2-Ketoglutarate as a possible regulatory metabolite involved in cyclic AMP-dependent catabolite repression in Escherichia coli K12

Daniel, Jacques; Danchin, Antoine

doi:10.1016/s0300-9084(86)80027-x

Cited by 18 publications

(15 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observation that both nitrogen limitation and dimethyl-ketoglutarate addition inhibit cAMP production is consistent with our finding that α-ketoglutarate acts on the PTS at EI, a site upstream of EIIA Glc . It is further consistent with an earlier report that addition of α-ketoglutarate to cultures growing on glycerol results in decreased cAMP synthesis and inhibition of catabolite-repressed gene expression, and that this effect is dependent on the presence of EIIA Glc 21 .…”

Section: Resultssupporting

confidence: 93%

α-ketoglutarate coordinates carbon and nitrogen utilization via enzyme I inhibition

et al. 2011

View full text Add to dashboard Cite

Microbes survive in a variety of nutrient environments by modulating their intracellular metabolism. Balanced growth requires coordinated uptake of carbon and nitrogen, the primary substrates for biomass production. The mechanisms that balance carbon and nitrogen uptake are, however, poorly understood. We find in Escherichia coli that a sudden increase in nitrogen availability results in an almost immediate increase in glucose uptake. The concentrations of known glycolytic intermediates and regulators, however, remain homeostatic. Instead, we find that α-ketoglutarate, which accumulates in nitrogen limitation, directly blocks glucose uptake by inhibiting Enzyme I, the first step of the phosphotransferase system (PTS). This enables rapid modulation of glycolytic flux without marked concentration changes in glycolytic intermediates by simultaneously accelerating glucose import and consumption of the terminal glycolytic intermediate phosphoenolpyruvate. Quantitative modeling shows that this previously unidentified regulatory connection is in principle sufficient to coordinate carbon and nitrogen utilization.

show abstract

Section: Resultssupporting

confidence: 93%

α-ketoglutarate coordinates carbon and nitrogen utilization via enzyme I inhibition

et al. 2011

View full text Add to dashboard Cite

show abstract

“…7). Indeed, pioneer studies showed that when 2-OG is added to E. coli cultivated in the presence of glycerol, there is a decrease in cAMP synthesis (111). A similar effect was observed by Rabinowitz and coworkers, who noted a reduction in the rate of accumulation of cAMP when a membrane-permeating 2-OG analog (dimethylketoglutarate) was added to E. coli using glycerol as a carbon source (108).…”

Section: The Carbohydrate Ptsmentioning

confidence: 54%

The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite

Huergo

Dixon

2015

Microbiol Mol Biol Rev

242

221

View full text Add to dashboard Cite

SUMMARYThe metabolite 2-oxoglutarate (also known as α-ketoglutarate, 2-ketoglutaric acid, or oxoglutaric acid) lies at the intersection between the carbon and nitrogen metabolic pathways. This compound is a key intermediate of one of the most fundamental biochemical pathways in carbon metabolism, the tricarboxylic acid (TCA) cycle. In addition, 2-oxoglutarate also acts as the major carbon skeleton for nitrogen-assimilatory reactions. Experimental data support the conclusion that intracellular levels of 2-oxoglutarate fluctuate according to nitrogen and carbon availability. This review summarizes how nature has capitalized on the ability of 2-oxoglutarate to reflect cellular nutritional status through evolution of a variety of 2-oxoglutarate-sensing regulatory proteins. The number of metabolic pathways known to be regulated by 2-oxoglutarate levels has increased significantly in recent years. The signaling properties of 2-oxoglutarate are highlighted by the fact that this metabolite regulates the synthesis of the well-established master signaling molecule, cyclic AMP (cAMP), inEscherichia coli.

show abstract

“…Dhtkd1 is essential for mitochondrial biogenesis and function maintenance [60], as it initiates the substrate-specific and irreversible stage of the overall reaction catalyzed by Ogdh [28], [29]. Ogdh is a key regulatory site within the TCA cycle, controlling the supply of reducing equivalents (NADH) to the ETC, leading to ATP production [30], [31]. In addition, this enzyme utilizes amino acids for energy production, and produces succinyl-CoA for heme biosynthesis [28].…”

Section: Discussionmentioning

confidence: 99%

Dual Mode Action of Mangiferin in Mouse Liver under High Fat Diet

Liu

Apontes

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Chronic over-nutrition is a major contributor to the spread of obesity and its related metabolic disorders. Development of therapeutics has been slow compared to the speedy increase in occurrence of these metabolic disorders. We have identified a natural compound, mangiferin (MGF) (a predominant component of the plants of Anemarrhena asphodeloides and Mangifera indica), that can protect against high fat diet (HFD) induced obesity, hyperglycemia, insulin resistance and hyperlipidemia in mice. However, the molecular mechanisms whereby MGF exerts these beneficial effects are unknown. To understand MGF mechanisms of action, we performed unbiased quantitative proteomic analysis of protein profiles in liver of mice fed with HFD utilizing 15N metabolically labeled liver proteins as internal standards. We found that out of 865 quantified proteins 87 of them were significantly differentially regulated by MGF. Among those 87 proteins, 50% of them are involved in two major processes, energy metabolism and biosynthesis of metabolites. Further classification indicated that MGF increased proteins important for mitochondrial biogenesis and oxidative activity including oxoglutarate dehydrogenase E1 (Dhtkd1) and cytochrome c oxidase subunit 6B1 (Cox6b1). Conversely, MGF reduced proteins critical for lipogenesis such as fatty acid stearoyl-CoA desaturase 1 (Scd1) and acetyl-CoA carboxylase 1 (Acac1). These mass spectrometry data were confirmed and validated by western blot assays. Together, data indicate that MGF upregulates proteins pivotal for mitochondrial bioenergetics and downregulates proteins controlling de novo lipogenesis. This novel mode of dual pharmacodynamic actions enables MGF to enhance energy expenditure and inhibit lipogenesis, and thereby correct HFD induced liver steatosis and prevent adiposity. This provides a molecular basis supporting development of MGF or its metabolites into therapeutics to treat metabolic disorders.

show abstract

2-Ketoglutarate as a possible regulatory metabolite involved in cyclic AMP-dependent catabolite repression in Escherichia coli K12

Cited by 18 publications

References 19 publications

α-ketoglutarate coordinates carbon and nitrogen utilization via enzyme I inhibition

α-ketoglutarate coordinates carbon and nitrogen utilization via enzyme I inhibition

The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite

Dual Mode Action of Mangiferin in Mouse Liver under High Fat Diet

Contact Info

Product

Resources

About