Degradation of Acetaldehyde Produced by the Nonalcohol Dehydrogenase Pathway

Abstract

Acetaldehyde (Ac-CHO) is produced via the oxidation of ethanol by two different pathways; alcohol dehydrogenase (ADH) and non-ADH systems. However, degradation of Ac-CHO in the liver, especially with respect to the relative amounts produced by the two pathways, remains unclear. In order to clarify the metabolic fates of Ac-CHO produced by the two pathways, the ethanol metabolic rate (EMR) and hepatic Ac-CHO levels in the rats fed an alcohol-containing or control diet for 4 weeks were determined after a single administration or constant infusion of ethanol, with or without 4-methylpyrazole pretreatment. The EMR was increased in chronic alcoholic rats and decreased by treatment with 4-methylpyrazole. Consequently, blood and hepatic Ac-CHO levels were low in the pyrazole-treated rats in both the single dose and infusion experiments. Hepatic Ac-CHO levels and EMR were well correlated in both experiments. However, the correlations were curve linear and the slopes of the regression lines in the pyrazole-treated rats were steeper than those in the nontreated rats. When the ratios of hepatic Ac-CHO (subtracted by a constant which was obtained from the correlation equations for the curvilinear fit of hepatic Ac-CHO levels and EMR) to EMR were calculated, they were significantly higher in the pyrazole-treated rats than in the nontreated rats of the perfusion experiment, without relation to chronic alcohol ingestion. These results suggest that Ac-CHO produced by the non-ADH pathway degrades more slowly than that produced by the ADH pathway in the liver.