Theoretical studies on mechanism of MPTP action: ET interference by MPP+ (1-methyl-4-phenylpyridinium) with mitochondrial respiration vs. oxidative stress.
This report demonstrates that ease of electron uptake by 1-methyl-4-phenylpyridinium (MPP+), apparently the active agent derived from MPTP, is influenced by conformation of the phenyl ring. From quantum mechanical calculations on MPP+, electron affinity is most negative for the nearly coplanar arrangement, indicating that the molecule is most readily reduced in this geometry. Ionization potential is largest in the perpendicular conformation, thus making for most facile oxidation in that form. Site binding would be expected to alter conformation in comparison with the situation in solution, and, hence, to influence reduction potential. We suggest that electron transfer by MPP+ may play a role in inhibition of mitochondrial respiration and in oxidative stress.
Kovacic
P
P
Department of Chemistry, University of Wisconsin-Milwaukee 53201.
Edwards
W D
WD
Ming
G
G
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism*; D015655:1-Methyl-4-phenylpyridinium / Q000737:chemistry / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004563:Electrochemistry; D004579:Electron Transport; D008928:Mitochondria / Q000378:metabolism*; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010101:Oxygen Consumption
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium