Characteristics of acetaldehyde oxidation in rat liver mitochondria.
Rat liver mitochondria oxidized acetaldehyde (180 muM) at the rate of approximately 12 nmol/min/mg of protein at 37 degrees. This was stimulated by 88% with the addition of ADP. The ADP/O ratio (2.6) was similar to that with glutamate as substrate. 2,4-Dinitrophenol and phenazine methosulfate also stimulated the rate of acetaldehyde oxidation in the mitochondria. By contrast, acetaldehyde metabolism was virtually abolished by rotenone and antimycin A. These results indicate that acetaldehyde oxidation is linked to the mitochondrial respiratory chain and coupled with mitochondrial oxidative phosphorylation. Indeed, little acetaldehyde was metabolized when mitochondrial membranes were disrupted by sodium deoxycholate. In the disrupted mitochondria, however, acetaldehyde oxidation was fully recovered by addition of NAD+, suggesting that the ability of mitochondria to supply NAD+ controls the rate of acetaldehyde oxidation in intact mitochondria. The stimulatory effect of ADP on mitochondrial acetaldehyde oxidation was diminished by increasing the acetaldehyde concentration. Concomitantly, the ADP/O ratio decreased, suggesting an inhibitory effect of high concentrations of acetaldehyde on mitochondrial respiration. Chronic feeding of ethanol significantly reduced the capacity of intact liver mitochondria to oxidize acetaldehyde. This was associated with a significant reduction of the mitochondrial respiration. By contrast, the activity of aldehyde dehydrogenase in disrupted mitochondria remained unchanged.
D000079:Acetaldehyde / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D002458:Cell Fractionation; D004140:Dinitrophenols / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D013386:Succinates / Q000378:metabolism
D004140:Dinitrophenols; D005971:Glutamates; D013386:Succinates; D012402:Rotenone; D000431:Ethanol; D000244:Adenosine Diphosphate; D000968:Antimycin A; D000445:Aldehyde Oxidoreductases; D005969:Glutamate Dehydrogenase; D000079:Acetaldehyde