Role of acetaldehyde in ethanol-induced increase in the activity of phosphatidate phosphatase in rat liver.
The effect of ethanol on the activity of phosphatidate phosphatase was studied in rat liver using membrane-bound phosphatidate and phosphatidate emulsion as substrate. A single large dose of ethanol (5 g/kg body wt) caused an increase in the enzyme activity measured with membrane-bound phosphatidate after an approximate 2-hr lag period in both cytosolic and microsomal fraction and the increase was approximately 2.2- and 1.8-fold that in control rats at 5 hr in cytosol and microsomes, respectively. A similar time-course of the increase was obtained with phosphatidate emulsion as substrate. These ethanol-induced increases in the activity of cytosolic and microsomal phosphatidate phosphatase were blocked by the pretreatment of rats with actinomycin D. The ethanol-induced rise in the activity of cytosolic and microsomal phosphatidate phosphatase measured with membrane-bound phosphatidate was abolished when rats were injected with pyrazole prior to ethanol administration. On the other hand, pretreatment with cyanamide enhanced the increase in cytosolic activity produced by a suboptimal dose of ethanol (1 g/kg), while microsomal activity was not affected by the same treatment, suggesting that acetaldehyde may be selectively involved in the ethanol-induced increase in the activity of cytosolic phosphatidate phosphatase. This hypothesis was supported by a finding that administration of paraldehyde, a cyclic trimer of acetaldehyde, produced an increase (35%) in cytosolic activity, but not in microsomal activity.
D000079:Acetaldehyde / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D003484:Cyanamide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D010242:Paraldehyde / Q000494:pharmacology; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011720:Pyrazoles; D003609:Dactinomycin; D000431:Ethanol; C031280:pyrazole; D003484:Cyanamide; D010744:Phosphoric Monoester Hydrolases; D010711:Phosphatidate Phosphatase; D000079:Acetaldehyde; D010242:Paraldehyde