scholarly journals Reversed upper glycolysis and rapid activation of oxidative pentose phosphate pathway supports the oxidative burst in neutrophils

2020 ◽  
Author(s):  
Emily C. Britt ◽  
Jing Fan
Keyword(s):  
Glucose Metabolism ◽  
Pentose Phosphate Pathway ◽  
Oxidative Burst ◽  
Mammalian Cells ◽  
White Blood Cells ◽  
Glycolytic Enzyme ◽  
Pentose Phosphate ◽  
Human Neutrophils ◽  
Effector Functions ◽  
Rapid Activation

AbstractNeutrophils are abundant white blood cells at the frontline of innate immunity. Upon stimulation, neutrophils rapidly activate effector functions such as the oxidative burst and neutrophil extracellular traps (NETs) to eliminate pathogens. However, little is known about how neutrophil metabolism powers these functions. Our metabolomic analysis on primary human neutrophils revealed that neutrophil metabolism is rapidly rewired upon pro-inflammatory activation, with particularly profound changes observed in glycolysis and the pentose phosphate pathway (PPP). We found that the stimulation-induced changes in PPP were specifically coupled with the oxidative burst. The oxidative burst requires a large amount of NADPH to fuel superoxide production via NADPH Oxidase (NOX). Isotopic tracing studies revealed that in order to maximize the NADPH yield from glucose metabolism, neutrophils quickly adopt near complete pentose cycle during the oxidative burst. In this metabolic mode, all glucose is shunted into the oxidative PPP, and the resulting pentose-phosphate is recycled back to glucose-6-phosphate, which then re-enters the oxidative PPP. To enable this recycling, net flux through the upper glycolytic enzyme glucose-6-phosphate isomerase (GPI) is completely reversed. This allows oxidative PPP flux in neutrophils to reach greater than two-fold of the glucose uptake rate, far exceeding other known mammalian cells and tissues. Intriguingly, the adoption of this striking metabolic mode is completely dependent on an increased demand for NADPH associated with the oxidative burst, as inhibition of NOX resets stimulated neutrophils to use glycolysis-dominant glucose metabolism, with oxidative PPP flux accounting for less than 10% of glucose metabolism. Together, these data demonstrated that neutrophils have remarkable metabolic flexibility that is essential to enable the rapid activation of their effector functions.Graphic Abstract

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

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.

scholarly journals Insulin stimulates glucose metabolism via the pentose phosphate pathway in Drosophila Kc cells

FEBS Letters ◽  
2003 ◽  
Vol 555 (2) ◽  
pp. 307-310 ◽  
Author(s):  
Rolando B. Ceddia ◽  
George J. Bikopoulos ◽  
Arthur J. Hilliker ◽  
Gary Sweeney
Keyword(s):  
Glucose Metabolism ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate

scholarly journals The Pentose Phosphate Pathway and Pyruvate Carboxylation after Neonatal Hypoxic-Ischemic Brain Injury

2014 ◽  
Vol 34 (4) ◽  
pp. 724-734 ◽  
Author(s):  
Eva MF Brekke ◽  
Tora S Morken ◽  
Marius Widerøe ◽  
Asta K Håberg ◽  
Ann-Mari Brubakk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Glucose Metabolism ◽  
Pentose Phosphate Pathway ◽  
De Novo ◽  
Pentose Phosphate ◽  
Adult Brain ◽  
Resonance Spectroscopy ◽  
Neonatal Brain ◽  
Artery Ligation ◽  
Pyruvate Carboxylation

The neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance to limit the injury. Furthermore, in the neonatal brain, neurons depend on de novo synthesis of neurotransmitters via pyruvate carboxylase (PC) in astrocytes to increase neurotransmitter pools. In the adult brain, PPP activity increases in response to various injuries while pyruvate carboxylation is reduced after ischemia. However, little is known about the response of these pathways after neonatal hypoxia-ischemia (HI). To this end, 7-day-old rats were subjected to unilateral carotid artery ligation followed by hypoxia. Animals were injected with [1,2-13C]glucose during the recovery phase and extracts of cerebral hemispheres ipsi- and contralateral to the operation were analyzed using 1H- and 13C-NMR (nuclear magnetic resonance) spectroscopy and high-performance liquid chromatography (HPLC). After HI, glucose levels were increased and there was evidence of mitochondrial hypometabolism in both hemispheres. Moreover, metabolism via PPP was reduced bilaterally. Ipsilateral glucose metabolism via PC was reduced, but PC activity was relatively preserved compared with glucose metabolism via pyruvate dehydrogenase. The observed reduction in PPP activity after HI may contribute to the increased susceptibility of the neonatal brain to oxidative stress.

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

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Pedro Cisternas ◽  
Paulina Salazar ◽  
Carmen Silva-Álvarez ◽  
L. Felipe Barros ◽  
Nibaldo C. Inestrosa
Keyword(s):  
Glucose Metabolism ◽  
Wnt Signaling ◽  
Pentose Phosphate Pathway ◽  
Neurodegenerative Disorders ◽  
Metabolic Flux ◽  
High Energy ◽  
Pentose Phosphate ◽  
The Brain ◽  
Glycolytic Rate

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.

Pathways of glucose catabolism in Mycobacterium smegmatis

1976 ◽  
Vol 22 (9) ◽  
pp. 1374-1380 ◽  
Author(s):  
N. Jayanthi Bai ◽  
M. Ramachandra Pai ◽  
P. Suryanarayana Murthy ◽  
T. A. Venkitasubramanian
Keyword(s):  
Glucose Metabolism ◽  
Carbon Source ◽  
Pentose Phosphate Pathway ◽  
Mycobacterium Smegmatis ◽  
Pentose Phosphate ◽  
Minor Role ◽  
Key Enzymes ◽  
Glucose Catabolism ◽  
A Minor ◽  
Cells Cultured

Glucose metabolism in Mycobacterium smegmatis was investigated by the radiorespirometric method and by assaying for key enzymes of the major energy-yielding pathways. Glucose is oxidized in this organism mainly through the Embden–Meyerhof–Parnas pathway, irrespective of the carbon source used for growth. The pentose phosphate pathway plays only a minor role and its extent depends on the carbon source used for growth. Enzymes of glycolytic and oxidative pathways were detected in cells grown on glucose, glycerol, or pyruvate but enzymes of the Entner–Doudoroff pathway could be detected only in glucose-grown cells. Labeled acetate is utilized by cells cultured on glucose, glycerol, and pyruvate. In all cases more of C1 of acetate was converted to CO2 while incorporation into cellular constituents was maximum from C2 of acetate.

Localization of an Infectious Lesion and Glucose Metabolism via the Pentose Phosphate Pathway

Nature ◽  
1964 ◽  
Vol 201 (4921) ◽  
pp. 825-827 ◽  
Author(s):  
PETER BEACONSFIELD ◽  
AMILCARE CARPI
Keyword(s):  
Glucose Metabolism ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate
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