The adaptive increase in ethanol metabolism due to pretreatment with ethanol: a rapid phenomenon.

Simple models were developed to study changes in oxygen uptake in perfused rat liver and increases in ethanol metabolism in vivo. Results obtained 2.5 hours following a large dose of ethanol were quantitatively similar to those seen after 24 hours or 5 weeks. The rapidity of the increase indicated that SIAM represents an activation rather than an adaptation. Pathways responsible for the swift increase in alcohol metabolism (SIAM) in the perfused rat liver were investigated through the use of ouabain and were found to be related to diminished glycolysis and another unidentified pathway. Investigation of pathways responsible for the increase in ethanol metabolism in vivo following ethanol treatment implicated the alcohol dehydrogenase pathway as that mainly responsible for the adaptive increase, although a catalase-H2O2-dependent component was also involved. The rate of NADH reoxidation generally appeared to be the rate-limiting step. In addition, the genetic aspect of SIAM was indicated through selective breeding resulting in F1 generations of non-SIAM and SIAM rats.