The effects of combinations of acetaldehyde, ethyl alcohol and an oxybarbiturate on the rate of oxygen consumption, the ADP/O ratio and energy-dependent swelling by rat liver mitochondria have been investigated. The effects of similar combinations on the rate of oxygen uptake by submitochondrial preparations, oxidizing several different substrates, have also been studied. Acetaldehyde at millimolar levels increased the rate of oxygen consumption by rat liver mitochondria which had been preincubated with ADP, inhibited NAD+-linked oxidations by mitochondrial and submitochondrial preparations, and increased the rate of the energy-dependent swelling of rat liver mitochondria with suceinate as substrate. Combinations of acetaldehyde, ethyl alcohol and an oxybarbiturate interacted to reduce the rate of oxygen consumption by rat liver mitochondria and the energy-dependent swelling of rat liver mitochondria when dl-3-hydroxybutyrate was the substrate. Ethyl alcohol was not involved in these interactions. The effects of all combinations tested could be ascribed to interactions) between acetaldehyde and an oxybarbiturate or to activities of acetaldehyde or the oxybarbiturate only. In the case of state 3 respiration and uncoupled mitochondrial respiration, acetaldehyde and the tested oxybarbiturates behaved as additive inhibitors. All of the results are consistent with the view that the NADH-ubiquinone segment (Complex 1) of the mitochondrial electron transport chain is the site of an acetaldehyde-oxybarbiturate interaction to inhibit electron transport.
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