Metabolism of trifluorothymidine (TFT) and its transport across the blood-brain barrier (BBB) has been measured quantitatively in rats by fluorine-19 nuclear magnetic resonance spectroscopy ( 19 F NMR). It is demonstrated that TFT crosses the BBB in micromolar quantities and is metabolized in brain
Quantitative 13C NMR studies of metabolic compartmentation in the adult mammalian brain
✍ Scribed by Fátima Cruz; Sebastián Cerdán
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 494 KB
- Volume
- 12
- Category
- Article
- ISSN
- 0952-3480
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✦ Synopsis
We review the information obtained by 13 C NMR methods on the metabolic compartmentation of the adult mammalian brain with emphasis on its quantitative aspects. Classical radiotracer evidence and more recent 13 C NMR results support the presence in the brain of at least two glutamate pools, small and large, associated with two kinetically different tricarboxylic acid cycles localized in glia and neurons, respectively. Neuronal and glial cycles interact closely, utilizing common substrates like glucose and oxygen and exchanging a variety of metabolites including glutamate, glutamine and GABA. A model for the cerebral metabolism of (1,2À 13 C 2 ) acetate has made it possible to calculate fluxes through both cycles and evaluate the exchanges of glutamate, glutamine and GABA under different physiopathological conditions. Calculated flux values through the neuronal and glial tricarboxylic acid cycles are 1.0 and 0.4 mmol/min g, respectively. In the adult normoxic brain, the small and large glutamate pools account for approximately 10% and 90% of cerebral glutamate with estimated turnover times of 1.25 and 5.8/min, respectively. Net transfers of neuronal glutamate and GABA to the glial compartment are calculated to be 0.1 and 0.04 mmol/min g while transfer of glial glutamine to the neuronal compartment is estimated as 0.1 mmol/min g. Pyruvate recycling in the adult brain occurs mainly in the synaptic terminals with a calculated flux of 0.3 mmol/min g. These flux values are altered severely in pathological states such as hypothyroidism or ischemia.
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