Inhibition of mitochondrial alpha-ketoglutarate dehydrogenase by 1-methyl-4-phenylpyridinium ion.
Effects of 1-methyl-4-phenylpyridinium ion (MPP+) on the activities of NAD+- or NADP+-linked dehydrogenases in the TCA cycle were studied using mitochondria prepared from mouse brains. Activities of NAD+- and NADP+-linked isocitrate dehydrogenases, NADH- and NADPH-linked glutamate dehydrogenases, and malate dehydrogenase were little affected by 2 mM of MPP+. However, alpha-ketoglutarate dehydrogenase activity was significantly inhibited by MPP+. Kinetic analysis revealed a competitive type of inhibition. Inhibition of alpha-ketoglutarate dehydrogenase may be one of the important mechanisms of MPP+-induced inhibition of mitochondrial respiration, and of neuronal degeneration.
D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D001921:Brain / Q000378:metabolism; D002952:Citric Acid Cycle; D066298:In Vitro Techniques; D007655:Ketoglutarate Dehydrogenase Complex / Q000037:antagonists & inhibitors*; D007658:Ketone Oxidoreductases / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010101:Oxygen Consumption; D011726:Pyridinium Compounds / Q000494:pharmacology*
D011726:Pyridinium Compounds; D009243:NAD; D009249:NADP; D007658:Ketone Oxidoreductases; D007655:Ketoglutarate Dehydrogenase Complex; D015655:1-Methyl-4-phenylpyridinium