). The fraction of active enzyme in the R or T states is determined by the concentrations and relative affinities of the substrate (L-threonine), the inhibitor (L-isoleucine), and the activator (L-valine) for the R and T states.

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Section: Responses To Metabolic and Genetic Perturbations L-valine Grsupporting

confidence: 65%

Section: Responses To Metabolic and Genetic Perturbations L-valine Grsupporting

confidence: 64%

A Mathematical Model for the Branched Chain Amino Acid Biosynthetic Pathways of Escherichia coli K12

Yang

Shapiro

Hung

et al. 2005

Journal of Biological Chemistry

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“…Using these values and the known calculated values of E. coli for cell volume (BNID 100004), protein concentration (BNID 108263), and the frequency of lysines present in E. coli (BNID 100636) (13), we estimated the amount of acetate on protein to be between 1.7 and 2.8 mM. This is striking because the concentration of acetyl-CoA is estimated to be less than 500 M in E. coli (15). This analysis reveals the high amount of acetate stored on proteins, although future experiments will be needed to assess the turnover rate with respect to acetyl-CoA and acetyl phosphate consumption.…”

Section: Discussionmentioning

confidence: 97%

“…Recently, acetyl proteome measurements have utilized labeling strategies, such as tandem mass tags or stable isotope labeling by amino acids in cell culture, followed by immunoenrichment of acetylated peptides and mass spectrometry (8,(12)(13)(14)(15). Although these approaches are valuable for comparing relative changes across conditions, they do not provide direct information on stoichiometry at individual sites (1,14).…”

mentioning

confidence: 99%

Stoichiometry of Site-specific Lysine Acetylation in an Entire Proteome

Baeza

Dowell

Smallegan

et al. 2014

Journal of Biological Chemistry

143

172

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Background: Lysine acetylation sites have been mapped, but information on stoichiometry is lagging. Results: We developed and utilized the first direct, unbiased method for quantifying site-specific acetylation stoichiometry of a proteome without antibody enrichment. Conclusion: High stoichiometry is associated with central metabolism, transcription, and translation. Loss of deacetylase CobB affects site-specific and global acetylation stoichiometry, altering acetyl-CoA metabolism. Significance: Stoichiometry provides functional insight into protein acetylation.

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“…Exogenously added AKB is toxic to S. typhimurium (25,28), although the precise nature of toxicity is unclear. It has been proposed that AKB interferes with valine biosynthesis (28), formation of valyl-tRNAval and isoleucyl-tRNAIle (30), pantothenate biosynthesis (25), pts-mediated sugar transport (9,10), flux to and through the tricarboxylic acid cycle (8), and formation of aspartate (9). It has also been suggested that AKB functions as an alarmone which signals a shift from an anaerobic environment to an aerobic environment (9).…”

mentioning

confidence: 99%

Sensitivity of a Salmonella typhimurium aspC mutant to sulfometuron methyl, a potent inhibitor of acetolactate synthase II

Dyk¹,

LaRossa²

1986

J Bacteriol

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Sulfometuron methyl is a potent and specific inhibitor of acetolactate synthase II in Salmonella typhimurium.Mutant strains sensitive to sulfometuron methyl on minimal medium were isolated following mutagenesis with TnlO. A conditionally auxotrophic insertion mutant, strain SMS409, which required aspartate at high temperatures or in the presence of tyrosine, was found among the 15 mutants isolated. The TnWO insertion in strain SMS409 was mapped by conjugation and transduction to the region between aroA and pncB at 20 min on the chromosome of S. typhimurium; this location is similar to the genetic location of aspC in Escherichia coli.The specific activity of the aspC product, aspartate aminotransferase, was severely reduced in strain SMS409. This indicated that the TnlO insertion in strain SMS409 inactivated aspC. An aspC mutant of E. coli was also inhibited by either sulfometuron methyl or tyrosine. We present a hypothesis which relates the observed a-ketobutyrate accumulation in sulfometuron methyl-inhibited cultures of strain SMS409 to aspartate starvation.

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Metabolic alterations mediated by 2-ketobutyrate in Escherichia coli K12

Cited by 48 publications

References 18 publications

A Mathematical Model for the Branched Chain Amino Acid Biosynthetic Pathways of Escherichia coli K12

A Mathematical Model for the Branched Chain Amino Acid Biosynthetic Pathways of Escherichia coli K12

Stoichiometry of Site-specific Lysine Acetylation in an Entire Proteome

Sensitivity of a Salmonella typhimurium aspC mutant to sulfometuron methyl, a potent inhibitor of acetolactate synthase II

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