Quantitative importance of the pentose phosphate pathway determined by incorporation of 13C from [2-13C]- and [3-13C]glucose into TCA cycle intermediates and neurotransmitter amino acids in functionally intact neurons.
The brain is highly susceptible to oxidative injury, and the pentose phosphate pathway (PPP) has been shown to be affected by pathological conditions, such as Alzheimer's disease and traumatic brain injury. While this pathway has been investigated in the intact brain and in astrocytes, little is known about the PPP in neurons. The activity of the PPP was quantified in cultured cerebral cortical and cerebellar neurons after incubation in the presence of [2-(13)C]glucose or [3-(13)C]glucose. The activity of the PPP was several fold lower than glycolysis in both types of neurons. While metabolism of (13)C-labeled glucose via the PPP does not appear to contribute to the production of releasable lactate, it contributes to labeling of tricarboxylic acid (TCA) cycle intermediates and related amino acids. Based on glutamate isotopomers, it was calculated that PPP activity accounts for ~6% of glucose metabolism in cortical neurons and ~4% in cerebellar neurons. This is the first demonstration that pyruvate generated from glucose via the PPP contributes to the synthesis of acetyl CoA for oxidation in the TCA cycle. Moreover, the fact that (13)C labeling from glucose is incorporated into glutamate proves that both the oxidative and the nonoxidative stages of the PPP are active in neurons.
Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.
Eva M F
EM
Brekke
Anne B
AB
Walls
Arne
A
Schousboe
Helle S
HS
Waagepetersen
Ursula
U
Sonnewald
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002247:Carbon Isotopes; D002478:Cells, Cultured; D002952:Citric Acid Cycle / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000502:physiology*; D011247:Pregnancy; D019289:Pyruvic Acid / Q000378:metabolism
D000596:Amino Acids; D002247:Carbon Isotopes; D018377:Neurotransmitter Agents; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D005947:Glucose