| α-Ketoglutaric acid is an organic compound with the formula H2CC(O)(CH2)2CO2H). A white, nontoxic solid, it is a common dicarboxylic acid. Relevant to its biological roles, it exists in water as its conjugate base α-ketoglutarate. It is also classified as a 2-ketocarboxylic acid. β-Ketoglutaric acid is an isomer. "Ketoglutaric acid" and "ketoglutarate", when not qualified as α or β, almost always refers respectively to α-ketoglutaric acid or α-ketoglutarate.
α-Ketoglutarate is an intermediate in the citric acid cycle, a cycle that supplies the energy to cells. It is also an intermediate in or product of several other metabolic pathways. These include its being a component of metabolic pathways that: make amino acids and in the process regulate the cellular levels of carbon, nitrogen, and ammonia; reduce the cellular levels of potentially toxic reactive oxygen species; and synthesize the neurotransmitter gamma-aminobutyric acid. It also acts as a direct stimulator of, or cofactor (i.e., required for but does not itself stimulate) for various cellular functions as defined in studies that are primarily preclinical (i.e., conducted in animal models of disease or on animal or human tissues). These studies have provided evidence that α-ketoglutarate contributes to regulating: kidney function; the benefits that resistance exercise has in reducing obesity, strengthening muscles, and preventing muscle atrophy; glucose tolerance as defined in glucose tolerance tests; aging and the development of changes that are associated with aging including old age-related disorders and diseases; the development and/or progression of certain types of cancer and inflammations; and the differentiation of immature T cells into mature T cells. |
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| InChI=1S/C5H6O5/c6-3(5(9)10)1-2-4(7)8/h1-2H2,(H,7,8)(H,9,10) |
| KPGXRSRHYNQIFN-UHFFFAOYSA-N |
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Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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fundamental metabolite
Any metabolite produced by all living cells.
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View more via ChEBI Ontology
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2-Ketoglutaric acid
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KEGG COMPOUND
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alpha-Ketoglutaric acid
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KEGG COMPOUND
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α-ketoglutaric acid
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NIST Chemistry WebBook
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Oxoglutaric acid
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KEGG COMPOUND
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1705689
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Reaxys Registry Number
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Reaxys
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328-50-7
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CAS Registry Number
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KEGG COMPOUND
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328-50-7
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CAS Registry Number
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NIST Chemistry WebBook
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328-50-7
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CAS Registry Number
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ChemIDplus
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602480
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Gmelin Registry Number
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Gmelin
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Otto C, Yovkova V, Barth G (2011)
Overproduction and secretion of α-ketoglutaric acid by microorganisms.
Applied microbiology and biotechnology 92, 689-695 [PubMed:21964641]
[show Abstract]
This mini-review presents a summary of research results of biotechnological production of alpha-ketoglutaric acid (KGA) by bacteria and yeasts. KGA is of particular industrial interest due to its broad application scope, e.g., as building block chemical for the chemical synthesis of heterocycles, dietary supplement, component of infusion solutions and wound healing compounds, or as main component of new elastomers with a wide range of interesting mechanical and chemical properties. Currently KGA is produced via different chemical pathways, which have a lot of disadvantages. As an alternative several bacteria and yeasts have already been studied for their ability to produce KGA as well as for conditions of overproduction and secretion of this intermediate of the tricarboxylic acid cycle. The aim of this mini-review was to summarize the known data and to discuss the potentials of biotechnological processes of KGA production. | Siu VM, Ratko S, Prasad AN, Prasad C, Rupar CA (2010)
Amish microcephaly: Long-term survival and biochemical characterization.
American journal of medical genetics. Part A 152A, 1747-1751 [PubMed:20583149]
[show Abstract]
Amish microcephaly (MCPHA, OMIM #607196) is a metabolic disorder that has been previously characterized by severe infantile lethal congenital microcephaly and alpha-ketoglutaric aciduria. All reported patients have been from the Pennsylvania Amish community and homozygous for a p.Gly177Ala mutation in SLC25A19. We present a further male patient with MCPHA born to distantly consanguineous parents in Ontario, Canada with Amish ancestors. Microcephaly was evident at 21 weeks gestation on ultrasound. At birth, the facial appearance and brain MRI scan were characteristic of MCPHA, with the additional features of partial agenesis of the corpus callosum and a closed spinal dysraphic state. Urine levels of alpha-ketoglutaric acid were normal at birth and during metabolic crisis, but were markedly elevated during a time of metabolic stability. A severe lactic acidosis was present during metabolic crises and responded to treatment with a high fat diet. At age 7 years, the child is healthy but has severe microcephaly and profound developmental delay. SLC25A19 has been described as a mitochondria inner membrane transporter for both deoxynucleotides and thiamine pyrophosphate (TPP). The biochemical phenotype of MCPHA may be attributable to decreased activity of the three mitochondrial enzymes that require TPP as a cofactor: pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and branched chain amino acid dehydrogenase. We confirm that alpha-ketoglutaric aciduria is not a constant finding in MCPHA and suggest that a persistent lactic acidemia may be more common. The diagnosis should be considered in patients with severe congenital microcephaly, especially in association with lissencephaly, dysgenesis of the corpus callosum, or a spinal dysraphic state. | Wagner BM, Donnarumma F, Wintersteiger R, Windischhofer W, Leis HJ (2010)
Simultaneous quantitative determination of alpha-ketoglutaric acid and 5-hydroxymethylfurfural in human plasma by gas chromatography-mass spectrometry.
Analytical and bioanalytical chemistry 396, 2629-2637 [PubMed:20155414]
[show Abstract]
Alpha-ketoglutaric acid (alpha-KG) and 5-hydroxymethylfurfural (5-HMF) are currently under investigation as promising cancer cell damaging agents. A method for the simultaneous quantitative determination of alpha-KG and 5-HMF in human plasma was established for screening these compounds in human plasma. Plasma samples were directly treated with O-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine hydrochloride to form the corresponding oximes, thus facilitating subsequent liquid-liquid extraction. After formation of the trimethylsilyl ethers, samples were analyzed by gas chromatography with electron ionization mass spectrometry. Stable isotope labeled standards were used, the preparation of (13)C(6)-5-HMF is described. Limits of quantitation were set to 0.938 microg/mL for alpha-KG and 0.156 microg/mL for 5-HMF. Inter-day accuracy was < or = 93.7% (alpha-KG) and < or = 92.8% (5-HMF). Inter-day precision was < or = 6.0% (alpha-KG) and < or = 4.6% (5-HMF). The method has been successfully applied to pharmacokinetic profiling of the compounds after intravenous application. | Edelstein PH, Edelstein MA (2010)
Comparison of the plating efficiencies and shelf lives of three different commercial buffered charcoal yeast extract media supplemented with alpha-ketoglutaric acid.
Journal of clinical microbiology 48, 1882-1883 [PubMed:20200292]
[show Abstract]
The plating efficiencies and shelf lives of locally made buffered charcoal yeast extract medium supplemented with alpha-ketoglutaric acid (BCYEalpha) were compared to those of media made by BD, Hardy, and Remel. Lung homogenates from guinea pigs infected with Legionella pneumophila were plated monthly onto different medium lots. All media performed equally well and had shelf lives of at least 12 months. | Zhou J, Zhou H, Du G, Liu L, Chen J (2010)
Screening of a thiamine-auxotrophic yeast for alpha-ketoglutaric acid overproduction.
Letters in applied microbiology 51, 264-271 [PubMed:20636327]
[show Abstract]
AimsTo obtain a thiamine-auxotrophic yeast strain that overproduces alpha-ketoglutaric acid (alpha-KG) from glycerol and to investigate nutrient effects on alpha-KG production.Methods and resultsYeast strain WSH-Z06, a thiamine auxotroph that gave high yields of alpha-KG from glycerol, was obtained by screening for ampicillin/kanamycin resistance and thiamine auxotrophy. The strain was identified as Yarrowia lipolytica based on physiological, chemical, and phylogenetic analysis. The ability of the strain to convert glycerol to alpha-KG was analysed by investigating the effects of nutritional factors, including thiamine, riboflavin, nitrogen sources, and calcium ion.ConclusionsThiamine and calcium ion concentration had the greatest effect on alpha-KG accumulation. Under optimal conditions, a yield of 39.2 g l(-1)alpha-KG was obtained from 100 g l(-1) glycerol, with 16.84 g l(-1) pyruvate as a by-product.Significance and impact of the studyThe current work provides a method for screening for an alpha-KG overproducer. Nutrients have a significant impact on alpha-KG production in the yeast strain presented here. The alpha-KG-overproducing yeast strain Y. lipolytica WSH-Z06 is a promising parent strain for further metabolic engineering to lower by-product accumulation and accelerate glycerol utilization. | Zhou YT, Nie HL, Branford-White C, He ZY, Zhu LM (2009)
Removal of Cu2+ from aqueous solution by chitosan-coated magnetic nanoparticles modified with alpha-ketoglutaric acid.
Journal of colloid and interface science 330, 29-37 [PubMed:18990406]
[show Abstract]
Chitosan-coated magnetic nanoparticles (CCMNPs), modified with a biodegradable and eco-friendly biologic reagent, alpha-ketoglutaric acid (alpha-KA), was used as a magnetic nanoadsorbent to remove toxic Cu(2+) ions from aqueous solution. The prepared magnetic nanoadsorbents were characterized by FTIR, TEM, VSM, XRD, and EDS. Factors influencing the adsorption of Cu(2+), e.g., initial metal concentration, initial pH, contact time and adsorbent concentration were investigated. TEM images show that the dimension of multidispersed circular particles is about 30 nm and no marked aggregation occurs. VSM patterns indicate superparamagnetic properties of magnetic nanoadsorbents. EDS pictures confirm the presence of the Cu(2+) on the surface of magnetic nanoadsorbents. Equilibrium studies show that Cu(2+) adsorption data follow Langmuir model. The maximum adsorption capacity (q(max)) for Cu(2+) ions was estimated to be 96.15 mg/g, which was higher than that of pure CCMNPs. The desorption data show no significant desorption hysteresis occurred. In addition, the high stability and recovery capacity of the chitosan-coated magnetic nanoparticles modified with alpha-ketoglutaric acid (alpha-KA-CCMNPs) suggest that these novel magnetic nanoadsorbents have potential applications for removing Cu(2+) from wastewater. | Castrillo JI, Zeef LA, Hoyle DC, Zhang N, Hayes A, Gardner DC, Cornell MJ, Petty J, Hakes L, Wardleworth L, Rash B, Brown M, Dunn WB, Broadhurst D, O'Donoghue K, Hester SS, Dunkley TP, Hart SR, Swainston N, Li P, Gaskell SJ, Paton NW, Lilley KS, Kell DB, Oliver SG (2007)
Growth control of the eukaryote cell: a systems biology study in yeast.
Journal of biology 6, 4 [PubMed:17439666]
[show Abstract]
BackgroundCell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking.ResultsMetabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth.ConclusionThis work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell. |
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