Acrolein inhibits NADH-linked mitochondrial enzyme activity: Implications for Alzheimer's disease

Chava B. Pocernich, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


In Alzheimer's disease (AD) brain increased lipid peroxidation and decreased energy utilization are found. Mitochondria membranes contain a significant amount of arachidonic and linoleic acids, precursors of lipid peroxidation products, 4-hydroxynonenal (HNE) and 2-propen-1-al (acrolein), that are extremely reactive. Both alkenals are increased in AD brain. In this study, we examined the effects of nanomolar levels of acrolein on the activities pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH), both reduced nicotinamide adenine dinucleotide (NADH)-linked mitochondrial enzymes. Acrolein decreased PDH and KGDH activities significantly in a dose-dependent manner. Using high performance liquid chromatography coupled to mass spectrometry (HPLCMS), acrolein was found to bind lipoic acid, a component in both the PDH and KGDH complexes, most likely explaining the loss of enzyme activity. Acrolein also interacted with oxidized nicotinamide adenine dinucleotide (NAD+) in such a way as to decrease the production of NADH. Acrolein, which is increased in AD brain, may be partially responsible for the dysfunction of mitochondria and loss of energy found in AD brain by inhibition of PDH and KGDH activities, potentially contributing to the neurodegeneration in this disorder.

Original languageEnglish
Pages (from-to)515-519
Number of pages5
JournalNeurotoxicity Research
Issue number7
StatePublished - 2003

Bibliographical note

Funding Information:
Kentucky Department of Chemistry and Director of the Mass Spectrometry Center for his assistance in obtaining the ESI-MS data of this study. This work was supported in part by grants from NIH [AG-10836; AG-05119].


  • Acrolein
  • Lipoic acid
  • Mitochondria
  • Pyruvate dehydrogenase
  • α-Ketoglutarate dehydrogenase

ASJC Scopus subject areas

  • General Neuroscience
  • Toxicology


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