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Direct determination of the N ‐acetyl‐ l ‐aspartate synthesis rate in the human brain by 13 C MRS and [1‐ 13 C]glucose infusion
Author(s) -
Moreno Angel,
Ross Brian D.,
Blüml Stefan
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00282.x
Subject(s) - in vivo , acetyl coa , enzyme , chemistry , specific activity , substrate (aquarium) , enzyme assay , human brain , endocrinology , n acetyltransferase , biochemistry , medicine , biology , acetylation , ecology , microbiology and biotechnology , neuroscience , gene
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.