Molecular alterations in the respiratory chain of rat liver after chronic ethanol consumption.

Mitochondria, submitochondrial particles, and hepatocytes prepared from the livers of rats treated chronically with ethanol (36% calories, 40 days) exhibited significant alterations in the content of specific respiratory chain components. As measured by heme absorbance, the amounts of substrate-reducible cytochromes aa3 and b were each decreased about 50%, while the amount of cytochromes c plus c1 was unchanged after chronic ethanol treatment. The amounts of extractable flavin and ubiquinone associated with the respiratory chain were also unaltered. The effects of an altered cytochrome ratio on electron transport were studied by measurements of the aerobic reduction levels of the cytochromes during steady state respiration using submitochondrial particles. The aerobic reduction patterns observed after chronic ethanol treatment reflected the differential alterations in amounts of respiratory chain components present in the membranes, as well as the intrinsic kinetic characteristics of respiratory. The most notable change was observed during ascorbate oxidation, in which case cytochrome c was maintained at a higher level of steady state reduction. The results suggest that at the level of the electron transport chain itself, the lower respiratory rates found after chronic ethanol treatment arise, at least in part, from specific alterations in the content of particular electron transfer chain carriers, but that different alterations limit the rate of respiration with different substrates.