Inhibition of mitochondrial alpha-ketoglutarate dehydrogenase by 1-methyl-4-phenylpyridinium ion

Biochem Biophys Res Commun. 1987 Mar 30;143(3):971-6. doi: 10.1016/0006-291x(87)90346-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium
  • Animals
  • Brain / metabolism
  • Citric Acid Cycle
  • In Vitro Techniques
  • Ketoglutarate Dehydrogenase Complex / antagonists & inhibitors*
  • Ketone Oxidoreductases / antagonists & inhibitors*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism*
  • NAD / metabolism
  • NADP / metabolism
  • Oxygen Consumption
  • Pyridinium Compounds / pharmacology*


  • Pyridinium Compounds
  • NAD
  • NADP
  • Ketone Oxidoreductases
  • Ketoglutarate Dehydrogenase Complex
  • 1-Methyl-4-phenylpyridinium