Role of peroxisomes in the swift increase in alcohol metabolism.
The Swift Increase in Alcohol Metabolism occurs within 2.5 h after an acute gavage of ethanol causing an increase in hepatic respiration, an increase in alcohol metabolism, and pericentral hypoxia in the perfused liver. Alcohol treatment causes a release of endotoxin, activation of Kupffer cells to produce PGE(2), therefore, stimulating mitochondrial function resulting in an increase in cofactor supply for nicotinamide adenine dinucleotide (NAD)-dependent alcohol metabolism and depletion of glycogen reserves. Additionally, liberation of peripheral fatty acids via activation of an adrenergic response to alcohol provides added substrate for peroxisomes. In this study, rats were treated in vivo with ethanol, methanol or oleate and basal rates of oxygen uptake in perfused liver were significantly increased as compared to untreated controls. Methanol (25 mmol/L), a selective substrate for catalase in rodents, was infused into the liver and rates of methanol metabolism were increased 3-4-fold as compared to controls. Gadolinium chloride blocked the increase in oxygen and alcohol metabolism and inhibited the increase in ketogenesis normally observed after ethanol treatment. Excess fatty acids from oleate treatment in vivo provided additional substrate for peroxisomal alcohol metabolism and an increase in alcohol metabolism occurred even when Kupffer cells were eliminated. These data demonstrate that fatty acid supply either via peripheral reserves or after fatty acid treatment to peroxisomes generate sufficient H(2)O(2) for activation of catalase-dependent alcohol metabolism.
Bradford
Blair U
BU
Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. blair_bradford@unc.edu
D000818:Animals; D002374:Catalase / Q000502:physiology; D000431:Ethanol / Q000378:metabolism* / Q000493:pharmacokinetics*; D008658:Inactivation, Metabolic / Q000502:physiology*; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000502:physiology*; D020675:Peroxisomes / Q000378:metabolism*; D051381:Rats
D000431:Ethanol; D002374:Catalase