MULTIPLE BIOCHEMICAL EFFECTS IN THE PATHOGENESIS OF ALCOHOLIC FATTY LIVER

The pathogenesis of alcoholic fatty liver is unknown, but several caus es have been proposed based on biochemical findings. These include the metabolism of alcohol leading to a shift in the cytosolic [NAD(+)]/[N ADH] ratio to reduction, which in turn causes a direct inhibition of b eta-oxidation and enhanced triacylglycerol formation via the [glycerol -3-phosphate]/[dihydroxyacetone phosphate] ratio. There are also chron ic effects of ethanol on hepatic enzyme activities. Thus, increased ac tivity of phosphatidate phosphohydrolase, an increased amount of fatty acid binding protein, decreased secretion of very low-density lipopro tein 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 n utritional and genetic factors would then lead to the heterogeneity of the severity and characteristics of the steatosis observed in human a lcoholics.