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Assessing the pentose phosphate pathway using [2, 3-13 C2 ]glucose.
Min Hee Lee1, Craig R Malloy1,2,3,4, Ian R Corbin1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
NMR in Biomedicine
|March 30, 2019
Summary
A new tracer, [2,3-13C2]glucose, simplifies the study of the pentose phosphate pathway (PPP). This method accurately measures PPP activity in the liver and heart, and in hepatoma, without needing natural abundance correction.
Area of Science:
- Metabolic pathways
- Biochemistry
- Biophysics
Background:
- The pentose phosphate pathway (PPP) is crucial for biosynthesis, antioxidant defense, and nucleotide synthesis.
- Current tracers like [1,2-13C2]glucose require complex corrections for natural 13C abundance.
- Accurate assessment of PPP activity is vital for understanding cellular metabolism and disease states.
Purpose of the Study:
- To introduce a novel and specific tracer, [2,3-13C2]glucose, for assessing PPP activity.
- To demonstrate the utility of 13C Nuclear Magnetic Resonance (NMR) spectroscopy for analyzing PPP flux.
- To investigate PPP activity in different physiological states and in disease models.
Main Methods:
- Utilized [2,3-13C2]glucose as a tracer for the pentose phosphate pathway.
- Employed 13C NMR spectroscopy to analyze isotopomer distribution in metabolic products, specifically lactate.
- Administered the tracer to rats in fed and fasted states, and in hepatoma models.
Main Results:
- [2,3-13C2]glucose allows for direct and specific detection of PPP activity via [2,3-13C2]lactate.
- Natural 13C abundance correction is unnecessary when using [2,3-13C2]glucose.
- PPP activity was higher in the fed state compared to the fasted state in rat liver and heart.
- Both PPP and glycolysis were significantly elevated in hepatoma compared to normal liver tissue.
Conclusions:
- [2,3-13C2]glucose serves as a specific and simplified tracer for the pentose phosphate pathway.
- 13C NMR analysis with this tracer provides a robust method for assessing PPP flux.
- This approach facilitates the study of PPP regulation in physiological and pathological conditions.
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