The swift increase in alcohol metabolism. Time course for the increase in hepatic oxygen uptake and the involvement of glycolysis.

Gastric intubation of female Sprague-Dawley rats with 5 g of ethanol/kg body wt. nearly doubled oxygen uptake by the isolated perfused rat liver maximally after only 2.5 h of treatment (Swift Increase in Alcohol Metabolism). Inhibition of enhanced oxygen uptake by KCN (2mM) and 4-methylpyrazole (0.8 mM) suggested the involvement of the mitochondrial respiratory chain and alcohol dehydrogenase in this phenomenon. Glycolysis was depressed after ethanol treatment. Diminished ATP generation via glycolysis accounts for a portion (23-50%) of the increased oxygen uptake, assuming that other rates of biosynthesis remain constant. Injection of adrenaline (2 mg/kg) 1 h before perfusion mimicked partially the action of ethanol on hepatic oxygen uptake. The increases produced by ethanol and adrenaline were not additive, suggesting that adrenaline is involved in the action of ethanol. Moreover, the increase in hepatic oxygen uptake produced by 2.5 h of ethanol treatment could be blocked by either alpha-(phenoxybenzamine; 40 mg/kg) or beta-(propranolol; 40 mg/kg) adrenergic blocking agents. Blood glucose increased after ethanol treatment, supporting the involvement of glycogenolytic hormones in this effect. These data indicate that at least part of the stimulated oxygen uptake after treatment with ethanol is a result of lower rates of glycolytic ATP generation resulting from hormone (e.g. adrenaline etc.) action. The ADP not phosphorylated in the cytosol enters the mitochondria, where it stimulates oxygen uptake.