Wnt5a Increases the Glycolytic Rate and the Activity of the Pentose Phosphate Pathway in Cortical Neurons

In the last few years, several reports have proposed that Wnt signaling is a general metabolic regulator, suggesting a role for this pathway in the control of metabolic flux. Wnt signaling is critical for several neuronal functions, but little is known about the correlation between this pathway and energy metabolism. The brain has a high demand for glucose, which is mainly used for energy production. Neurons use energy for highly specific processes that require a high energy level, such as maintaining the electrical potential and synthesizing neurotransmitters. Moreover, an important metabolic impairment has been described in all neurodegenerative disorders. Despite the key role of glucose metabolism in the brain, little is known about the cellular pathways involved in regulating this process. We report here that Wnt5a induces an increase in glucose uptake and glycolytic rate and an increase in the activity of the pentose phosphate pathway; the effects of Wnt5a require the intracellular generation of nitric oxide. Our data suggest that Wnt signaling stimulates neuronal glucose metabolism, an effect that could be important for the reported neuroprotective role of Wnt signaling in neurodegenerative disorders.

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Evidence of the Role of Omega-3 Polyunsaturated Fatty Acids in Brain Glucose Metabolism

Nutrients ◽

10.3390/nu12051382 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1382

Author(s):

Fabien Pifferi ◽

Stephen C. Cunnane ◽

Philippe Guesnet

Keyword(s):

Fatty Acids ◽

Glucose Metabolism ◽

Polyunsaturated Fatty Acids ◽

Brain Function ◽

High Energy ◽

Brain Glucose ◽

Brain Glucose Metabolism ◽

Age Related ◽

The Brain

In mammals, brain function, particularly neuronal activity, has high energy needs. When glucose is supplemented by alternative oxidative substrates under different physiological conditions, these fuels do not fully replace the functions fulfilled by glucose. Thus, it is of major importance that the brain is almost continuously supplied with glucose from the circulation. Numerous studies describe the decrease in brain glucose metabolism during healthy or pathological ageing, but little is known about the mechanisms that cause such impairment. Although it appears difficult to determine the exact role of brain glucose hypometabolism during healthy ageing or during age-related neurodegenerative diseases such as Alzheimer’s disease, uninterrupted glucose supply to the brain is still of major importance for proper brain function. Interestingly, a body of evidence suggests that dietary n-3 polyunsaturated fatty acids (PUFAs) might play significant roles in brain glucose regulation. Thus, the goal of the present review is to summarize this evidence and address the role of n-3 PUFAs in brain energy metabolism. Taken together, these data suggest that ensuring an adequate dietary supply of n-3 PUFAs could constitute an essential aspect of a promising strategy to promote optimal brain function during both healthy and pathological ageing.

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Role of the pentose phosphate pathway and the Entner–Doudoroff pathway in glucose metabolism of Gluconobacter oxydans 621H

Applied Microbiology and Biotechnology ◽

10.1007/s00253-013-4707-2 ◽

2013 ◽

Vol 97 (10) ◽

pp. 4315-4323 ◽

Cited By ~ 25

Author(s):

Janine Richhardt ◽

Stephanie Bringer ◽

Michael Bott

Keyword(s):

Glucose Metabolism ◽

Pentose Phosphate Pathway ◽

Gluconobacter Oxydans ◽

Pentose Phosphate

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Metabolic flux pattern of glucose utilization by Xanthomonas campestris pv. campestris: prevalent role of the Entner–Doudoroff pathway and minor fluxes through the pentose phosphate pathway and glycolysis

Molecular BioSystems ◽

10.1039/c4mb00198b ◽

2014 ◽

Vol 10 (10) ◽

pp. 2663-2676 ◽

Cited By ~ 19

Author(s):

Sarah Schatschneider ◽

Claudia Huber ◽

Heiko Neuweger ◽

Tony Francis Watt ◽

Alfred Pühler ◽

...

Keyword(s):

Pentose Phosphate Pathway ◽

Xanthomonas Campestris ◽

Metabolic Flux ◽

Glucose Utilization ◽

Pentose Phosphate ◽

Xanthomonas Campestris Pv Campestris

Complex metabolic flux pattern ofX. campestris.

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Underestimation of the Pentose–Phosphate Pathway in Intact Primary Neurons as Revealed by Metabolic Flux Analysis

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.168 ◽

2013 ◽

Vol 33 (12) ◽

pp. 1843-1845 ◽

Cited By ~ 20

Author(s):

Patricia Rodriguez-Rodriguez ◽

Emilio Fernandez ◽

Juan P Bolaños

Keyword(s):

Pentose Phosphate Pathway ◽

Metabolic Flux ◽

Pentose Phosphate ◽

Flux Analysis ◽

Primary Neurons ◽

Rate Limiting Step ◽

Limiting Step ◽

Total Glucose ◽

Rate Limiting ◽

Glycolytic Rate

The rates of glucose oxidized at glycolysis and pentose–phosphate pathway (PPP) in neurons are controversial. Using [3-3H]-, [1-14C]-, and [6-14C]glucose to estimate fluxes through these pathways in resting, intact rat cortical primary neurons, we found that the rate of glucose oxidized through PPP was, apparently, ∼14% of total glucose metabolized. However, inhibition of PPP rate-limiting step, glucose-6-phosphate (G6P) dehydrogenase, increased approximately twofold the glycolytic rate; and, knockdown of phosphoglucose isomerase increased ∼1.8-fold the PPP rate. Thus, in neurons, a considerable fraction of fructose-6-phosphate returning from the PPP contributes to the G6P pool that re-enters PPP, largely underestimating its flux.

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Disturbances in the glucose metabolism in the brain: the role of stress and high-fat diet

10.26226/morressier.5b681761b56e9b005965c76f ◽

2018 ◽

Author(s):

Katarzyna Glombik

Keyword(s):

Glucose Metabolism ◽

High Fat Diet ◽

High Fat ◽

The Brain

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Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666190916141934 ◽

2019 ◽

Vol 18 (8) ◽

pp. 581-597 ◽

Cited By ~ 1

Author(s):

Ambreen Fatima ◽

Yasir Hasan Siddique

Keyword(s):

Medicinal Plants ◽

Mechanism Of Action ◽

Neurodegenerative Disorders ◽

Treatment Strategies ◽

Dietary Supplementation ◽

Plant Polyphenols ◽

Promising Candidate ◽

Naturally Occurring ◽

The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

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Fine tuning the glycolytic flux ratio of EP-bifido pathway for mevalonate production by enhancing glucose-6-phosphate dehydrogenase (Zwf) and CRISPRi suppressing 6-phosphofructose kinase (PfkA) in Escherichia coli

Microbial Cell Factories ◽

10.1186/s12934-021-01526-1 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Ying Li ◽

He Xian ◽

Ya Xu ◽

Yuan Zhu ◽

Zhijie Sun ◽

...

Keyword(s):

Pentose Phosphate Pathway ◽

Conversion Rate ◽

Metabolic Flux ◽

Flux Ratio ◽

Reducing Power ◽

Pentose Phosphate ◽

Fine Tuning ◽

High Yield ◽

Glycolytic Flux ◽

Acetyl Coa

Abstract Background Natural glycolysis encounters the decarboxylation of glucose partial oxidation product pyruvate into acetyl-CoA, where one-third of the carbon is lost at CO2. We previously constructed a carbon saving pathway, EP-bifido pathway by combining Embden-Meyerhof-Parnas Pathway, Pentose Phosphate Pathway and “bifid shunt”, to generate high yield acetyl-CoA from glucose. However, the carbon conversion rate and reducing power of this pathway was not optimal, the flux ratio of EMP pathway and pentose phosphate pathway (PPP) needs to be precisely and dynamically adjusted to improve the production of mevalonate (MVA). Result Here, we finely tuned the glycolytic flux ratio in two ways. First, we enhanced PPP flux for NADPH supply by replacing the promoter of zwf on the genome with a set of different strength promoters. Compared with the previous EP-bifido strains, the zwf-modified strains showed obvious differences in NADPH, NADH, and ATP synthesis levels. Among them, strain BP10BF accumulated 11.2 g/L of MVA after 72 h of fermentation and the molar conversion rate from glucose reached 62.2%. Second, pfkA was finely down-regulated by the clustered regularly interspaced short palindromic repeats interference (CRISPRi) system. The MVA yield of the regulated strain BiB1F was 8.53 g/L, and the conversion rate from glucose reached 68.7%. Conclusion This is the highest MVA conversion rate reported in shaken flask fermentation. The CRISPRi and promoter fine-tuning provided an effective strategy for metabolic flux redistribution in many metabolic pathways and promotes the chemicals production.

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Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells

Nature Communications ◽

10.1038/s41467-020-20479-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ratnasekhar Ch ◽

Guillaume Rey ◽

Sandipan Ray ◽

Pawan K. Jha ◽

Paul C. Driscoll ◽

...

Keyword(s):

Glucose Metabolism ◽

Red Blood Cells ◽

Blood Cells ◽

Mammalian Cells ◽

Metabolic Flux ◽

Pentose Phosphate ◽

Human Red Blood Cells ◽

Integral Process ◽

Metabolic Oscillations ◽

Human Rbcs

AbstractCircadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.

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