Alpha-ketoglutarate as an intermediate in glutamate metabolism by Peptococcus aerogenes

1972 ◽  
Vol 18 (6) ◽  
pp. 875-880 ◽  
Author(s):  
W. M. Johnson ◽  
D. W. S. Westlake
Keyword(s):  
Potential Energy ◽  
Glutamic Acid ◽  
Tca Cycle ◽  
The Other ◽  
Glutamate Metabolism ◽  
Fermentation Products ◽  
Acid Dehydrogenase ◽  
Specific Distribution ◽  
The Tca Cycle ◽  
Hydroxyglutaric Acid

The pathway from glutamic acid to α-hydroxyglutaric acid in Peptococcus aerogenes proceeds via α-ketoglutaric acid and is mediated by two NAD-dependent enzymes. One enzyme, an NAD-dependent glutamic acid dehydrogenase, oxidatively deaminates glutamic acid to α-ketoglutaric acid. The other enzyme, α-ketoglutaric acid reductase, reduces α-ketoglutaric acid to α-hydroxyglutaric acid in the presence of NADH. The demonstration of a very low level of α-ketoglutaric acid dehydrogenase activity in crude cell-free extracts indicates that the primary metabolic pathway for glutamic acid carbons proceeds via α-hydroxyglutaric acid and not via the TCA cycle. Potential energy-yielding mechanisms are discussed relative to the known specific distribution of glutamic acid carbon atoms in fermentation products.

Purification and characterization of glutamic acid dehydrogenase and α-ketoglutaric acid reductase from Peptococcus aerogenes

1972 ◽  
Vol 18 (6) ◽  
pp. 881-892 ◽  
Author(s):  
W. M. Johnson ◽  
D. W. S. Westlake
Keyword(s):  
Glutamic Acid ◽  
Kinetic Data ◽  
Acid Metabolism ◽  
The Other ◽  
Keto Acid ◽  
Glutamate Metabolism ◽  
Purification And Characterization ◽  
Acid Dehydrogenase ◽  
Acid Reduction

Two NAD-dependent enzymes involved in glutamic acid metabolism have been isolated from cell-free extracts of P. aerogenes. One enzyme, glutamic acid dehydrogenase, was shown to oxidatively deaminate glutamic acid yielding α-ketoglutaric acid in the presence of NAD but not NADP. The other enzyme, an NADH-requiring α-ketoglutarate reductase, reduced the α-keto acid to α-hydroxy-glutarate. The two NAD-dependent enzymes were separated, purified, and characterized. The results indicate that glutamic acid dehydrogenase, an enzyme not frequently implicated in anaerobic glutamate metabolism, is a predominating protein in extracts of P. aerogenes grown in the presence of glutamate. Kinetic data showed that the equilibrium of the latter reaction favored the direction of keto acid reduction.

The biosynthesis of aspartic acid, glutamic acid, and alanine in Rhizobium japonicum

1971 ◽  
Vol 17 (5) ◽  
pp. 683-688 ◽  
Author(s):  
Thomas T. Lillich ◽  
Gerald H. Elkan
Keyword(s):  
Amino Acids ◽  
Glutamic Acid ◽  
Aspartic Acid ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Carbon Skeleton ◽  
The Other ◽  
Rhizobium Japonicum ◽  
Oxalacetic Acid ◽  
The Tca Cycle

The biosynthesis of aspartic acid and the incorporation of its carbon skeleton into glutamic acid and alanine was investigated in Rhizobium japonicum. It was found that oxalacetic acid (OAA) occupies a key position in the metabolism of this amino acid and the dissemination of its carbon skeleton into other amino acids. Aspartic acid is formed by two pathways involving the amination of OAA. In one pathway, OAA is synthesized by the tricarboxylic acid (TCA) cycle and in the other by the carboxylation of either pyruvate or phosphoenolpyruvate. The carbon skeleton of aspartic acid can be incorporated into alanine either by deamination to OAA followed by decarboxylation to pyruvate and reamination or directly by decarboxylation of the number four carbon. There are at least two pathways by which aspartic acid carbon is incorporated into glutamic acid. One path involves the synthesis of α-ketoglutarate from OAA via the TCA cycle, the other is a condensation yielding either β-methylaspartate or α-ketoglutarate, which is then converted to glutamate.

Memorialization: A Learned Skill or an Inborn Talent?

2001 ◽  
Vol 16 (3) ◽  
pp. 83-84
Author(s):  
Alice G Brandfonbrener
Keyword(s):  
Medical School ◽  
Brachial Plexus ◽  
Tca Cycle ◽  
The Other ◽  
Sight Reading ◽  
Other Hand ◽  
The Tca Cycle ◽  
Great Ease

Although it is often said that we tend to forget unhappy memories, many linger on. For instance, how well I recall what was for me an agony during medical school of memorizing the TCA cycle, the brachial plexus, and the bones of the wrist! I somehow dealt with it at the time, but ask me to repeat them now and I couldn’t begin to do it. On the other hand, it is true that I can still recall a few bars of Mozart sonatas I learned when I was even younger, but I’d fare much better sitting down and sight-reading the same previously memorized works. It has always been frustrating for me to recognize and accept that, long before I attained my current age, memorizing was not one of my strong points, especially compared with some of my colleagues who seemingly did it with great ease and even satisfaction. Ease of memorization appears to be in part an innate skill and, I’m sure, like other such skills, can be enhanced by training. There is also selective memory. Like many of my medical colleagues I can predictably recall a given patient’s pathology but much less readily his or her name. Lucky for us that we went into medicine and not into politics!

scholarly journals Toward an Understanding Of the Structural and Mechanistic Aspects of Protein-Protein Interactions in 2-Oxo Acid Dehydrogenase Complexes

2021 ◽  
Author(s):  
Natalia S. Nemeria ◽  
Xu Zhang ◽  
Joao Leandro ◽  
Jieyu Zhou ◽  
Luying Yang ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Tca Cycle ◽  
Degradation Pathway ◽  
Protein Protein Interactions ◽  
Acid Dehydrogenase ◽  
The Tca Cycle ◽  
Hybrid Complex ◽  
Key Enzyme ◽  
Lysine Degradation ◽  
Dehydrogenase Complex

The 2-oxoglutarate dehydrogenase complex (OGDHc) is a key enzyme in the TCA cycle and represents one of the major regulators of mitochondrial metabolism through NADH and reactive oxygen species levels. The OGDHc impacts cell metabolic and cell signaling pathways through the coupling of 2-oxoglutarate metabolism to gene transcription related to tumor cell proliferation and aging. DHTKD1 is a gene encoding 2-oxoadipate dehydrogenase (E1a), which functions in the L-lysine degradation pathway. The potentially damaging variants in DHTKD1 have been associated to the (neuro) pathogenesis of several diseases. Evidence was obtained for the formation of a hybrid complex between the OGDHc and E1a, suggesting a potential cross talk between the two metabolic pathways and raising fundamental questions about their assembly. Here we reviewed the recent findings and advances in understanding of protein-protein interactions in OGDHc and 2-oxoadipate dehydrogenase complex (OADHc), an understanding that will create a scaffold to help design approaches to mitigate the effects of diseases associated with dysfunction of the TCA cycle or lysine degradation. A combination of biochemical, biophysical and structural approaches such as chemical cross-linking MS and cryo-EM appears particularly promising to provide vital information for the assembly of 2-oxo acid dehydrogenase complexes, their function and regulation.

THE BIOSYNTHESIS OF SOME AMINO ACIDS IN PENICILLIUM DIGITATUM

1958 ◽  
Vol 4 (6) ◽  
pp. 627-632 ◽  
Author(s):  
Donald J. Reed ◽  
Vernon H. Cheldelin ◽  
Chih H. Wang
Keyword(s):  
Amino Acids ◽  
Glutamic Acid ◽  
Aspartic Acid ◽  
Carbon Sources ◽  
Tca Cycle ◽  
Penicillium Digitatum ◽  
Tracer Techniques ◽  
The Tca Cycle

The pathways of biosynthesis of alanine, serine, glycine, aspartic acid, and glutamic acid in Penicillium digitntum have been studied by means of tracer techniques, using glucose-2-C14 and glucose-6-C11 as carbon sources. Alanine appears to be derived directly from pyruvate formed in the glycolytic degradation of glucose. Serine is synthesized from glycine, which is in turn derived mainly from a C2 fragment that originates in the C2–C3 cleavage of pentose, a product of phosphogluconate decarboxylation. The biosynthesis of aspartic acid in this organism may involve several pathways. Glutamic acid appears to be synthesized from glucose intermediates via the conventional reactions of the TCA cycle.

scholarly journals Synergistic Effect of Saikosaponin a and Albiflorin Against Corticosterone-Induced Neuro-Injury in PC12 Cells via Regulation of TCA Cycle, Purine Metabolism, and Glutamate Metabolism

2021 ◽  
Author(s):  
Xiao Li ◽  
Ruihong Hou ◽  
Hao Shi ◽  
Xuemei Qin ◽  
Yanfei Wu ◽  
...  
Keyword(s):  
Neuroprotective Effect ◽  
Tca Cycle ◽  
Purine Metabolism ◽  
Glutamate Metabolism ◽  
Metabolism Disorder ◽  
The Tca Cycle ◽  
Synergistic Mechanism ◽  
Radix Bupleuri ◽  
Radix Paeoniae Alba ◽  
Saikosaponin A

Abstract The combination of Radix Bupleuri - Radix Paeoniae alba is one of the most approbated herb pairs in traditional Chinese medicine (TCM) formula for curing depression. Saikosaponin A (SSA) and albiflorin (AF) are major bioactive compounds of Radix Bupleuri and Radix Paeoniae alba respectively, which possess antidepressant effects in pharmacological experiments. However, whether SSA and AF have synergistic neuroprotective effects and the synergistic mechanism is still unknown. The present study employed the corticosterone-induced PC12 cells neuro-injury model to assess the protective effect of SSA and AF, alone and in combination, and the synergistic effect was analyzed using three mathematical models. Meanwhile, the cell metabolomics was used to detect the effects on metabolite regulation of SSA and AF, alone and in combination. According to the results of cell metabolomics, the vital cell transduction pathway related to the crucial cell metabolic pathways were selected. Furthermore, the key metabolites, metabolic enzymes, and cellular markers were verified by ELISA and Western blotting. The results showed that the combination of SSA and AF has a synergistic neuroprotective effect. Besides, the combination could regulate more metabolites (16) than a single agent (12 & 10) and possessed a stronger adjustment effect on metabolites. Correspondingly, the combination regulated more metabolism pathways (7) than alone agents (3 & 5). Furthermore, the TCA cycle, purine metabolism, and glutamate metabolism were selected as crucial metabolism pathways. The results showed that the TCA cycle disorder was regulated by SSA and AF via improving mitochondrial function. The purine metabolism disorder was regulated by SSA via inhibition xanthine oxidase (XOD) activity and the glutamate metabolism disorder was regulated by AF via inhibition glutaminase (GLS) activity. Moreover, the oxidative stress induced by the purine metabolism disorder was attenuated by SSA via a reduction in the ROS level. Additionally, the inflammation induced by the oxidative stress was attenuated by the SSA and AF via inhibition of the NLRP3 protein expression. This study for the first time demonstrated the synergistic neuroprotective effect of SSA and AF, and the synergistic mechanism was involved in metabolic disorders regulation.

scholarly journals Glutamate-glutamine homeostasis is perturbed in neurons and astrocytes derived from patient iPSC models of frontotemporal dementia

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Blanca I. Aldana ◽  
Yu Zhang ◽  
Pia Jensen ◽  
Abinaya Chandrasekaran ◽  
Sofie K. Christensen ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Stem Cells ◽  
Energy Metabolism ◽  
Frontotemporal Dementia ◽  
Pluripotent Stem Cells ◽  
Quantitative Proteomics ◽  
Tca Cycle ◽  
Glutamate Metabolism ◽  
The Tca Cycle ◽  
Molecular Determinants

Abstract Frontotemporal dementia (FTD) is amongst the most prevalent early onset dementias and even though it is clinically, pathologically and genetically heterogeneous, a crucial involvement of metabolic perturbations in FTD pathology is being recognized. However, changes in metabolism at the cellular level, implicated in FTD and in neurodegeneration in general, are still poorly understood. Here we generate induced human pluripotent stem cells (hiPSCs) from patients carrying mutations in CHMP2B (FTD3) and isogenic controls generated via CRISPR/Cas9 gene editing with subsequent neuronal and glial differentiation and characterization. FTD3 neurons show a dysregulation of glutamate-glutamine related metabolic pathways mapped by 13C-labelling coupled to mass spectrometry. FTD3 astrocytes show increased uptake of glutamate whilst glutamate metabolism is largely maintained. Using quantitative proteomics and live-cell metabolic analyses, we elucidate molecular determinants and functional alterations of neuronal and glial energy metabolism in FTD3. Importantly, correction of the mutations rescues such pathological phenotypes. Notably, these findings implicate dysregulation of key enzymes crucial for glutamate-glutamine homeostasis in FTD3 pathogenesis which may underlie vulnerability to neurodegeneration. Graphical abstract Neurons derived from human induced pluripotent stem cells (hiPSCs) of patients carrying mutations in CHMP2B (FTD3) display major metabolic alterations compared to CRISPR/Cas9 generated isogenic controls. Using quantitative proteomics, 13C-labelling coupled to mass spectrometry metabolic mapping and seahorse analyses, molecular determinants and functional alterations of neuronal and astrocytic energy metabolism in FTD3 were characterized. Our findings implicate dysregulation of glutamate-glutamine homeostasis in FTD3 pathogenesis. In addition, FTD3 neurons recapitulate glucose hypometabolism observed in FTD patient brains. The impaired mitochondria function found here is concordant with disturbed TCA cycle activity and decreased glycolysis in FTD3 neurons. FTD3 neuronal glutamine hypermetabolism is associated with up-regulation of PAG expression and, possibly, ROS production. Distinct compartments of glutamate metabolism can be suggested for the FTD3 neurons. Endogenous glutamate generated from glutamine via PAG may enter the TCA cycle via AAT (left side of neuron) while exogenous glutamate taken up from the extracellular space may be incorporated into the TCA cycle via GDH (right side of the neuron) FTD3 astrocytic glutamate uptake is upregulated whilst glutamate metabolism is largely maintained. Finally, pharmacological reversal of glutamate hypometabolism manifesting from decreased GDH expression should be explored as a novel therapeutic intervention for treating FTD3.

Liquid-liquid extraction of succinate using a dicopper cryptate

2020 ◽  
Author(s):  
Riccardo Mobili ◽  
Sonia La Cognata ◽  
Francesca Merlo ◽  
Andrea Speltini ◽  
Massimo Boiocchi ◽  
...  
Keyword(s):  
Aqueous Phase ◽  
Visible Spectrum ◽  
Tca Cycle ◽  
Residual Concentration ◽  
Waste Products ◽  
Liquid Liquid Extraction ◽  
The Tca Cycle ◽  
Quantitative Extraction ◽  
Uv Visible

<div> <p>The extraction of the succinate dianion from a neutral aqueous solution into dichloromethane is obtained using a lipophilic cage-like dicopper(II) complex as the extractant. The quantitative extraction exploits the high affinity of the succinate anion for the cavity of the azacryptate. The anion is effectively transferred from the aqueous phase, buffered at pH 7 with HEPES, into dichloromethane. A 1:1 extractant:anion adduct is obtained. Extraction can be easily monitored by following changes in the UV-visible spectrum of the dicopper complex in dichloromethane, and by measuring the residual concentration of succinate in the aqueous phase by HPLC−UV. Considering i) the relevance of polycarboxylates in biochemistry, as e.g. normal intermediates of the TCA cycle, ii) the relevance of dicarboxylates in the environmental field, as e.g. waste products of industrial processes, and iii) the recently discovered role of succinate and other dicarboxylates in pathophysiological processes including cancer, our results open new perspectives for research in all contexts where selective recognition, trapping and extraction of polycarboxylates is required. </p> </div>

Effect of cations on the activity of L-glutamic acid dehydrogenase

Life Sciences ◽  
1963 ◽  
Vol 2 (11) ◽  
pp. 834-839 ◽  
Author(s):  
E. Schoffeniels ◽  
R. Gilles
Keyword(s):  
Glutamic Acid ◽  
Acid Dehydrogenase
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