Role of diacetyl metabolite in alcohol toxicity and addiction via electron transfer and oxidative stress
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- Kovacic, P. & Cooksy, A.L. Arch Toxicol (2005) 79: 123. doi:10.1007/s00204-004-0602-z
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There are many gaps in our knowledge of the molecular basis of alcohol toxicity and addiction. Metabolism affords mainly acetic acid via acetaldehyde. A minor metabolite, diacetyl (an α-dicarbonyl), arises from the aldehyde. We propose that this C4 entity and/or its iminium derivatives from condensation with protein amino groups plays important roles in bioresponses. A review of the literature reveals substantial support for this premise. Reduction potentials for diacetyl and its iminium derivatives fall in the range favorable for catalytic electron transfer in vivo, which can generate oxidative stress via reactive oxygen species due to redox cycling. Oxidative stress and reactive oxygen species are linked to toxicity associated with major organs by alcohol. The α-dicarbonyl moiety in related substances is believed to induce various toxic responses, such as Alzheimer’s disease, mutagenesis, and carcinogenesis. In addition to discussion of addiction and computational studies, potential applications for health improvement are suggested.