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Cited by 77Diet and metabolism studiesEpilepsy research and treatmentBiochemical Acid Research Studies

Impairments in oxidative glucose metabolism in epilepsy and metabolic treatments thereof

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McDonald, Tanya, Puchowicz, Michelle, Borges, Karin·2018·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2018.00274PMC PMC6127311
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Abstract

There is mounting evidence that oxidative glucose metabolism is impaired in epilepsy and recent work has further characterized the metabolic mechanisms involved. In healthy people eating a traditional diet, including carbohydrates, fats and protein, the major energy substrate in brain is glucose. Cytosolic glucose metabolism generates small amounts of energy, but oxidative glucose metabolism in the mitochondria generates most ATP, in addition to biosynthetic precursors in cells. Energy is crucial for the brain to signal "normally," while loss of energy can contribute to seizure generation by destabilizing membrane potentials and signaling in the chronic epileptic brain. Here we summarize the known biochemical mechanisms that contribute to the disturbance in oxidative glucose metabolism in epilepsy, including decreases in glucose transport, reduced activity of particular steps in the oxidative metabolism of glucose such as pyruvate dehydrogenase activity, and increased anaplerotic need. This knowledge justifies the use of alternative brain fuels as sources of energy, such as ketones, TCA cycle intermediates and precursors as well as even medium chain fatty acids and triheptanoin.

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  • During epileptic seizures, the lactate concentration rises whereas the pyruvate concentration falls via LDH, resulting in decreased use of pyruvate in TCA cycle and oxidative phosphorylation.

    “During epileptic seizures, the lactate concentration rises whereas the pyruvate concentration falls via LDH, resulting in decreased use of pyruvate in TCA cycle and oxidative phosphorylation (McDonald et al., 2018).”

    From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as McDonald et al., 2018

    The “Changes in Glucose Transport and Glycolysis Between and After Seizures” section supports elevated lactate during seizures, but says that the cellular pyruvate pool increases, driving LDH to convert pyruvate to lactate—not that pyruvate concentration falls. The paper also suggests reduced pyruvate entry into the TCA cycle, but does not present it as a consequence of falling pyruvate concentration. Page numbers were not supplied in our copy. (LLM, conf=0.88)

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  • Cerebral glucose hypometabolism occurs in both the early stage of AD and epilepsy.

    “Importantly, cerebral glucose hypometabolism occurs in both the early stage of AD (Christian et al., 2020; Yamazaki et al., 2019) and epilepsy (McDonald et al., 2018; Patel, 2018).”

    From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as McDonald et al., 2018

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Cited by

Sorted by citations

Authors
McDonald, T., Puchowicz, M., & Borges, K.
Affiliations
  • The University of Queensland (AU)
  • University of Tennessee Health Science Center (US)
Corresponding author
Borges, Karin
ORCID
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2018-08-31
Volume
12
Pages
274-274
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2018.00274
PMC
PMC6127311
OpenAlex
W2888815451
Cited by
77
References
5
Citations by year
2026: 9 · 2025: 11 · 2024: 6 · 2023: 8 · 2022: 16 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 1
FWCI
0.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Physiology › Diet and metabolism studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
Keywords
glucose oxidation, epilepsy, mitochondrial bioenergetics, brain energy metabolism, glucose transport, pyruvate dehydrogenase, anaplerosis, ketones, TCA cycle intermediates, medium-chain fatty acids, triheptanoin, metabolic therapy, seizure generation, ATP production

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