scholarly journals Glutamate dehydrogenase is essential to sustain neuronal oxidative energy metabolism during stimulation

2017 ◽  
Vol 38 (10) ◽  
pp. 1754-1768 ◽  
Author(s):  
Michaela C Hohnholt ◽  
Vibe H Andersen ◽  
Jens V Andersen ◽  
Sofie K Christensen ◽  
Melis Karaca ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Glutamate Dehydrogenase ◽  
Energy Demand ◽  
Glucose Deprivation ◽  
Brain Mitochondria ◽  
Glutamine Metabolism ◽  
Oxidative Deamination ◽  
Oxidative Energy Metabolism ◽  
The Brain

The enzyme glutamate dehydrogenase (GDH; Glud1) catalyzes the (reversible) oxidative deamination of glutamate to α-ketoglutarate accompanied by a reduction of NAD+ to NADH. GDH connects amino acid, carbohydrate, neurotransmitter and oxidative energy metabolism. Glutamine is a neurotransmitter precursor used by neurons to sustain the pool of glutamate, but glutamine is also vividly oxidized for support of energy metabolism. This study investigates the role of GDH in neuronal metabolism by employing the Cns- Glud1−/− mouse, lacking GDH in the brain (GDH KO) and metabolic mapping using 13C-labelled glutamine and glucose. We observed a severely reduced oxidative glutamine metabolism during glucose deprivation in synaptosomes and cultured neurons not expressing GDH. In contrast, in the presence of glucose, glutamine metabolism was not affected by the lack of GDH expression. Respiration fuelled by glutamate was significantly lower in brain mitochondria from GDH KO mice and synaptosomes were not able to increase their respiration upon an elevated energy demand. The role of GDH for metabolism of glutamine and the respiratory capacity underscore the importance of GDH for neurons particularly during an elevated energy demand, and it may reflect the large allosteric activation of GDH by ADP.

Energy Metabolism Impairment in Migraine

2019 ◽  
Vol 26 (34) ◽  
pp. 6253-6260 ◽  
Author(s):  
Sabina Cevoli ◽  
Valentina Favoni ◽  
Pietro Cortelli
Keyword(s):  
Energy Metabolism ◽  
Energy Demand ◽  
Energy Production ◽  
Mitochondrial Respiratory Chain ◽  
Migraine Prophylaxis ◽  
Resonance Spectroscopy ◽  
Oxidative Energy Metabolism ◽  
Spectroscopy Studies ◽  
The Brain ◽  
Brain Energy

Migraine is a common disabling neurological disorder which is characterised by a recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an updated overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold creates metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine.

Energy Metabolism and Effects of Energy Depletion or Exposure to Glutamate

1992 ◽  
Vol 70 (S1) ◽  
pp. S107-S112 ◽  
Author(s):  
Louis Sokoloff
Keyword(s):  
Energy Metabolism ◽  
Brain Cells ◽  
Cerebral Hypoxia ◽  
Energy Depletion ◽  
Pathological Conditions ◽  
Oxidative Energy Metabolism ◽  
The Subject ◽  
Tissue Acidosis ◽  
The Brain

The entire program of the first day of the IBRO satellite meeting entitled Ions, Water, and Energy in Brain Cells was devoted to the subject of energy. There were three sessions on the topics of energy metabolism, activation, and development and pathological conditions, followed by a final general discussion on the contents of the day's topics. During this general discussion there were spirited exchanges on the role of glycogen in the energy metabolism of the brain, on the metabolic source of the energy consumed by functional activity, e.g., glycolytic or oxidative energy metabolism, and on the sources of the acid-equivalents that are responsible for the tissue acidosis accompanying cerebral hypoxia. Despite the arguments pro and con presented on all of the issues that were discussed, it is doubtful that a consensus was achieved on most of the issues.Key words: glycogen, glycolysis, oxidative metabolism, acidosis, energy metabolism.

scholarly journals Aspartoacylase Supports Oxidative Energy Metabolism during Myelination

2012 ◽  
Vol 32 (9) ◽  
pp. 1725-1736 ◽  
Author(s):  
Jeremy S Francis ◽  
Louise Strande ◽  
Vladamir Markov ◽  
Paola Leone
Keyword(s):  
Energy Metabolism ◽  
Postnatal Development ◽  
Strong Association ◽  
Canavan Disease ◽  
Lipid Synthesis ◽  
Systematic Analysis ◽  
Early Postnatal Development ◽  
Neuronal Viability ◽  
Oxidative Energy Metabolism ◽  
The Brain

The inherited leukodystrophy Canavan disease arises due to a loss of the ability to catabolize N-acetylaspartic acid (NAA) in the brain and constitutes a major point of focus for efforts to define NAA function. Accumulation of noncatabolized NAA is diagnostic for Canavan disease, but contrasts with the abnormally low NAA associated with compromised neuronal integrity in a broad spectrum of other clinical conditions. Experimental evidence for NAA function supports a role in white matter lipid synthesis, but does not explain how both elevated and lowered NAA can be associated with pathology in the brain. We have undertaken a systematic analysis of postnatal development in a mouse model of Canavan disease that delineates development and pathology by identifying markers of oxidative stress preceding oligodendrocyte loss and dysmyelination. These data suggest a role for NAA in the maintenance of metabolic integrity in oligodendrocytes that may be of relevance to the strong association between NAA and neuronal viability. N-acetylaspartic acid is proposed here to support lipid synthesis and energy metabolism via the provision of substrate for both cellular processes during early postnatal development.

scholarly journals Dissociated Expression of Mitochondrial and Cytosolic Creatine Kinases in the Human Brain: A New Perspective on the Role of Creatine in Brain Energy Metabolism

2013 ◽  
Vol 33 (8) ◽  
pp. 1295-1306 ◽  
Author(s):  
Matthew TJ Lowe ◽  
Eric H Kim ◽  
Richard LM Faull ◽  
David L Christie ◽  
Henry J Waldvogel
Keyword(s):  
Energy Metabolism ◽  
Human Brain ◽  
High Energy ◽  
Cellular Energy ◽  
Neuronal Populations ◽  
Neurologic Function ◽  
New Perspective ◽  
The Brain ◽  
Brain Energy

The phosphocreatine/creatine kinase (PCr/CK) system in the brain is defined by the expression of two CK isozymes: the cytosolic brain-type CK (BCK) and the ubiquitous mitochondrial CK (uMtCK). The system plays an important role in supporting cellular energy metabolism by buffering adenosine triphosphate (ATP) consumption and improving the flux of high-energy phosphoryls around the cell. This system is well defined in muscle tissue, but there have been few detailed studies of this system in the brain, especially in humans. Creatine is known to be important for neurologic function, and its loss from the brain during development can lead to mental retardation. This study provides the first detailed immunohistochemical study of the expression pattern of BCK and uMtCK in the human brain. A strikingly dissociated pattern of expression was found: uMtCK was found to be ubiquitously and exclusively expressed in neuronal populations, whereas BCK was dominantly expressed in astrocytes, with a low and selective expression in neurons. This pattern indicates that the two CK isozymes are not widely coexpressed in the human brain, but rather are selectively expressed depending on the cell type. These results suggest that the brain cells may use only certain properties of the PCr/CK system depending on their energetic requirements.

Newer aspects of glutamine/glutamate metabolism: the role of acute pH changes

1999 ◽  
Vol 277 (4) ◽  
pp. F493-F497 ◽  
Author(s):  
Itzhak Nissim
Keyword(s):  
Glutamate Metabolism ◽  
Oxidative Deamination ◽  
Carbamyl Phosphate ◽  
Ph Changes ◽  
Extracellular Compartment ◽  
Neuronal Metabolism ◽  
Glutamine Synthesis ◽  
Kidney Liver ◽  
The Brain

This review focuses on the role of acute pH changes in the regulation of Gln/Glu metabolism in the kidney, liver, and brain. Alterations of proton concentration ([H+]) profoundly affect flux through phosphate-dependent glutaminase (PDG) or glutamate dehydrogenase (GDH), the primary enzymes responsible for mitochondrial metabolism of glutamine and glutamate, respectively. In the kidney, acute acidosis stimulates Gln uptake and its metabolism via the PDG pathway. The Glu formed from Gln can be removed via 1) oxidative deamination through the GDH reaction, 2) transamination reactions, and 3) transport of Glu from intracellular to extracellular compartment, thereby diminishing the intramitochondrial pool of glutamate sufficiently to stimulate flux through the PDG pathway. Converse changes may occur with increased pH. In the liver, acidosis diminishes the rate of Gln and Glu metabolism via the PDG and GDH pathways, but stimulates glutamine synthesis (i.e., glutamine recycling). Alkalosis has little effect. Hepatic Gln metabolism via the PDG pathway has a central role in ureagenesis via 1) supplementation of nitrogen for the synthesis of carbamyl phosphate, and 2) providing glutamate for N-acetylglutamate synthesis. In the brain, Gln/Glu metabolism links ammonia detoxification and energy metabolism via 1) detoxification of ammonia and excess glutamate by glutamine synthesis in astrocytes, 2) formation and export of glutamine to neurons where it is metabolized to glutamate and GABA, and 3) production of α-ketoglutarate and lactate from Glu and their transport to neurons. Changes in intracellular pH associated with changes in cellular [K+] may have a key role in the regulation of these processes of glial-neuronal metabolism of Gln/Glu metabolism.

Evidence that levels of malate dehydrogenase and fumarase are increased by cAMP in rat myotubes

1984 ◽  
Vol 247 (1) ◽  
pp. C33-C38 ◽  
Author(s):  
J. C. Lawrence ◽  
W. J. Salsgiver
Keyword(s):  
Energy Metabolism ◽  
Malate Dehydrogenase ◽  
Potential Role ◽  
Primary Cultures ◽  
Phosphodiesterase Inhibitors ◽  
Dibutyryl Camp ◽  
Rat Skeletal Muscle ◽  
Oxidative Energy Metabolism ◽  
Enzymes Of Energy Metabolism

We have investigated the potential role of adenosine 3',5'-cyclic monophosphate (cAMP) in controlling levels of enzymes of energy metabolism in primary cultures of rat skeletal muscle cells. Incubating myotubes with cholera toxin or forskolin (2 persistent activators of adenylate cyclase) significantly increased the levels of two enzymes of oxidative metabolism, fumarase and malate dehydrogenase. These enzymes were also increased (1.5- to 2.0-fold) by phosphodiesterase inhibitors (caffeine, theophylline, theobromine, 3-isobutyl-1-methylxanthine, papaverine, MJ 1988, Ro 20–1724, or SQ 20009) and the cAMP derivatives: 8-bromo-cAMP or dibutyryl cAMP. In contrast two enzymes of glycolytic metabolism, lactate dehydrogenase and pyruvate kinase, were not consistently affected by these agents. The results presented provide strong evidence that an increase in cAMP can lead to an increase in certain enzymes of oxidative energy metabolism.

scholarly journals The pathway of glutamate metabolism in rat brain mitochondria

1977 ◽  
Vol 168 (3) ◽  
pp. 521-527 ◽  
Author(s):  
Steven C. Dennis ◽  
John B. Clark
Keyword(s):  
Rat Brain ◽  
Glutamate Dehydrogenase ◽  
Brain Mitochondria ◽  
Ammonia Production ◽  
Glutamate Metabolism ◽  
Oxidative Deamination ◽  
Rat Brain Mitochondria ◽  
Major Route

1. The pathway of glutamate metabolism in non-synaptic rat brain mitochondria was investigated by measuring glutamate, aspartate and ammonia concentrations and oxygen uptakes in mitochondria metabolizing glutamate or glutamine under various conditions. 2. Brain mitochondria metabolizing 10mm-glutamate in the absence of malate produce aspartate at 15nmol/min per mg of protein, but no detectable ammonia. If amino-oxyacetate is added, the aspartate production is decreased by 80% and ammonia production is now observed at a rate of 6.3nmol/min per mg of protein. 3. Brain mitochondria metabolizing glutamate at various concentrations (0–10mm) in the presence of 2.5mm-malate produce aspartate at rates that are almost stoicheiometric with glutamate disappearance, with no detectable ammonia production. In the presence of amino-oxyacetate, although the rate of aspartate production is decreased by 75%, ammonia production is only just detectable (0.3nmol/min per mg of protein). 4. Brain mitochondria metabolizing 10mm-glutamine and 2.5mm-malate in States 3 and 4 were studied by using glutamine as a source of intramitochondrial glutamate without the involvement of mitochondrial translocases. The ammonia production due to the oxidative deamination of glutamate produced from the glutamine was estimated as 1nmol/min per mg of protein in State 3 and 3nmol/min per mg of protein in State 4. 5. Brain mitochondria metabolizing 10mm-glutamine in the presence of 1mm-amino-oxyacetate under State-3 conditions in the presence or absence of 2.5mm-malate showed no detectable aspartate production. In both cases, however, over the first 5min, ammonia production from the oxidative deamination of glutamate was 21–27nmol/min per mg of protein, but then decreased to approx. 1–1.5nmol/min per mg. 6. It is concluded that the oxidative deamination of glutamate by glutamate dehydrogenase is not a major route of metabolism of glutamate from either exogenous or endogenous (glutamine) sources in rat brain mitochondria.

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