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
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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. / Brekke, Eva Marie; Walls, Anne Byriel; Schousboe, Arne; Waagepetersen, Helle S.; Sonnewald, Ursula.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 32, No. 9, 2012, p. 1788-1799.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - 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
AU - Brekke, Eva Marie
AU - Walls, Anne Byriel
AU - Schousboe, Arne
AU - Waagepetersen, Helle S.
AU - Sonnewald, Ursula
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Acetyl Coenzyme A
KW - Amino Acids
KW - Animals
KW - Carbon Isotopes
KW - Cells, Cultured
KW - Citric Acid Cycle
KW - Female
KW - Glucose
KW - Glycolysis
KW - Magnetic Resonance Spectroscopy
KW - Mice
KW - Neurons
KW - Neurotransmitter Agents
KW - Oxidation-Reduction
KW - Pentose Phosphate Pathway
KW - Pregnancy
KW - Pyruvic Acid
U2 - 10.1038/jcbfm.2012.85
DO - 10.1038/jcbfm.2012.85
M3 - Journal article
C2 - 22714050
VL - 32
SP - 1788
EP - 1799
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 9
ER -
ID: 45884926