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.

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 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.

TCA cycle activity in Saccharomyces cerevisiae is a function of the environmentally determined specific growth and glucose uptake rates

Microbiology ◽  
2004 ◽  
Vol 150 (4) ◽  
pp. 1085-1093 ◽  
Author(s):  
Lars M. Blank ◽  
Uwe Sauer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Growth Rate ◽  
Glucose Uptake ◽  
Environmental Conditions ◽  
Specific Growth ◽  
Tca Cycle ◽  
Glucose Sensing ◽  
The Tca Cycle ◽  
Uptake Rates ◽  
Wide Range

Metabolic responses of Saccharomyces cerevisiae to different physical and chemical environmental conditions were investigated in glucose batch culture by GC-MS-detected mass isotopomer distributions in proteinogenic amino acids from 13C-labelling experiments. For this purpose, GC-MS-based metabolic flux ratio analysis was extended from bacteria to the compartmentalized metabolism of S. cerevisiae. Generally, S. cerevisiae was shown to have low catabolic fluxes through the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle. Notably, respiratory TCA cycle fluxes exhibited a strong correlation with the maximum specific growth rate that was attained under different environmental conditions, including a wide range of pH, osmolarity, decoupler and salt concentrations, but not temperature. At pH values of 4·0 to 6·0 with near-maximum growth rates, the TCA cycle operated as a bifurcated pathway to fulfil exclusively biosynthetic functions. Increasing or decreasing the pH beyond this physiologically optimal range, however, reduced growth and glucose uptake rates but increased the ‘cyclic’ respiratory mode of TCA cycle operation for catabolism. Thus, the results indicate that glucose repression of the TCA cycle is regulated by the rates of growth or glucose uptake, or signals derived from these. While sensing of extracellular glucose concentrations has a general influence on the in vivo TCA cycle activity, the growth-rate-dependent increase in respiratory TCA cycle activity was independent of glucose sensing.

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.

ADRENOCORTICAL FUNCTION IN PATIENTS WITH ACUTE SEVERE BRAIN AND PITUITARY LESION

1962 ◽  
Vol 40 (2) ◽  
pp. 254-262 ◽  
Author(s):  
H. H. Bassøe ◽  
R. Emberland ◽  
E. Glück ◽  
K. F. Støa
Keyword(s):  
Pituitary Gland ◽  
Adrenal Cortex ◽  
Artificial Ventilation ◽  
Practical Significance ◽  
Adrenocortical Function ◽  
The Third ◽  
Low Levels ◽  
Pituitary Lesion ◽  
Steroid Excretion ◽  
The Brain

ABSTRACT The steroid excretion and the plasma corticosteroids were investigated in three patients with necrosis of the brain and of the pituitary gland. The patients were kept alive by artificial ventilation. In two of the patients the neutral 17-ketosteroids and the 17-hydrocorticosteroids fell to extremely low levels. At the same time, the number of eosinophil cells showed a tendency to increase. Corticotrophin administered intravenously twice to the third patient had a stimulating effect on the adrenal cortex. The theoretical and practical significance of these findings is discussed.

Recovery of thyroid function with a decreased titre of antimicrosomal antibody in a hypothyroid man with Hashimoto's thyroiditis

1983 ◽  
Vol 102 (4) ◽  
pp. 531-534 ◽  
Author(s):  
Makiko Yamamoto ◽  
Kazuro Kaise ◽  
Hirofumi Kitaoka ◽  
Katsumi Yoshida ◽  
Nobuko Kaise ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Serum Levels ◽  
Hashimoto's Thyroiditis ◽  
Thyroid Peroxidase ◽  
Normal Range ◽  
Surgical Biopsy ◽  
Low Levels ◽  
Serum Thyroid Hormones ◽  
Antimicrosomal Antibody ◽  
Serum Tsh

Abstract. A 36 year old man with a diffuse goitre, signs of mild hypothyroidism, strikingly low levels of T4 (0.9 μg/dl) and T3 (24 ng/dl), elevated TSH (140 μU/ml) and elevated microsomal haemagglutination antibody (MCHA, 1:409 600), subsequently became non-goitrous and euthyroid with a decreased titre of antimicrosomal antibody without any medication. At the time of surgical biopsy, serum levels of T4 and T3 had risen to the normal range (4.6 μg/dl and 73 ng/dl, respectively), serum TSH had decreased to 30 μU/ml and the titre of MCHA to 1:25 600. Thyroid specimens showed Hashimoto's thyroiditis. The activity of thyroid peroxidase (TPO) was normal. The latest examination, 1 year and 3 months after initial evaluation, showed that the patient remained euthyroid with no goitre, that serum thyroid hormones were within the normal range (T4 7.7 μg/dl and T3 97 ng/dl), and that TSH was not detectable. The titre of MCHA decreased strikingly to 1:400.

ADRENERGIC INPUTS TO THE AMYGDALA AND THE CONTROL OF GONADOTROPHIN RELEASE

1979 ◽  
Vol 90 (3) ◽  
pp. 385-393 ◽  
Author(s):  
José Borrell ◽  
Flavio Piva ◽  
Luciano Martini
Keyword(s):  
Brain Stem ◽  
Dopamine Receptor ◽  
Serum Levels ◽  
Female Rats ◽  
Receptor Blocker ◽  
Dopaminergic Drug ◽  
Gonadotrophin Secretion ◽  
Biphasic Effect ◽  
Adrenergic Blocker ◽  
The Brain

ABSTRACT Drugs able to mimic or to antagonize the action of catecholamines have been implanted bilaterally into the basomedial region of the amygdala of adult castrated female rats. The animals were killed at different intervals after the implantation of the different drugs, and serum levels of LH and FSH were measured by radioimmunoassay. The results have shown that the intra-amygdalar implantation of the alpha-adrenergic blocker phenoxybenzamine induces a significant increase of the release both of LH and FSH. The implantation of the beta-adrenergic blocker propranolol brings about a rise of LH only. The dopamine receptor blocker pimozide stimulates the release of LH and exerts a biphasic effect (stimulation followed by inhibition) of FSH secretion. The alpha-receptor stimulant clonidine and the dopaminergic drug 2-Br-alpha-ergocryptine were without significant effects. From these observations it is suggested that the adrenergic signals reaching the basomedial area of the amygdala (possibly from the brain stem) may be involved in the modulation of gonadotrophin secretion.

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>

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