Multiple biochemical effects in the pathogenesis of alcoholic fatty liver.
The pathogenesis of alcoholic fatty liver is unknown, but several causes have been proposed based on biochemical findings. These include the metabolism of alcohol leading to a shift in the cytosolic [NAD+]/ [NADH] ratio to reduction, which in turn causes a direct inhibition of beta-oxidation and enhanced triacylglycerol formation via the [glycerol-3-phosphate]/[dihydroxyacetone phosphate] ratio. There are also chronic effects of ethanol on hepatic enzyme activities. Thus, increased activity of phosphatidate phosphohydrolase, an increased amount of fatty acid binding protein, decreased secretion of very low-density lipoprotein and impairment of the respiratory chain as a result of decreased protein synthesis or decreased amounts of ubiquinone could all lead to fat accumulation and steatosis. The interplay of each of these with nutritional and genetic factors would then lead to the heterogeneity of the severity and characteristics of the steatosis observed in human alcoholics.
Eaton
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S
Department of Medicine, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
Record
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Bartlett
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D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000096:biosynthesis
D005227:Fatty Acids; D008055:Lipids; D014280:Triglycerides; D009243:NAD; D000431:Ethanol