Direct determination of the N-acetyl-L-aspartate synthesis rate in the human brain by C-13 MRS and [1-C-13]glucose infusion

A non-invasive C-13 magnetic resonance spectroscopy (MRS) technique is desc ribed for the determination of the N-acetyl-L-aspartate (NAA) synthesis rat e, 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), VNAA 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 di sease. The present result is consistent with the regulation of NAA synthesi s by the activity of a single enzyme, L-aspartate-N-acetyltransferase, in v ivo, and with its control in Canavan disease by limited substrate supply an d/or product inhibition. The C-13 MRS technique provides the means for furt her determination of abnormal rates of neuronal NAA synthesis among neurolo gical disorders in which low cerebral [NAA] has been identified.