Multiple biochemical effects in the pathogenesis of alcoholic fatty liver

S Eaton, CO Record, K Bartlett - European journal of clinical …, 1997 - Wiley Online Library
S Eaton, CO Record, K Bartlett
European journal of clinical investigation, 1997Wiley Online Library
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 β‐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 …
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 β‐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.
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