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 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.
Akinshola
B E
BE
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Potter
J J
JJ
Mezey
E
E
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D009243:NAD; D000431:Ethanol; D009249:NADP