Impairments in Oxidative Glucose Metabolism in Epilepsy and Metabolic Treatments Thereof

Frontiers in Cellular Neuroscience
Tanya S McDonaldKarin Borges

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.

References

Jan 1, 1979·Advances in Enzymology and Related Areas of Molecular Biology·K Uyeda
Jul 22, 1975·Biochemical and Biophysical Research Communications·F H PettitL J Reed
Jan 1, 1976·Reviews of Physiology, Biochemistry and Pharmacology·E Hofmann
May 1, 1975·Journal of Neurochemistry·T E DuffyF Plum
Apr 7, 1992·Biochimica Et Biophysica Acta·M A SciamannaC P Lee
Nov 1, 1990·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M S Patel, T E Roche
Dec 1, 1986·Archives of Disease in Childhood·M A SillsD Haidukewych
Oct 1, 1967·The Journal of Clinical Investigation·O E OwenG F Cahill
Jan 1, 1983·Reviews of Physiology, Biochemistry and Pharmacology·O H Wieland
Mar 15, 1981·The Biochemical Journal·E M NuutinenI E Hassinen
May 14, 1993·Biochemical and Biophysical Research Communications·A M BrantG W Gould
Jun 19, 1998·Brain Research·S J VannucciI A Simpson
Nov 27, 1998·European Journal of Pharmacology·E M UrbanskaW A Turski
Mar 21, 2002·Epilepsy Research·Hannah R CockMatthew C Walker
Jun 28, 2002·The Journal of Biological Chemistry·Oliver E OwenRichard W Hanson
Oct 22, 2002·American Journal of Physiology. Endocrinology and Metabolism·Wenjun Z MartiniHenri Brunengraber
May 20, 2003·Current Opinion in Plant Biology·Nicholas J Kruger, Antje von Schaewen
Jun 25, 2003·Experimental Neurology·Karin BorgesRaymond Dingledine
May 12, 2004·Current Opinion in Plant Biology·Alisdair R FernieLee J Sweetlove
Jul 30, 2004·Brain : a Journal of Neurology·R P CarneM J Cook
Jan 26, 2005·Annals of Neurology·Idil CavusWalid M Abi-Saab
Mar 23, 2005·Molecular Genetics and Metabolism·Fanny MochelJean-Marie Saudubray
May 20, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Torun M MeløUrsula Sonnewald
May 18, 2006·American Journal of Physiology. Endocrinology and Metabolism·Renée P KinmanHenri Brunengraber
Jun 10, 2006·Journal of Inherited Metabolic Disease·Henri Brunengraber, Charles R Roe
Aug 29, 2006·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jayatri Das

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Citations

Feb 23, 2019·Science Translational Medicine·Vikram JakkamsettiJuan M Pascual
Dec 21, 2019·Journal of the American College of Nutrition·Ramona De AmicisSimona Bertoli
Mar 4, 2020·Brain Sciences·Raluca Maria CosteaBogdan Neamtu
Nov 30, 2019·Journal of Inherited Metabolic Disease·Zeinab Wehbe, Sara Tucci
Mar 21, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Tanya McDonaldKarin Borges
Jul 23, 2020·Nature Metabolism·Janelle S Ayres
Jul 28, 2020·Nature Reviews. Drug Discovery·Stephen C CunnaneMark J Millan
Jun 18, 2020·International Journal of Tryptophan Research : IJTR·David B RamsdenAdrian C Williams
Oct 7, 2020·Metabolomics : Official Journal of the Metabolomic Society·Alicia JohnsonJiri Adamec
Mar 30, 2021·Mitochondrion·Shareen SinghRupinder Kaur
Jun 23, 2021·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·An BuckinxIlse Smolders
Jul 6, 2021·Epilepsia·Nina MiljanovicHeidrun Potschka
Oct 16, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Shareen Singh, Thakur Gurjeet Singh

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