Alcohol, liver injury and protein metabolism

Two mechanisms play a major role in mediating the effects of ethanol on intermediary metabolism which includes protein metabolism and liver injury. Ethanol is oxidized in the liver to 2 products (hydrogen and acetaldehyde) to which many of the effects of ethanol can be attributed. The hydrogen generation alters the redox state, and although this effect is attenuated after chronic ethanol consumption, it still may be sufficient to explain alterations in lipid and carbohydrate metabolism, possibly increased collagen deposition, and, under special circumstances, depression of the synthesis of protein whereas secretion of proteins is affected by acetaldehyde. It is noteworthy that after chronic consumption of ethanol, acetaldehyde is increased, in part, because of its decreased oxidation in the mitochondria, and, partly because of induction of an alternate pathway of ethanol metabolism, namely the microsomal ethanol oxidizing system. Increased acetaldehyde is associated with impaired function of microtubles, protein retention and swelling of the hepatocyte. Acetaldehyde also exerts toxicity with regards to other key cellular sites; it interferes with oxidations in the mitochondria, and it may promote peroxidation of cellular membranes. Hepatocellular injury is followed by extracellular collagen deposition, but what eventually attracts an increased number of myofibroblasts and promotes fibrosis is not known. Alcoholic hepatitis, when present, can obviously trigger fibrosis, but the cirrhotic process occurs even in the absence of florid alcoholic hepatitis. Cirrhosis can develop despite an associated adequate diet. However, decreased intake of dietary protein or decreased absorption of amino acids derived from dietary protein may contribute to the depletion of amino acids in the liver which, in turn, may potentiate the toxicity of alcohol. Selective deficiencies, such as those of methionine or vitamin A, may also play a contributory role.