Ly. Zang et Hp. Misra, ACETYLCHOLINESTERASE INHIBITION BY 1-METHYL-4 PHENYLPYRIDINIUM ION, ABIOACTIVATED METABOLITE OF MPTP, Molecular and cellular biochemistry, 126(2), 1993, pp. 93-100
The effect of the neurotoxicant, 1-methyl-4-phenylpyridinium ion (MPP(
+)) on acetylcholinesterase (AchE) activity was investigated. The MPP(
+) was found to inactivate the enzyme in a dose dependent manner. The
kinetic parameter, K-m for the substrate (acetylthiocholine), was foun
d to be 0.216 mM and Ki for MPP(+) for the inactivation of AChE was fo
und to be 0.197 mM. It was found that MPP(+) is neither a substrate of
AChE nor the time-dependent inactivator. The studies of reaction kine
tics indicate the inactivation of AChE to be a linear mixed-type inhib
ition. The inactivation of AChE by MPP(+) was partially recovered by e
ither dilution or gel exclusion chromatography. These data suggest tha
t once MPP(+) enters the basal ganglia of the brain, it can inactivate
the AChE and thereby increase the acetylcholine level in the basal ga
nglia,leading to potential cell dysfunction. It appears likely that th
e nigrostriatal toxicity by MPP(+) leading to Parkinson's disease-like
syndrome may, in part, be mediated via the AChE inactivation.