INHIBITION OF N-ACETYLASPARTATE PRODUCTION - IMPLICATIONS FOR H-1 MRSSTUDIES IN-VIVO

THE effect of specific irreversible inhibitors of complexes I, III, IV and V of the mitochondrial respiratory chain, (rotenone, myxothiazol, cyanide and oligomycin, respectively) on mitochondrial N-acetylaspart ate production, and its relationship to oxidative phosphorylation (ATP production and oxygen consumption) were investigated in isolated rat brain mitochondria. Mitochondrial N-acetylaspartate production, ATP pr oduction and oxygen consumption were all significantly decreased in th e presence of each of the inhibitors used compared with control incuba tions, and correlated positively with each other. It is postulated tha t decreased N-acetylaspartate levels seen in disease states by H-1 NMR spectroscopy in vivo may reflect primarily an impaired mitochondrial energy production rather than neuronal cell loss.