scholarly journals Glycolysis versus TCA Cycle in the Primate Brain as Measured by Combining 18F-FDG PET and 13C-NMR

2005 ◽  
Vol 25 (11) ◽  
pp. 1418-1423 ◽  
Author(s):  
Fawzi Boumezbeur ◽  
Laurent Besret ◽  
Julien Valette ◽  
Marie-Claude Gregoire ◽  
Thierry Delzescaux ◽  
...  
Keyword(s):  
Tca Cycle ◽  
Glycolytic Flux ◽  
Cerebral Metabolic Rate ◽  
Metabolic Coupling ◽  
Primate Brain ◽  
Positron Emission ◽  
The Tca Cycle ◽  
The Brain ◽  
Good Agreement ◽  
C Nmr

The glycolytic flux (cerebral metabolic rate of glucose CMRglc) and the TCA cycle flux ( VTCA) were measured in the same monkeys by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and 13C NMR spectroscopy, respectively. Registration of nuclear magnetic resonance (NMR) and PET data were used for comparison of CMRglc and VTCA in the exact same area of the brain. Both fluxes were in good agreement with literature values (CMR glc 0.23 ± 0.03 μmol/g min, VTCA = 0.53 ± 0.13 μmol/gmin). The resulting [ CMRglc/VTCA] ratio was 0.46 ± 0.12 ( n = 5, mean ± s.d.), not significantly different from the 0.5 expected when glucose is the sole fuel that is completely oxidized. Our results provide a cross-validation of both techniques. Comparison of CMRglc with VTCA is in agreement with a metabolic coupling between the TCA cycle and glycolysis under normal physiologic conditions.

scholarly journals Glutamatergic and GABAergic TCA Cycle and Neurotransmitter Cycling Fluxes in Different Regions of Mouse Brain

2013 ◽  
Vol 33 (10) ◽  
pp. 1523-1531 ◽  
Author(s):  
Vivek Tiwari ◽  
Susmitha Ambadipudi ◽  
Anant B Patel
Keyword(s):  
Cerebral Cortex ◽  
Mouse Brain ◽  
Ex Vivo ◽  
Tca Cycle ◽  
Metabolic Model ◽  
Nmr Studies ◽  
Inhibitory Function ◽  
The Tca Cycle ◽  
The Brain ◽  
C Nmr

The 13C nuclear magnetic resonance (NMR) studies together with the infusion of 13C-labeled substrates in rats and humans have provided important insight into brain energy metabolism. In the present study, we have extended a three-compartment metabolic model in mouse to investigate glutamatergic and GABAergic tricarboxylic acid (TCA) cycle and neurotransmitter cycle fluxes across different regions of the brain. The 13C turnover of amino acids from [1,6-13C2]glucose was monitored ex vivo using qH-[13C]-NMR spectroscopy. The astroglial glutamate pool size, one of the important parameters of the model, was estimated by a short infusion of [2-13C]acetate. The ratio Vcyc/VTCA was calculated from the steady-state acetate experiment. The 13C turnover curves of [4-13C]/[3-13C]glutamate, [4-13C]glutamine, [2-13C]/[3-13C]GABA, and [3-13C]aspartate from [1,6-13C2]glucose were analyzed using a three-compartment metabolic model to estimate the rates of the TCA cycle and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The glutamatergic TCA cycle rate was found to be highest in the cerebral cortex (0.91±0.05 μmol/g per minute) and least in the hippocampal region (0.64±0.07 μmol/g per minute) of the mouse brain. In contrast, the GABAergic TCA cycle flux was found to be highest in the thalamus-hypothalamus (0.28±0.01 μmol/g per minute) and least in the cerebral cortex (0.24±0.02 μmol/g per minute). These findings indicate that the energetics of excitatory and inhibitory function is distinct across the mouse brain.

scholarly journals β-Hydroxybutyrate Oxidation Promotes the Accumulation of Immunometabolites in Activated Microglia Cells

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 346
Author(s):  
Adrian Benito ◽  
Nabil Hajji ◽  
Kevin O’Neill ◽  
Hector C. Keun ◽  
Nelofer Syed
Keyword(s):  
Metabolic Regulation ◽  
Marker Gene ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Glycolytic Flux ◽  
Dihydroxyacetone Phosphate ◽  
Glycolytic Intermediate ◽  
Critical Set ◽  
The Tca Cycle ◽  
Bv2 Cells

Metabolic regulation of immune cells has arisen as a critical set of processes required for appropriate response to immunological signals. While our knowledge in this area has rapidly expanded in leukocytes, much less is known about the metabolic regulation of brain-resident microglia. In particular, the role of alternative nutrients to glucose remains poorly understood. Here, we use stable-isotope (13C) tracing strategies and metabolomics to characterize the oxidative metabolism of β-hydroxybutyrate (BHB) in human (HMC3) and murine (BV2) microglia cells and the interplay with glucose in resting and LPS-activated BV2 cells. We found that BHB is imported and oxidised in the TCA cycle in both cell lines with a subsequent increase in the cytosolic NADH:NAD+ ratio. In BV2 cells, stimulation with LPS upregulated the glycolytic flux, increased the cytosolic NADH:NAD+ ratio and promoted the accumulation of the glycolytic intermediate dihydroxyacetone phosphate (DHAP). The addition of BHB enhanced LPS-induced accumulation of DHAP and promoted glucose-derived lactate export. BHB also synergistically increased LPS-induced accumulation of succinate and other key immunometabolites, such as α-ketoglutarate and fumarate generated by the TCA cycle. Finally, BHB upregulated the expression of a key pro-inflammatory (M1 polarisation) marker gene, NOS2, in BV2 cells activated with LPS. In conclusion, we identify BHB as a potentially immunomodulatory metabolic substrate for microglia that promotes metabolic reprogramming during pro-inflammatory response.

Cerebral glucose metabolism during 30 minutes of moderate hypoxia and reoxygenation

1983 ◽  
Vol 245 (4) ◽  
pp. E365-E372
Author(s):  
D. Kintner ◽  
J. H. Fitzpatrick ◽  
J. A. Louie ◽  
D. D. Gilboe
Keyword(s):  
Glycolytic Flux ◽  
Oxygen Utilization ◽  
Lactate Oxidation ◽  
Cerebral Metabolic Rate ◽  
Show Evidence ◽  
Significant Release ◽  
Lactate Formation ◽  
Metabolite Synthesis ◽  
Posthypoxic Period ◽  
The Brain

In 50 separate experiments, isolated canine brain preparations were subjected to 15 or 30 min of either PaO2 30 mmHg or PaO2 40 mmHg perfusion followed by up to 60 min of reoxygenation at a normal PaO2. The cerebral metabolic rate for glucose (CMRGlu) increased 70-80% after 2 min of hypoxia but then returned to nearly the normal rate by the end of the 30-min period of hypoxia. Glycolytic flux appeared to be facilitated in both groups initially but was inhibited as the hypoxic period continued. This slowing of glycolysis after 15 or 30 min of hypoxia appears to be modulated by the regulatory enzyme phosphofructokinase. Glucose equivalents metabolized, based on CMRGlu plus brain glucose and glycogen disappearance, far exceed the glucose equivalents that can be accounted for on the basis of oxygen utilization and brain lactate formation. Thus, during hypoxia, some of the glucose equivalents must be utilized for synthesis of other metabolites. The glycolytic intermediates returned to normal after reoxygenation in the PaO2 40 mmHg preparations, but the PaO2 30 mmHg preparations continued to show evidence of decreased glycolysis and a lingering lactacidosis. Although posthypoxic oxygen uptake was sufficient to oxidize all glucose entering the brain, there was no significant release of accumulated lactate into the blood. Thus, the decrease in brain tissue lactate must have been the result of lactate oxidation. A significant amount of the glucose entering the brain during the posthypoxic period appears to be used for metabolite synthesis rather than energy production.

scholarly journals Method for Rapid MRI Quantification of Global Cerebral Metabolic Rate of Oxygen

2015 ◽  
Vol 35 (10) ◽  
pp. 1616-1622 ◽  
Author(s):  
Suliman Barhoum ◽  
Michael C Langham ◽  
Jeremy F Magland ◽  
Zachary B Rodgers ◽  
Cheng Li ◽  
...  
Keyword(s):  
Metabolic Rate ◽  
T Test ◽  
Quantitative Magnetic Resonance Imaging ◽  
Cerebral Metabolic Rate ◽  
Sagittal Sinus ◽  
Scan Time ◽  
Rapid Mri ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Good Agreement

A recently reported quantitative magnetic resonance imaging (MRI) method denoted OxFlow has been shown to be able to quantify whole-brain cerebral metabolic rate of oxygen (CMRO2) by simultaneously measuring oxygen saturation ( S v O 2) in the superior sagittal sinus and cerebral blood flow (CBF) in the arteries feeding the brain in 30 seconds, which is adequate for measurement at baseline but not necessarily in response to neuronal activation. Here, we present an accelerated version of the method (referred to as F-OxFlow) that quantifies CMRO2 in 8 seconds scan time under full retention of the parent method's capabilities and compared it with its predecessor at baseline in 10 healthy subjects. Results indicate excellent agreement between both sequences, with mean bias of 2.2% ( P = 0.18, two-tailed t-test), 3.4% ( P = 0.08, two-tailed t-test), and 2.0% ( P = 0.56, two-tailed t-test) for SvO2, CBF, and CMRO2, respectively. F-OxFlow's potential to monitor dynamic changes in SvO2, CBF, and CMRO2 is illustrated in a paradigm of volitional apnea applied to five of the study subjects. The sequence captured an average increase in SvO2, CBF, and CMRO2 of 10.1 ± 2.5%, 43.2 ± 9.2%, and 7.1 ± 2.2%, respectively, in good agreement with literature values. The method may therefore be suited for monitoring alterations in CBF and SvO2 in response to neurovascular stimuli.

scholarly journals Cerebral Metabolic Relationships for Selected Brain Regions in Healthy Adults

1984 ◽  
Vol 4 (1) ◽  
pp. 1-7 ◽  
Author(s):  
E. Jeffrey Metter ◽  
Walter H. Riege ◽  
David E. Kuhl ◽  
Michael E. Phelps
Keyword(s):  
Visual Processing ◽  
Occipital Cortex ◽  
Brain Regions ◽  
Emission Tomography ◽  
Inferior Parietal Lobule ◽  
Cerebral Metabolic Rate ◽  
Positron Emission ◽  
Metabolic Systems ◽  
The Matrix ◽  
The Brain

The local cerebral metabolic rate for glucose was determined in 26 regions of the brain in 31 healthy subjects who underwent resting fluorodeoxyglucose positron emission tomography. Intercorrelations among the 26 regional measures were accepted as reliable at p < 0.01 (r > 0.45), uncorrected for the number of measures. From the matrix two apparently separate functional metabolic systems were identified: (1) a superior system involving the superior and middle frontal gyri, the inferior parietal lobule, and the occipital cortex; and (2) an inferior system involving the inferior frontal, Broca's, and posterior temporal regions. Evidence is presented to suggest that the superior system is involved in visual processing, memory recognition, and decision making, while the inferior system seems to at least participate in language-related functions.

scholarly journals Quantitative Importance of the Pentose Phosphate Pathway Determined by Incorporation of 13C from [2-13C]- and [3-13C]Glucose into TCA Cycle Intermediates and Neurotransmitter Amino Acids in Functionally Intact Neurons

2012 ◽  
Vol 32 (9) ◽  
pp. 1788-1799 ◽  
Author(s):  
Eva M F Brekke ◽  
Anne B Walls ◽  
Arne Schousboe ◽  
Helle S Waagepetersen ◽  
Ursula Sonnewald
Keyword(s):  
Amino Acids ◽  
Pentose Phosphate Pathway ◽  
Cortical Neurons ◽  
Tca Cycle ◽  
Pentose Phosphate ◽  
Cerebellar Neurons ◽  
The Tca Cycle ◽  
Intact Brain ◽  
Tca Cycle Intermediates ◽  
The Brain

The brain is highly susceptible to oxidative injury, and the pentose phosphate pathway (PPP) has been shown to be affected by pathological conditions, such as Alzheimer's disease and traumatic brain injury. While this pathway has been investigated in the intact brain and in astrocytes, little is known about the PPP in neurons. The activity of the PPP was quantified in cultured cerebral cortical and cerebellar neurons after incubation in the presence of [2-13C]glucose or [3-13C]glucose. The activity of the PPP was several fold lower than glycolysis in both types of neurons. While metabolism of 13C-labeled glucose via the PPP does not appear to contribute to the production of releasable lactate, it contributes to labeling of tricarboxylic acid (TCA) cycle intermediates and related amino acids. Based on glutamate isotopomers, it was calculated that PPP activity accounts for ∼6% of glucose metabolism in cortical neurons and ∼4% in cerebellar neurons. This is the first demonstration that pyruvate generated from glucose via the PPP contributes to the synthesis of acetyl CoA for oxidation in the TCA cycle. Moreover, the fact that 13C labeling from glucose is incorporated into glutamate proves that both the oxidative and the nonoxidative stages of the PPP are active in neurons.

scholarly journals APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice

2018 ◽  
Author(s):  
Tal Nuriel ◽  
Delfina Larrea ◽  
David N. Guilfoyle ◽  
Leila Pirhaji ◽  
Kathleen Shannon ◽  
...  
Keyword(s):  
Acid Metabolism ◽  
Late Onset ◽  
Tca Cycle ◽  
Brain Regions ◽  
The Tca Cycle ◽  
Regional Vulnerability ◽  
Ε4 Allele ◽  
The Brain ◽  
Omic Data

ABSTRACTThe ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer’s disease (AD). However, the reason for the association between APOE4 and AD remains unclear. While much of the research has focused on the ability of the apoE4 protein to increase the aggregation and decrease the clearance of Aβ, there is also an abundance of data showing that APOE4 negatively impacts many additional processes in the brain, including bioenergetics. In order to gain a more comprehensive understanding of the APOE4’s role in AD pathogenesis, we performed a multi-omic analysis of APOE4 vs. APOE3 expression in the entorhinal cortex (EC) and primary visual cortex (PVC) of aged APOE mice. These studies revealed region-specific alterations in several bioenergetic pathways, including oxidative phosphorylation (OxPhos), the TCA-cycle and fatty acid metabolism. Follow-up analysis utilizing the Seahorse platform revealed decreased mitochondrial respiration in the hippocampus and cortex of aged APOE4 vs. APOE3 mice, but not in the EC of these mice. Additional studies, as well as the original multi-omic data suggest that bioernergetic pathways in the EC of aged APOE mice may be differentially regulated by APOE4 expression. Given the importance of the EC as one of the first regions to be affected by AD pathology in humans, this differential bionenergetic regulation observed in the EC vs. other brain regions of aged APOE4 mice may play an important role in the pathogenesis of AD, particularly among APOE4 carriers.

Biosynthesis of Pyoluteorin: A Mixed Polyketide-Tricarboxylic Acid Cycle Origin Demonstrated by [1,2-13C2]Acetate Incorporation

1986 ◽  
Vol 41 (5-6) ◽  
pp. 532-536 ◽  
Author(s):  
D. A. Cuppels ◽  
C. R. Howell ◽  
R. D. Stipanovic ◽  
A. Stoessl ◽  
J. B. Stothers
Keyword(s):  
Nmr Spectroscopy ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Acetate Incorporation ◽  
Acid Cycle ◽  
The Tca Cycle ◽  
Starter Unit ◽  
C Nmr

The incorporation of [1,2-13C2]acetate into the bacterial phytotoxin pyoluteorin (1) as determined by 13C NMR spectroscopy occurs in a pattern consistent with the biosynthesis of the molecule as a tetraketide in which proline, or an equivalent precursor derived from the TCA cycle, serves as the starter unit.

scholarly journals Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor

2009 ◽  
Vol 296 (2) ◽  
pp. R383-R393 ◽  
Author(s):  
Matthew T. Andrews ◽  
Kevin P. Russeth ◽  
Lester R. Drewes ◽  
Pierre-Gilles Henry
Keyword(s):  
Tca Cycle ◽  
Serum Levels ◽  
Reciprocal Relationship ◽  
Body Temperatures ◽  
Spermophilus Tridecemlineatus ◽  
The Tca Cycle ◽  
Adaptive Mechanisms ◽  
Wide Range ◽  
Low Levels ◽  
The Brain

Hibernating mammals use reduced metabolism, hypothermia, and stored fat to survive up to 5 or 6 mo without feeding. We found serum levels of the fat-derived ketone, d-β-hydroxybutyrate (BHB), are highest during deep torpor and exist in a reciprocal relationship with glucose throughout the hibernation season in the thirteen-lined ground squirrel ( Spermophilus tridecemlineatus). Ketone transporter monocarboxylic acid transporter 1 (MCT1) is upregulated at the blood-brain barrier, as animals enter hibernation. Uptake and metabolism of 13C-labeled BHB and glucose were measured by high-resolution NMR in both brain and heart at several different body temperatures ranging from 7 to 38°C. We show that BHB and glucose enter the heart and brain under conditions of depressed body temperature and heart rate but that their utilization as a fuel is highly selective. During arousal from torpor, glucose enters the brain over a wide range of body temperatures, but metabolism is minimal, as only low levels of labeled metabolites are detected. This is in contrast to BHB, which not only enters the brain but is also metabolized via the tricarboxylic acid (TCA) cycle. A similar situation is seen in the heart as both glucose and BHB are transported into the organ, but only 13C from BHB enters the TCA cycle. This finding suggests that fuel selection is controlled at the level of individual metabolic pathways and that seasonally induced adaptive mechanisms give rise to the strategic utilization of BHB during hibernation.

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