Figure 4. Demonstration of in vivo C aspartate and NAA formation in human brain.

3.2. NAA-Synthesis in Children with Canavan's Disease

Net NAA-synthesis was readily measured in children with Canavan's Disease and was reduced by 60% (3.6 nanomoles/minute/gram brain) (Table 2). It is interesting to speculate on a mechanism for this somewhat surprising finding - whether NAA-synthetase is subject to end-product inhibition by the large accumulation of NAA, or limited by substrate supply of its precursor, aspartate? The early in vitro study in rodent brain suggested the former to be more likely, since NAA-synthetase was strongly subject to end-product inhibition9.

Table 2. Regulation of cerebral NAA in Canavan's Disease. NAA synthesis rate is decreased, despite increased NAA concentration. Aspartate and glutamate are reduced. The hypotheses are that NAA synthetase is subject to feed-back inhibition, or that NAA synthetase is substrate limited.

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