Decreases in hepatocyte NAD+ produced by ethanol are only partially explained by the increased conversion of NAD+ to NADH and NADP+. The purpose of this study was to determine whether a mechanism for the ethanol-induced decrease in NAD+ is its increased use in ADP-ribosylation. Exposure of hepatocyt
Ethanol increases the formation of NADP+ in rat hepatocytes
β Scribed by B. Emmanuel Akinshola; James J. Potter; Esteban Mezey
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- English
- Weight
- 646 KB
- Volume
- 13
- Category
- Article
- ISSN
- 0270-9139
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β¦ Synopsis
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 high-performance 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 mumol 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.
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