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Figure 3. Expanded 13C MR spectrum of Canavan's patient. (A) baseline; (B) 13C enriched (120-140 min). Note labeling of Asp not detectable in the baseline and the significant labeling of NAA in carbons 2,3 (shaded).

Metabolic modeling of NAA-synthesis: Figure 2 explains the very simple theory behind the use of 13C glucose to observed NAA-synthesis. 1-13C glucose enters the brain and then, as pyruvate enters the mitochondrion of the neuron, oxidation through the mitochondrial enzyme pyruvate dehydrogenase (PDH) results in conversion to the 2 carbon fragment acetyl-coenzyme A (Figure 2A). After traversing the Krebs cycle (1st turn), 13C atoms appear in oxaloacetate, before rejoining the Krebs cycle (2nd turn). Transaminase activity ensures that 13C aspartate is formed. Incorporation of 13C aspartate into specific carbon atoms of NAA also occurs within the neuronal mitochondrion, as shown (Figure 2 B). 13C MRS readily distinguishes carbon 2,3 of aspartate and of NAA, so that the rate of NAA-synthesis can be derived as shown in Equation 1. For further details and validation of this method please see Moreno et al..

NAA-synthesis was determined in the brains of 4 normal control subjects (5 examinations) and in 3 children with enzymically verified Canavan's Disease, with the informed consent of parents, the FDA (IND 56,510) and the Internal Review Board of Huntington Hospital.

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