ACETALDEHYDE METABOLISM BY LIVER MITOCHONDRIAL ALDH FROM UCHA AND UCHB RATS - EFFECT OF INHIBITORS

We have observed that blood acetaldehyde (AcH) levels after an ethanol dose were significantly higher in disulfiram-pre-treated UChA (low et hanol consumer) than in UChB (high ethanol consumer) rats. In order to explore these results further, we studied the effect of disulfiram (3 00 mg/kg i.p.) and chlorpropamide (80) mg/kg i.p.) pre-treatment on bl ood AcH levels after oral ethanol (60 mmol/kg) and on AcH metabolism b y fiver mitochondrial aldehyde(s) dehydrogenase(s) from UChA and UChB rats. AcH metabolism by liver mitochondrial aldehyde dehydrogenase (AL DH) was studied by following AcH disappearance rate and the formation of NADH at 340 nm in the incubation medium. The results showed that ch lorpropamide, like disulfiram, produced a higher blood AcH level consi stent with a greater inhibition of the low-Km mitochondrial ALDH in th e UChA rats than in the UChB rats. These drugs did not inhibit the hig h Km mitochondrial ALDH. Kinetic studies of mitochondrial ALDH show th at low-Km mitochondrial ALDH from UChB rats exhibits a higher affinity for NAD than UChA rats. This observation could explain the different inhibition of ALDH by both drugs, assuming that the inhibitors reduce NAD availability, the rate limiting step in the mitochondrial ALDH oxi dation.