Glutamine and glucose metabolism in thymocytes from normal and spontaneously diabetic BB rats

1991 ◽  
Vol 69 (12) ◽  
pp. 801-808 ◽  
Author(s):  
Guoyao Wu ◽  
Catherine J. Field ◽  
Errol B. Marliss
Keyword(s):  
Energy Metabolism ◽  
Krebs Cycle ◽  
Major Product ◽  
Lymphoid Organs ◽  
Glutamine Metabolism ◽  
Potential Production ◽  
Atp Production ◽  
Bb Rats ◽  
Oxidation Of Glucose ◽  
Diabetic Syndrome

Metabolism of glutamine and glucose was studied in thymocytes from normal rats and BB rats with the spontaneous autoimmune diabetic syndrome to assess their potential roles as fuels. The major measured products from glucose were lactate and, to a lesser extent, CO2, and pyruvate. Glutamine had no effect on the rates of their production from glucose. Glutamine was metabolized to ammonia, aspartate, glutamate, and CO2, with aspartate being the major product of carbons from glutamine in the absence of glucose. Glucose markedly decreased the formation of ammonia, aspartate, and CO2 from glutamine, but increased that of glutamate, with an overall decrease in glutamine utilization by 55%. More glutamate than aspartate was produced from glutamine in the presence of glucose. The potential production of ATP from glucose was similar to that when glutamine was present alone. However, glucose markedly decreased production of ATP from glutamine, but not vice versa. This resulted in ATP production from glucose being 2.5 times that from glutamine when both substrates were present. The oxidation of glucose to CO2 via the Krebs cycle accounts for 75–80% of glucose-derived ATP production. Cellular ATP levels markedly decreased in the absence of exogenous substrates, but were constant throughout a 2-h incubation in the presence of glutamine, glucose, or both. There were no differences in thymocyte glucose or glutamine metabolism between normal and diabetic BB rats, in contrast to previous findings in peripheral lymphoid organs. Our results suggest that glucose is a more important fuel than glutamine for "resting" thymocytes, again in contrast to the cells of peripheral lymphoid organs in which glutamine is as important as glucose as a fuel. The enhanced energy metabolism found in the cells from peripheral lymphoid organs of diabetic BB rats, if due to T-lymphocytes, must occur after their migration out of the thymus.Key words: glutaminolysis, glycolysis, thymocytes, ATP, BB rats.

scholarly journals Elevated glutamine metabolism in splenocytes from spontaneously diabetic BB rats

1991 ◽  
Vol 274 (1) ◽  
pp. 49-54 ◽  
Author(s):  
G Wu ◽  
C J Field ◽  
E B Marliss
Keyword(s):  
Diabetic Rats ◽  
Glutamine Metabolism ◽  
Co2 Production ◽  
Diabetic Rat ◽  
Bb Rat ◽  
Isolated Cells ◽  
Atp Production ◽  
Glutamate Production ◽  
Insulin Dependent ◽  
Diabetic Syndrome

To investigate the metabolic fates of glutamine in splenocytes from the BB rat with spontaneous immunologically mediated insulin-dependent diabetes, freshly isolated cells were incubated in Krebs-Ringer Hepes buffer with 1.0 mM-[U-14C]glutamine and 0, 4 mM- or 15 mM-glucose. (1) The major products of glutamine metabolism in splenocytes from normal and diabetic rats were ammonia, glutamate, aspartate and CO2. (2) The addition of glucose increased (P less than 0.01) glutamate production, but decreased (P less than 0.01) aspartate and CO2 production from glutamine, as compared with the values obtained in the absence of glucose. However, there were no differences in these metabolites of glutamine at 4 mM- and 15 mM-glucose. (3) At all glucose concentrations used, the productions of ammonia, glutamate, aspartate and CO2 from glutamine were all markedly increased (P less than 0.01) in splenocytes from diabetic rats. (4) Potential ATP production from glutamine in the splenocytes was similar to that from glucose, and was increased in cells from the diabetic rat. (5) ATP concentrations were increased (P less than 0.01) in diabetic-rat splenocytes in the presence of glutamine with or without glucose. (6) Our results demonstrate that glutamine is an important energy substrate for splenocytes and suggest that the increased glutamine metabolism may be associated with the activation of certain subsets of splenocytes in the immunologically mediated diabetic syndrome.

scholarly journals Energy-modulating vitamins – a new combinatorial therapy prevents cancer cachexia in rat mammary carcinoma

2005 ◽  
Vol 93 (6) ◽  
pp. 901-909 ◽  
Author(s):  
Selvanathan Saravana Perumal ◽  
Palanivelu Shanthi ◽  
Panchanadham Sachdanandam
Keyword(s):  
Body Weight ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Oral Administration ◽  
Cancer Cells ◽  
Mammary Carcinoma ◽  
Cancer Cachexia ◽  
Krebs Cycle ◽  
Mitochondrial Enzymes ◽  
Atp Production

Mitochondria are the major intracellular organelles producing ATP molecules via the electron transport chain. Cancer cells have a deviant energy metabolism, and a high rate of glycolysis is related to a high degree of dedifferentiation and proliferation. The overall net ATP production is diminished with cancer, which ultimately leads to cancer cachexia. The present study was designed to investigate the altered energy metabolism in cancer cells and to enhance ATP production in the normal host cell metabolism by enhancing the activities of mitochondrial enzymes, using energy-modulating vitamins, and thus prevent cancer cachexia. Female Sprague–Dawley rats were selected for the experimental study. Mammary carcinoma was induced by the oral administration of 7,12-dimethylbenz[a]anthracene (25 mg/kg body weight), and treatment was started by the oral administration of the energy-modulating vitamins riboflavin (45 mg/kg body weight per d), niacin (100 mg/kg body weight per d) and coenzyme Q10(40 mg/kg body weight per d) for 28 d. Mitochondria were isolated from the mammary gland and liver of all four groups, and the Krebs cycle and oxidative phosphorylation enzymes were assayed. In mammary carcinoma-bearing animals, the activities of the Krebs cycle and oxidative phosphorylation enzymes were significantly decreased. These activities were restored to a greater extent in animals treated with energy-modulating vitamins. From these experimental results, one may hypothesize that the combination therapy of energy-modulating vitamins could be of major therapeutic value in breast cancer.

scholarly journals Disruption of Glycolysis, TCA Cycle, Respiratory Chain, Calcium and Iron Homeostasis in Doxorubicin Induced Cardiomyopathy-An In-silico Approach

2021 ◽  
Vol 12 (6) ◽  
pp. 8527-8542
Keyword(s):  
Energy Metabolism ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Krebs Cycle ◽  
Atp Depletion ◽  
Critical Function ◽  
Free Iron ◽  
Atp Production ◽  
Cardiac Energy Metabolism ◽  
Cardiac Energy

Doxorubicin is a well-known anthracycline antibiotic that is frequently used to treat a variety of malignancies. However, its clinical use is limited due to its adverse consequences, most notably cardiomyopathy. In the present work, we evaluated the molecular mechanisms behind the impairment of cardiac energetics in doxorubicin-induced cardiomyopathy. According to molecular docking, the interaction of doxorubicin with phosphofructokinase (PKF) and α-enolase is likely to negatively affect glycolysis. The interaction between doxorubicin with HMOX1 results in the accumulation of free iron. The free iron contributes to the heme-driven toxicity and the oxidizing environment that results in reactive oxygen species (ROS) production resulting from cell death. Additionally, the interaction of doxorubicin with HMOX1 impairs the availability of iron required for the Krebs cycle and ETC function. The interaction between doxorubicin and PINK1 results in a reduced membrane potential, which results in calcium accumulation. On the other hand, a lack of iron and calcium in the mitochondrial matrix results in ATP depletion, impairing the Krebs cycle activity. At the same time, the primary cause of doxorubicin-induced cardiomyopathy is cardiac energy metabolism. Thus, our work shows that doxorubicin impairs the activity of PFK, α-enolase, HMOX1, and PINK1, resulting in ATP production failure. As a result of changes in the heart energy metabolism, this ultimately leads to dilated cardiomyopathy caused by doxorubicin. Understanding the critical function of cardiac energy metabolism in doxorubicin-induced cardiomyopathy is critical for overcoming the obstacles that effectively limit the clinical effectiveness of this life-saving anti-cancer treatment.

scholarly journals Energy Metabolism Decline in the Aging Brain; Pathogenesis of Neurodegenerative Disorders

2020 ◽  
Author(s):  
Janusz Błaszczyk
Keyword(s):  
Energy Metabolism ◽  
Neurodegenerative Diseases ◽  
Krebs Cycle ◽  
Brain Structures ◽  
The Elderly ◽  
Review Article ◽  
Aging Brain ◽  
Salvage Pathway ◽  
Atp Production ◽  
The Brain

A growing body of evidence indicates that aging of the brain is strictly related to the decline of energy metabolism. In particular, in older adults, the neuronal metabolism of glucose declines steadily resulting in a growing deficit of ATP production. The decline is evoked by deficient NAD recovery in the salvage pathway and subsequent impairment of the Krebs cycle. NAD deficit impairs also the activity of NAD-dependent enzymes. All these open vicious circles of neurodegeneration and neuronal death. Some brain structures are particularly prone to aging and neurodegeneration. These are pathological foci of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This review article summarizes the impacts and mutual relationships between metabolic processes both on neuronal and brain levels. It also provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.

Evolutionary Consequences of Tradeoffs between Yield and Rate of ATP Production

2002 ◽  
Vol 216 (1) ◽  
Author(s):  
Thomas Pfeiffer ◽  
Sebastian Bonhoeffer
Keyword(s):  
Game Theory ◽  
Population Dynamics ◽  
Energy Metabolism ◽  
Adenosine Triphosphate ◽  
Organic Material ◽  
High Yield ◽  
Atp Production ◽  
Cellular Processes ◽  
Quantitative Properties ◽  
Evolutionary Consequences

Adenosine triphosphate (ATP) is a key compound in the energy metabolism of cells and is required to drive vital biochemical reactions. In heterotrophic organisms ATP production is coupled to the degradation of energy-rich organic material taken up from the environment. In the transfer of the environmental energy to cellular processes heterotrophs face a tradeoff, since the conversion of the environmental energy into ATP cannot be both maximally fast and efficient. Here we show how tradeoffs between rate and yield of ATP production arise firstly from thermodynamical principles, and secondly for the ATP production by respiration and fermentation. Using methods derived from game theory and population dynamics we investigate the evolutionary consequences for both tradeoffs. We show that spatially structured environments enable the evolution of efficient pathways with high yield. The strategies of ATP production realized in a population, however, depend on the quantitative properties of the tradeoffs.

scholarly journals Acetate represents a major product of heptanoate and octanoate β-oxidation in hepatocytes isolated from neonatal piglets

1996 ◽  
Vol 318 (1) ◽  
pp. 235-240 ◽  
Author(s):  
Xi LIN ◽  
Sean H. ADAMS ◽  
Jack ODLE
Keyword(s):  
Fatty Acid ◽  
Organic Acids ◽  
Chain Length ◽  
Ketone Bodies ◽  
Krebs Cycle ◽  
Major Product ◽  
Carbon Accounting ◽  
Minor Amount ◽  
Fatty Acid Carbon ◽  
Carboxyl Carbon

An experiment was conducted to explore the nature of the radiolabel distribution in acid-soluble products (ASPs) resulting from the oxidation of [1-14C]C7:0 or C8:0 by isolated piglet hepatocytes. The differences between odd and even chain-length and the impacts of valproate and malonate upon the rate of β-oxidation and ASP characteristics were tested. A minor amount of fatty acid carboxyl carbon (⩽ 10% of organic acids identified by radio-HPLC) accumulated in ketone bodies regardless of chain-length or inhibitor used. In all cases, acetate represented the major reservoir of carboxyl carbon, accounting for 60–70% of radiolabel in identified organic acids. Cells given [1-14C]C7:0 accumulated 85% more carboxyl carbon in Krebs cycle intermediates when compared with C8:0, while accumulation in acetate was unaffected. The results are consistent with the hypothesis that anaplerosis from odd-carbon fatty acids affects the oxidative fate of fatty acid carbon. The piglet appears unique in that non-ketogenic routes of fatty acid carbon flow (i.e. acetogenesis) predominate in the liver of this species.

scholarly journals The Krebs Cycle Enzyme α-Ketoglutarate Decarboxylase Is an Essential Glycosomal Protein in Bloodstream African Trypanosomes

2014 ◽  
Vol 14 (3) ◽  
pp. 206-215 ◽  
Author(s):  
Steven Sykes ◽  
Anthony Szempruch ◽  
Stephen Hajduk
Keyword(s):  
Plasma Membranes ◽  
Fluorescent Protein ◽  
Krebs Cycle ◽  
Content Type ◽  
African Trypanosomes ◽  
Atp Production ◽  
Cycle Enzyme ◽  
A Cell ◽  
Direct Localization ◽  
Green Fluorescent

ABSTRACT α-Ketoglutarate decarboxylase (α-KDE1) is a Krebs cycle enzyme found in the mitochondrion of the procyclic form (PF) of Trypanosoma brucei . The bloodstream form (BF) of T. brucei lacks a functional Krebs cycle and relies exclusively on glycolysis for ATP production. Despite the lack of a functional Krebs cycle, α-KDE1 was expressed in BF T. brucei and RNA interference knockdown of α-KDE1 mRNA resulted in rapid growth arrest and killing. Cell death was preceded by progressive swelling of the flagellar pocket as a consequence of recruitment of both flagellar and plasma membranes into the pocket. BF T. brucei expressing an epitope-tagged copy of α-KDE1 showed localization to glycosomes and not the mitochondrion. We used a cell line transfected with a reporter construct containing the N-terminal sequence of α-KDE1 fused to green fluorescent protein to examine the requirements for glycosome targeting. We found that the N-terminal 18 amino acids of α-KDE1 contain overlapping mitochondrion- and peroxisome-targeting sequences and are sufficient to direct localization to the glycosome in BF T. brucei . These results suggest that α-KDE1 has a novel moonlighting function outside the mitochondrion in BF T. brucei .

Enhancement of antitumor activity by epigenetic regulation of tumour-specific T cells

Impact ◽  
2021 ◽  
Vol 2021 (8) ◽  
pp. 6-8
Author(s):  
Takeshi Yamada ◽  
Yuya Arakawa
Keyword(s):  
T Cells ◽  
T Cell ◽  
Energy Metabolism ◽  
T Cell Differentiation ◽  
Glutamine Metabolism ◽  
T Cell Exhaustion ◽  
Epigenetic Changes ◽  
Cell Exhaustion ◽  
Epigenetic Control ◽  
Intracellular Energy

Adoptive immunotherapy can be used to treat intractable cancers but this involves taking T cells from a patient and growing them in a laboratory and, once outside the body, the T cells can fall into a state of exhaustion. This is a barrier that Professor Takeshi Yamada, Department of Medical Technology, Immunology, Ehime Prefectural University of Health Sciences, Japan, is seeking to overcome. His work involves establishing a better understanding of the mechanisms of T cell exhaustion, which are currently not well known. Yamada and his team are focusing on intracellular energy metabolism and epigenetic control in mouse models with a view to finding a way to inhibit T cell exhaustion. The researchers are developing protocols to improve T cell function for immunotherapy by controlling epigenetic changes involved in glutamine metabolism, which induces T cell exhaustion. As previous research has focused on activating and proliferating tumour-specific T cells, Yamada's approach, with a focus on epigenetic control, is novel. The team is interested in T cell differentiation and its links to T cell exhaustion and so they are exploring the mechanism of T cell differentiation via intracellular energy metabolism and epigenetic changes and how this can impact on exhaustion. The researchers previously clarified that the enhancement of glutamine metabolism that occurs during the activation of T cell cultures causes epigenetic changes that induce T cell exhaustion and are expanding on this finding in order to develop a method to suppress T cell exhaustion via epigenetic control.

Metformin Collaborates With PINK1/Mfn2 Overexpression Prevented Isoproterenol-Induced Cardiomyocyte Injury By Improving Mitochondrial Function

2021 ◽  
Author(s):  
Zhuang Ma ◽  
Zuheng Liu ◽  
Yuting Xue ◽  
Hao Zhang ◽  
Wenjun Xiong ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Energy Metabolism ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Membrane ◽  
Mitochondrial Morphology ◽  
Dependent Manner ◽  
Combination Strategy ◽  
Mitochondrial Energy Metabolism ◽  
Atp Production

Abstract Background: Both mitochondrial quality control and energy metabolism are critical in maintaining the physiological function of cardiomyocytes. Previous studies indicated that PGC-1α is a transcription co-activator in promoting mitochondrial energy metabolism which would be beneficial for cardiomyocytes. However, PGC-1α overexpression in heart tissues could also result in the development of cardiomyopathy. This discrepancy in vivo and in vitro might be due to neglecting the elimination of damaged mitochondrial. Thus, an integration strategy of mitochondrial biogenesis and mitophagy might be beneficial.Methods: We studied the function of PINK1 in mitophagy in isoproterenol (Iso)-induced cardiomyocyte injury. Adenovirus was used to provoke an overexpression of the PINK1/Mfn2 protein. Mitochondrial morphology was examined via electron microscopy and confocal microscopy. Cardiomyocytes injury were measured by mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and apoptosis. Metformin was used to increase mitochondrial biogenesis, the level of which was detected via immunoblotting. Additionally, mitochondrial respiratory function was measured by ATP production and oxygen consumption rate (OCR). Results: Cardiomyocytes treated with Iso had high levels of PINK1 and low levels of Mfn2 in a time-dependent manner. PINK1 overexpression promoted mitophagy, alleviated Iso-induced reduction in MMP, reduced ROS production and the apoptotic rate. In addition to increasing mitophagy, metformin could promote mitochondrial biogenensis and the overexpression of Mfn2 induce mitochondrial fusion. Moreover, metformin treatment and PINK1/Mfn2 overexpression reduced the mitochondrial dysfunction by inhibiting the generation of ROS, and leading to an increase in both ATP production and mitochondrial membrane potential in Iso-induced cardiomyocytes injury. Conclusion: Our findings indicate that a combination strategy may help ameliorate myocardial injury through mitophagy and mitochondrial biogenesis.

Low glucose and high pyruvate reduce the production of 2-oxoaldehydes, improving mitochondrial efficiency, redox regulation and stallion sperm function

2021 ◽  
Author(s):  
J M Ortiz-Rodríguez ◽  
F E Martín-Cano ◽  
G Gaitskell-Phillips ◽  
A Silva ◽  
C Ortega-Ferrusola ◽  
...  
Keyword(s):  
Redox Regulation ◽  
Krebs Cycle ◽  
Tca Cycle ◽  
Mitochondrial Activity ◽  
Atp Production ◽  
Transport Chain ◽  
Low Glucose ◽  
Mitochondrial Efficiency ◽  
Metabolic Strategies ◽  
Go Terms

Abstract Energy metabolism in spermatozoa is complex and involves the metabolism of carbohydrate fatty acids and amino acids. The ATP produced in the electron transport chain (ETC) in the mitochondria appears to be crucial for both sperm motility and maintaining viability, while glycolytic enzymes in the flagella may contribute to ATP production to sustain motility and velocity. Stallion spermatozoa seemingly use diverse metabolic strategies, and in this regard, a study of the metabolic proteome showed that gene ontology (GO) terms and Reactome pathways related to pyruvate metabolism and the Krebs cycle were predominant. Following this, the hypothesis that low glucose concentrations can provide sufficient support for motility and velocity, and thus glucose concentration can be significantly reduced in the medium, was tested. Aliquots of stallion semen in four different media were stored for 48 h at 18°C; a commercial extender containing 67 mM glucose was used as a control. Stallion spermatozoa stored in media with low glucose (1 mM) and high pyruvate (10 mM) (LG-HP) sustained better motility and velocities than those stored in the commercial extender formulated with very high glucose (61.7 ± 1.2% in INRA 96 vs 76.2 ± 1.0% in LG-HP media after 48 h of incubation at 18°C P < 0.0001). Moreover, mitochondrial activity was superior in LG-HP extenders (24.1 ± 1.8% in INRA 96 vs 51.1 ± 0.7% in LG-HP of spermatozoa with active mitochondria after 48 h of storage at 18°C P < 0.0001). Low glucose concentrations may permit more efficient sperm metabolism and redox regulation when substrates for an efficient TCA cycle are provided. The improvement seen using low glucose extenders is due to reductions in the levels of glyoxal and methylglyoxal, 2-oxoaldehydes formed during glycolysis; these compounds are potent electrophiles able to react with proteins, lipids and DNA, causing sperm damage.

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