Ethanol increases the formation of NADP⁺ in rat hepatocytes

The acute effects of ethanol on total (bound + free) pyridine dinucleotides were determined in freshly isolated rat hepatocytes. Pyridine dinucleotides and adenine nucleotides were determined by highperformance liquid chromatography. Exposure of the hepatocytes to 8 mmol/L ethanol resulted in a decrease in NAD⁺ and an increase in NADP⁺ after 2 min incubation. There were no significant changes in NADH and NADPH. Ethanol decreased ATP and increased AMP after 2 min, whereas an increase in ADP was only apparent after 15 min of incubation. Ethanol 8 mmol/L and 100 mmol/L resulted in an increased incorporation of [³²P] into NADP⁺ from [³²P]‐prelabeled NAD⁺ and ATP. Ethanol increased hepatocyte NAD⁺ kinase activity; this effect was blocked by 4‐methylpyrazole but reproduced by 10 μmol acetaldehyde. These observations indicate that ethanol increases the synthesis of NADP⁺ and that this effect is most likely the result of increased NAD⁺ kinase activity. The ethanol‐induced decrease of NAD⁺ may limit ADP ribosylation of nuclear proteins, whereas increases in NADP⁺ may stimulate the pentose phosphate cycle. (HEPATOLOGY 1991;13:509–14.)