Direct determination of the N-acetyl-L-aspartate synthesis rate in the human brain by (13)C MRS and [1-(13)C]glucose infusion.
A non-invasive (13)C magnetic resonance spectroscopy (MRS) technique is described for the determination of the N-acetyl-L-aspartate (NAA) synthesis rate, V(NAA), in the human brain in vivo. In controls, the mean V(NAA) was 9.2 +/- 3.9 nmol/min/g. In Canavan disease, where [NAA] is increased (p < 0.001) and [aspartate] is deceased (p < 0.001), V(NAA) was significantly reduced to 3.6 +/- 0.1 nmol/min/g (p < 0.001). These rates are in close agreement with the activity of the biosynthetic enzyme measured in vitro in animals, and with the rate of urinary excretion of NAA in human subjects with Canavan disease. The present result is consistent with the regulation of NAA synthesis by the activity of a single enzyme, L-aspartate-N-acetyltransferase, in vivo, and with its control in Canavan disease by limited substrate supply and/or product inhibition. The (13)C MRS technique provides the means for further determination of abnormal rates of neuronal NAA synthesis among neurological disorders in which low cerebral [NAA] has been identified.
Huntington Medical Research Institutes, Pasadena, California 91105, USA.
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Moreno
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BD
Ross
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Blüml
D000328:Adult; D000581:Amidohydrolases / Q000172:deficiency / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D017825:Canavan Disease / Q000175:diagnosis* / Q000378:metabolism; D002247:Carbon Isotopes / Q000032:analysis; D002675:Child, Preschool; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D007441:Intubation, Gastrointestinal; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011237:Predictive Value of Tests
D002247:Carbon Isotopes; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D000581:Amidohydrolases; C019751:aspartoacylase; D005947:Glucose