Model study on the bioreduction of paraquat, MPP+, and analogs. Evidence against a "redox cycling" mechanism in MPTP neurotoxicity.
The ability of paraquat, MPP+, and analogs to be reduced by chemical reductants and by NADPH, as catalyzed by liver microsomes or purified NADPH cytochrome P-450 reductase, is reported. The analogs span a range of electrochemical potential, including values in-between that of paraquat and MPP+. Analogs with an Eo below -.55 V (vs. NHE) are not reduced by either the NADPH-microsomes or NADPH-reductase systems. The inability of MPP+ to be bio-reduced or to stimulate the production of superoxide during aerobic reduction is evidence against a redox-cycling (oxidant stress) role of MPP+ in MPTP neurotoxicity.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010269:Paraquat / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism* / Q000633:toxicity; D011726:Pyridinium Compounds / Q000378:metabolism* / Q000633:toxicity; D013329:Structure-Activity Relationship
D011725:Pyridines; D011726:Pyridinium Compounds; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010269:Paraquat; D015655:1-Methyl-4-phenylpyridinium