Impairments in oxidative glucose metabolism in epilepsy and metabolic treatments thereof

Tanya McDonald, Michelle Puchowicz, Karin Borges

Research output: Contribution to journalReview article

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article number274
JournalFrontiers in Cellular Neuroscience
Volume12
DOIs
StatePublished - Aug 31 2018

Fingerprint

Epilepsy
Glucose
Brain
Ketones
Pyruvic Acid
Membrane Potentials
Mitochondria
Oxidoreductases
Seizures
Fatty Acids
Adenosine Triphosphate
Fats
Carbohydrates
Diet
Proteins

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Impairments in oxidative glucose metabolism in epilepsy and metabolic treatments thereof. / McDonald, Tanya; Puchowicz, Michelle; Borges, Karin.

In: Frontiers in Cellular Neuroscience, Vol. 12, 274, 31.08.2018.

Research output: Contribution to journalReview article

@article{d89ad63fd7704e03b4612b03e6383663,
title = "Impairments in oxidative glucose metabolism in epilepsy and metabolic treatments thereof",
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.",
author = "Tanya McDonald and Michelle Puchowicz and Karin Borges",
year = "2018",
month = "8",
day = "31",
doi = "10.3389/fncel.2018.00274",
language = "English (US)",
volume = "12",
journal = "Frontiers in Cellular Neuroscience",
issn = "1662-5102",
publisher = "Frontiers Research Foundation",

}

TY - JOUR

T1 - Impairments in oxidative glucose metabolism in epilepsy and metabolic treatments thereof

AU - McDonald, Tanya

AU - Puchowicz, Michelle

AU - Borges, Karin

PY - 2018/8/31

Y1 - 2018/8/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85053334645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053334645&partnerID=8YFLogxK

U2 - 10.3389/fncel.2018.00274

DO - 10.3389/fncel.2018.00274

M3 - Review article

VL - 12

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

SN - 1662-5102

M1 - 274

ER -