Abstract

To assess the in vivo role of the microsomal ethanol oxidizing system (MEOS) , an improved assay procedure was developed. When corrected for losses of microsomes during the preparation, the activity of MEOS in vitro corresponded to 20 to 25% of the in vivo rate of ethanol metabolism in the rat and could account for most of the residual ethanol metabolism after inhibition of alcohol dehydrogenase by pyrazole. Under these conditions, the apparent K_m of MEOS in vitro coincided with the apparent K_m of the blood ethanol disappearance in vivo. Furthermore, administration of ethanol to rats for 24 days increased blood ethanol clearance, with a parallel rise in MEOS activity, whereas the activities of alcohol dehydrogenase and catalase remained unchanged or decreased. Moreover, barbiturate treatment for four to five days also increased total MEOS activity in the liver and this was accompanied by a moderate acceleration of blood ethanol clearance. The latter effect was masked however if significant amounts of barbiturates were still present in the blood when ethanol was given. In addition. administration of one dose of barbiturate slowed blood ethanol clearance and abolished its increase induced by ethanol pretreatment, suggesting that barbiturates interfere with the metabolism of ethanol. In view of the parallel increase of blood ethanol clearance in vivo and MEOS activity in vitro after ethanol or barbiturate pretreatment, it is proposed that MEOS plays a significant role in vivo, a conclusion supported by the correspondence of the kinetic data of MEOS in vitro and of blood ethanol clearance after alcohol dehydrogenase inhibition in vivo.