scholarly journals The distinct roles of calcium in rapid control of neuronal glycolysis and the tricarboxylic acid cycle

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Carlos Manlio Díaz-García ◽  
Dylan J Meyer ◽  
Nidhi Nathwani ◽  
Mahia Rahman ◽  
Juan Ramón Martínez-François ◽  
...  
Keyword(s):  
Energy Demand ◽  
Granule Cells ◽  
Aerobic Glycolysis ◽  
Tricarboxylic Acid Cycle ◽  
Hippocampal Slices ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Autofluorescence Imaging ◽  
Acute Hippocampal Slices ◽  
Calmodulin Signaling

When neurons engage in intense periods of activity, the consequent increase in energy demand can be met by the coordinated activation of glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. However, the trigger for glycolytic activation is unknown and the role for Ca2+ in the mitochondrial responses has been debated. Using genetically encoded fluorescent biosensors and NAD(P)H autofluorescence imaging in acute hippocampal slices, here we find that Ca2+ uptake into the mitochondria is responsible for the buildup of mitochondrial NADH, probably through Ca2+ activation of dehydrogenases in the TCA cycle. In the cytosol, we do not observe a role for the Ca2+/calmodulin signaling pathway, or AMPK, in mediating the rise in glycolytic NADH in response to acute stimulation. Aerobic glycolysis in neurons is triggered mainly by the energy demand resulting from either Na+ or Ca2+ extrusion, and in mouse dentate granule cells, Ca2+ creates the majority of this demand.

scholarly journals The distinct roles of calcium in rapid control of neuronal glycolysis and the tricarboxylic acid cycle

2020 ◽  
Author(s):  
Carlos Manlio Díaz-García ◽  
Dylan J. Meyer ◽  
Nidhi Nathwani ◽  
Mahia Rahman ◽  
Juan Ramón Martínez-François ◽  
...  
Keyword(s):  
Energy Demand ◽  
Calcium Influx ◽  
Aerobic Glycolysis ◽  
Tricarboxylic Acid Cycle ◽  
Hippocampal Slices ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Autofluorescence Imaging ◽  
Acute Hippocampal Slices ◽  
Calmodulin Signaling

ABSTRACTWhen neurons engage in intense periods of activity, the consequent increase in energy demand can be counteracted by the coordinated activation of glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. However, the trigger for glycolytic activation is unknown and the role for Ca2+ in the mitochondrial responses has been debated. Using genetically-encoded fluorescent biosensors and NAD(P)H autofluorescence imaging in acute hippocampal slices, here we find that Ca2+ uptake into the mitochondria is responsible for the buildup of mitochondrial NADH, probably through Ca2+ activation of dehydrogenases in the TCA cycle. In the cytosol, we do not observe a role for the Ca2+/calmodulin signaling pathway, or AMPK, in mediating the rise in glycolytic NADH in response to acute stimulation. Calcium, nevertheless, is a major contributor to glycolysis, although not strictly necessary. Aerobic glycolysis in neurons is triggered mainly by the energy demand resulting from either Na+ or Ca2+ extrusion.Impact StatementWhen neurons are stimulated, calcium influx instructs mitochondria to increase energy metabolism, but it is increased energy demand in cytosol rather than Ca2+ signaling that leads to increased neuronal glycolysis.

scholarly journals HISTOCHEMICAL INVESTIGATIONS ON THE IN VIVO EFFECTS OF FLUORIDE ON TRICARBOXYLIC ACID CYCLE DEHYDROGENASES FROM PELARGONIUM ZONALE: PART II

1967 ◽  
Vol 15 (4) ◽  
pp. 202-206
Author(s):  
C. JAMES LOVELACE ◽  
GENE W. MILLER
Keyword(s):  
Sodium Fluoride ◽  
Reductase Activity ◽  
Tricarboxylic Acid Cycle ◽  
Leaf Tissue ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Pelargonium Zonale ◽  
Acid Cycle ◽  
In Vivo Effects

In vivo effects of fluoride on tricarboxylic acid (TCA) cycle dehydrogenase enzymes of Pelargonium zonale were studied using p-nitro blue tetrazoleum chloride. Plants were exposed to 17 ppb HF, and enzyme activities in treated plants were compared to those in controls. Leaves of control plants were incubated in 5 x 10–3 M sodium fluoride. Injuries observed in fumigation and solution experiments were similar. Leaf tissue subjected to HF or sodium fluoride evidenced less succinic p-nitro blue tetrazoleum reductase activity than did control tissue. Other TCA cycle dehydrogenase enzymes were not observably affected by the fluoride concentrations used in these experiments. Excised leaves cultured in 5 x 10–3 M sodium fluoride exhibited less succinic p-nitro blue tetrazoleum reductase activity after 24 hr than did leaves cultured in 5 x 10–3 M sodium chloride.

scholarly journals Current Advances in the Biodegradation and Bioconversion of Polyethylene Terephthalate

2021 ◽  
Vol 10 (1) ◽  
pp. 39
Author(s):  
Xinhua Qi ◽  
Wenlong Yan ◽  
Zhibei Cao ◽  
Mingzhu Ding ◽  
Yingjin Yuan
Keyword(s):  
Polyethylene Terephthalate ◽  
Microbial Consortium ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Microbial Consortia ◽  
Plastic Pollution ◽  
One Step ◽  
Complex Polymers ◽  
The One

Polyethylene terephthalate (PET) is a widely used plastic that is polymerized by terephthalic acid (TPA) and ethylene glycol (EG). In recent years, PET biodegradation and bioconversion have become important in solving environmental plastic pollution. More and more PET hydrolases have been discovered and modified, which mainly act on and degrade the ester bond of PET. The monomers, TPA and EG, can be further utilized by microorganisms, entering the tricarboxylic acid cycle (TCA cycle) or being converted into high value chemicals, and finally realizing the biodegradation and bioconversion of PET. Based on synthetic biology and metabolic engineering strategies, this review summarizes the current advances in the modified PET hydrolases, engineered microbial chassis in degrading PET, bioconversion pathways of PET monomers, and artificial microbial consortia in PET biodegradation and bioconversion. Artificial microbial consortium provides novel ideas for the biodegradation and bioconversion of PET or other complex polymers. It is helpful to realize the one-step bioconversion of PET into high value chemicals.

scholarly journals Association of the malate dehydrogenase-citrate synthase metabolon is modulated by intermediates of the Krebs tricarboxylic acid cycle

2021 ◽  
Author(s):  
Joy Omini ◽  
Izabela Wojciechowska ◽  
Aleksandra Skirycz ◽  
Hideaki Moriyama ◽  
Toshihiro Obata
Keyword(s):  
Malate Dehydrogenase ◽  
Metabolic Flux ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Feedback Regulation ◽  
Dynamic Structure ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Enzyme Complex ◽  
Acetyl Coa

Mitochondrial malate dehydrogenase (MDH)-citrate synthase (CS) multi-enzyme complex is a part of the Krebs tricarboxylic acid (TCA) cycle 'metabolon' which is enzyme machinery catalyzing sequential reactions without diffusion of reaction intermediates into a bulk matrix. This complex is assumed to be a dynamic structure involved in the regulation of the cycle by enhancing metabolic flux. Microscale Thermophoresis analysis of the porcine heart MDH-CS complex revealed that substrates of the MDH and CS reactions, NAD+ and acetyl-CoA, enhance complex association while products of the reactions, NADH and citrate, weaken the affinity of the complex. Oxaloacetate enhanced the interaction only when it was presented together with acetyl-CoA. Structural modeling using published CS structures suggested that the binding of these substrates can stabilize the closed format of CS which favors the MDH-CS association. Two other TCA cycle intermediates, ATP, and low pH also enhanced the association of the complex. These results suggest that dynamic formation of the MDH-CS multi-enzyme complex is modulated by metabolic factors responding to respiratory metabolism, and it may function in the feedback regulation of the cycle and adjacent metabolic pathways.

scholarly journals Staphylococcus epidermidis Polysaccharide Intercellular Adhesin Production Significantly Increases during Tricarboxylic Acid Cycle Stress

2005 ◽  
Vol 187 (9) ◽  
pp. 2967-2973 ◽  
Author(s):  
Cuong Vuong ◽  
Joshua B. Kidder ◽  
Erik R. Jacobson ◽  
Michael Otto ◽  
Richard A. Proctor ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Redox Status ◽  
Tricarboxylic Acid ◽  
Polysaccharide Intercellular Adhesin ◽  
Low Oxygen ◽  
Acid Cycle ◽  
The Tca Cycle ◽  
High Concentrations

ABSTRACT Staphylococcal polysaccharide intercellular adhesin (PIA) is important for the development of a mature biofilm. PIA production is increased during growth in a nutrient-replete or iron-limited medium and under conditions of low oxygen availability. Additionally, stress-inducing stimuli such as heat, ethanol, and high concentrations of salt increase the production of PIA. These same environmental conditions are known to repress tricarboxylic acid (TCA) cycle activity, leading us to hypothesize that altering TCA cycle activity would affect PIA production. Culturing Staphylococcus epidermidis with a low concentration of the TCA cycle inhibitor fluorocitrate dramatically increased PIA production without impairing glucose catabolism, the growth rate, or the growth yields. These data lead us to speculate that one mechanism by which staphylococci perceive external environmental change is through alterations in TCA cycle activity leading to changes in the intracellular levels of biosynthetic intermediates, ATP, or the redox status of the cell. These changes in the metabolic status of the bacteria result in the attenuation or augmentation of PIA production.

scholarly journals Neuronal control of astrocytic respiration through a variant of the Crabtree effect

2018 ◽  
Vol 115 (7) ◽  
pp. 1623-1628 ◽  
Author(s):  
Ignacio Fernández-Moncada ◽  
Iván Ruminot ◽  
Daniel Robles-Maldonado ◽  
Karin Alegría ◽  
Joachim W. Deitmer ◽  
...  
Keyword(s):  
Energy Demand ◽  
Aerobic Glycolysis ◽  
Hippocampal Slices ◽  
Energetic Efficiency ◽  
Crabtree Effect ◽  
Proliferating Cells ◽  
Neuronal Control ◽  
Synaptic Formation ◽  
Oxygen Measurements

Aerobic glycolysis is a phenomenon that in the long term contributes to synaptic formation and growth, is reduced by normal aging, and correlates with amyloid beta deposition. Aerobic glycolysis starts within seconds of neural activity and it is not obvious why energetic efficiency should be compromised precisely when energy demand is highest. Using genetically encoded FRET nanosensors and real-time oxygen measurements in culture and in hippocampal slices, we show here that astrocytes respond to physiological extracellular K+ with an acute rise in cytosolic ATP and a parallel inhibition of oxygen consumption, explained by glycolytic stimulation via the Na+-bicarbonate cotransporter NBCe1. This control of mitochondrial respiration via glycolysis modulation is reminiscent of a phenomenon previously described in proliferating cells, known as the Crabtree effect. Fast brain aerobic glycolysis may be interpreted as a strategy whereby neurons manipulate neighboring astrocytes to obtain oxygen, thus maximizing information processing.

Tricarboxylic acid cycle intermediates in human muscle at rest and during prolonged cycling

1997 ◽  
Vol 272 (2) ◽  
pp. E239-E244 ◽  
Author(s):  
M. J. Gibala ◽  
M. A. Tarnopolsky ◽  
T. E. Graham
Keyword(s):  
Fiber Type ◽  
Tricarboxylic Acid Cycle ◽  
Vastus Lateralis ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Human Muscle ◽  
Pool Size ◽  
Recruitment Pattern ◽  
Total Pool ◽  
Tca Cycle Intermediates

Previous studies have used the muscle concentration of citrate + malate + fumarate to estimate tricarboxylic acid (TCA) cycle pool size in humans [e.g., Am. J. Physiol. 259 (Cell Physiol. 28): C834-C841, 1990]. Our purpose was to quantify changes in individual TCA cycle intermediates (TCAI) and total pool size by measuring the concentrations of the eight TCAI in human muscle. Eight males cycled to exhaustion (Exh) at approximately 70% of their maximal oxygen uptake, and biopsies were obtained from the vastus lateralis at rest and during exercise. Succinyl-CoA was not consistently detectable, but the sum of the other seven TCAI was 1.23 +/- 0.04 mmol/kg dry wt at rest, 4.80 +/- 0.25 and 4.87 +/- 0.30 mmol/kg after 5 and 15 min of exercise, respectively, and 3.08 +/- 0.15 mmol/kg at Exh. Pool size during exercise was approximately 50% higher than that seen in rodent muscle after intense electrical stimulation (Eur. J. Biochem. 110: 371-377, 1980). Relative changes in individual TCAI were not uniform, and no one intermediate was "representative" of the changes in total pool size. We conclude that changes in specific intermediates or total pool size cannot be used as indicators of cycle flux and that the apparent species differences in total pool size may reflect differences in fiber type composition, recruitment pattern, or relative intensity of contraction.

scholarly journals Metabolic engineering of Bacillus amyloliquefaciens for enhanced production of S-adenosylmethionine by coupling of an engineered S-adenosylmethionine pathway and the tricarboxylic acid cycle

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Liying Ruan ◽  
Lu Li ◽  
Dian Zou ◽  
Cong Jiang ◽  
Zhiyou Wen ◽  
...  
Keyword(s):  
Metabolic Engineering ◽  
Bacillus Amyloliquefaciens ◽  
Tricarboxylic Acid Cycle ◽  
Fold Increase ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Scale Production ◽  
Free Medium ◽  
Enhanced Production ◽  
The Tca Cycle

Abstract Background S-Adenosylmethionine (SAM) is a critical cofactor involved in many biochemical reactions. However, the low fermentation titer of SAM in methionine-free medium hampers commercial-scale production. The SAM synthesis pathway is specially related to the tricarboxylic acid (TCA) cycle in Bacillus amyloliquefaciens. Therefore, the SAM synthesis pathway was engineered and coupled with the TCA cycle in B. amyloliquefaciens to improve SAM production in methionine-free medium. Results Four genes were found to significantly affect SAM production, including SAM2 from Saccharomyces cerevisiae, metA and metB from Escherichia coli, and native mccA. These four genes were combined to engineer the SAM pathway, resulting in a 1.42-fold increase in SAM titer using recombinant strain HSAM1. The engineered SAM pathway was subsequently coupled with the TCA cycle through deletion of succinyl-CoA synthetase gene sucC, and the resulted HSAM2 mutant produced a maximum SAM titer of 107.47 mg/L, representing a 0.59-fold increase over HSAM1. Expression of SAM2 in this strain via a recombinant plasmid resulted in strain HSAM3 that produced 648.99 mg/L SAM following semi-continuous flask batch fermentation, a much higher yield than previously reported for methionine-free medium. Conclusions This study reports an efficient strategy for improving SAM production that can also be applied for generation of SAM cofactors supporting group transfer reactions, which could benefit metabolic engineering, chemical biology and synthetic biology.

Metabolism of glucose-14C, pyruvate-14C, and mannitol-14C by Melampsora lini. II. Conversion to soluble products

1968 ◽  
Vol 46 (4) ◽  
pp. 453-460 ◽  
Author(s):  
D. Mitchell ◽  
Michael Shaw
Keyword(s):  
Pentose Phosphate Pathway ◽  
Tricarboxylic Acid Cycle ◽  
Rust Fungus ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Pentose Phosphate ◽  
Soluble Carbohydrates ◽  
Melampsora Lini ◽  
Carbohydrate Fraction ◽  
The Tca Cycle

Mycelium of the flax rust fungus (Melampsora lini (Pers.) Lév.), grown on flax cotyledons in tissue culture, had a mean [Formula: see text]of 4.1 and a mean C6/C1 ratio of 0.14, measured after 4 hours in radioactive glucose. The C6/C1 ratio increased with time and also after treatment with 10−5 M 2,4-dinitrophenol. The relative labelling of the (80%) ethanol-soluble carbohydrates, and organic and amino acid fractions after incubation with glucose-1-, -2-, or -6-14C also indicated preferential release of C1 as 14CO2. Trehalose (unknown A) was tentatively identified in the carbohydrate fraction and was mildly radioactive after incubation of the mycelium with labelled glucose for 3 hours. The principal radioactive products of glucose in this fraction were two unknowns, B and C, which were tentatively identified as mannitol and arabitol. The labelling patterns were consistent with their formation from intermediates of the pentose phosphate pathway. The distribution of radioactivity derived from glucose in alanine, glutamate, and aspartate also indicated that hexose or triose units formed in the pentose phosphate pathway were converted to pyruvate, which either gave rise to alanine or was further oxidized in the tricarboxylic acid cycle. Incubation with pyruvate-1-, -2-, or -3-14C for 3 hours gave rise to 14CO2 and labelled alanine, glutamate, and aspartate in a manner consistent with the operation of the TCA cycle. Mannitol-1-6-14C was not metabolized to any appreciable extent in this period, but did give rise to 14CO2 and to several unidentified compounds in the carbohydrate fraction.

scholarly journals Host nutrient milieu drives an essential role for aspartate biosynthesis during invasiveStaphylococcus aureusinfection

2020 ◽  
Vol 117 (22) ◽  
pp. 12394-12401 ◽  
Author(s):  
Aimee D. Potter ◽  
Casey E. Butrico ◽  
Caleb A. Ford ◽  
Jacob M. Curry ◽  
Irina A. Trenary ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Aerobic Glycolysis ◽  
Bacterial Pathogen ◽  
Tca Cycle ◽  
Acid Synthesis ◽  
Tricarboxylic Acid ◽  
Staphylococcal Infection ◽  
Amino Acid Synthesis ◽  
The Tca Cycle ◽  
Host Tissues

The bacterial pathogenStaphylococcus aureusis capable of infecting a broad spectrum of host tissues, in part due to flexibility of metabolic programs.S. aureus, like all organisms, requires essential biosynthetic intermediates to synthesize macromolecules. We therefore sought to determine the metabolic pathways contributing to synthesis of essential precursors during invasiveS. aureusinfection. We focused specifically on staphylococcal infection of bone, one of the most common sites of invasiveS. aureusinfection and a unique environment characterized by dynamic substrate accessibility, infection-induced hypoxia, and a metabolic profile skewed toward aerobic glycolysis. Using a murine model of osteomyelitis, we examined survival ofS. aureusmutants deficient in central metabolic pathways, including glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, and amino acid synthesis/catabolism. Despite the high glycolytic demand of skeletal cells, we discovered thatS. aureusrequires glycolysis for survival in bone. Furthermore, the TCA cycle is dispensable for survival during osteomyelitis, andS. aureusinstead has a critical need for anaplerosis. Bacterial synthesis of aspartate in particular is absolutely essential for staphylococcal survival in bone, despite the presence of an aspartate transporter, which we identified as GltT and confirmed biochemically. This dependence on endogenous aspartate synthesis derives from the presence of excess glutamate in infected tissue, which inhibits aspartate acquisition byS. aureus. Together, these data elucidate the metabolic pathways required for staphylococcal infection within bone and demonstrate that the host nutrient milieu can determine essentiality of bacterial nutrient biosynthesis pathways despite the presence of dedicated transporters.

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