Underestimation of the Pentose—Phosphate Pathway in Intact Primary Neurons as Revealed by Metabolic Flux Analysis
Open accessAbstract
The rates of glucose oxidized at glycolysis and pentose–phosphate pathway (PPP) in neurons are controversial. Using [3- 3 H]-, [1- 14 C]-, and [6- 14 C]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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The rate of glycolysis, determined by metabolic flux analysis, is significantly higher in primary astrocytes than in cultured neurons.
“The rate of glycolysis, determined by metabolic flux analysis, was significantly higher in primary astrocytes than in cultured neurons [6].”
From Proliferating Astrocytes in Primary Culture Do Not Depend upon Mitochondrial Respiratory Complex I Activity or Oxidative Phosphorylation (2023) · cites this paper as [6]
The Results and Discussion report a glycolytic rate of about 1.2 nmol/min/mg protein in cultured neurons versus 3.14 ± 0.27 in attached astrocytes measured using the same protocol. The paper calls the neuronal rate 'considerably lower,' but does not report a statistical significance test for that comparison, so the claim's 'significantly higher' qualifier is not established. (LLM, conf=0.83)
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- Authors
- Rodriguez-Rodriguez, P., Fernandez, E., & Bolaños, J. P.
- Affiliations
- Institute of Functional Biology and Genomics (IBFG), University of Salamanca-CSIC, Salamanca, Spain
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Bolaños, Juan P
- ORCID
- Bolaños, Juan P
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2013-09-25
- Volume
- 33
- Issue
- 12
- Pages
- 1843-1845
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC3851909
- OpenAlex
- W2023779632
- Cited by
- 53
- References
- 0
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 7 · 2014: 3
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- pentose phosphate pathway, glycolysis, glucose metabolism, primary neurons, cortical neurons, metabolic flux analysis, glucose-6-phosphate dehydrogenase, phosphoglucose isomerase, fructose-6-phosphate
- MeSH terms
- Animals, Carbon Isotopes, Cells, Cultured, Fructosephosphates, Glucose, Glycolysis, Neurons, Pentose Phosphate Pathway, Rats, Wistar, Rats, Metabolic Flux Analysis
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