Effects of chronic ethanol consumption on the respiratory chain of rat liver submitochondrial particles

Studies of hepatic submitochondrial particles, which provide an experimental system allowing direct measurements of electron transfer independent of substrate transport reactions, showed that chronic ethanol ingestion (36% calories, 40 days) lowered the specific respiratory rates associated with substrate oxidation. NADH oxidase activity was decreased about 40%, succinoxidase was decreased 25%, and oxidation in ascorbate mediated by phenazine methosulfate was decreased 20%. The content of dithionite-reducible cytochrome aa3 was decreased 38%, while that of cytochrome b was decreased 8%, and that of cytochromes c + c1 was decreased 14%. Steady state kinetic measurements indicated that the turnover number of cytochrome oxidase was unchanged, about 15 s-1 under uncoupled conditions with NADH as substrate. When electron flux to cytochrome c was maximal, cytochrome c was maintained in a more highly reduced state relative to cytochrome aa3 in submitochondrial particles from the ethanol-treated rat compared to those from the control rat. This finding is consistent with the greater decrease in cytochrome aa3 content relative to that of cytochrome c. The results indicate that the diminished content of cytochrome oxidase is one of the factors responsible for the lower respiration rates caused by chronic ethanol consumption.