Protein metabolism in alcoholism: Effects on specific tissues and the whole body

Ethanol is one of the few nutrients that is profoundly toxic. Alcohol cause s both whole-body and tissue-specific changes in protein metabolism. Chroni c ethanol misuse increases nitrogen excretion with concomitant loss of lean tissue mass. Even acute doses of alcohol elicit increased nitrogen excreti on. The loss of skeletal muscle protein (i.e., chronic alcoholic myopathy) is one of several adverse reactions to alcohol and occurs in up to two-thir ds of all ethanol misusers. There are a variety of other diseases and tissu e abnormalities that are entirely due to ethanol-induced changes in the amo unts of individual proteins or groups of tissue proteins; for example, incr eased hepatic collagen in cirrhosis, reduction in myosin in cardiomyopathy, and loss of skeletal collagen in osteoporosis. Ethanol induces changes in protein metabolism in probably all organ or tissue systems. Clinical studie s in alcoholic patients without overt liver disease show reduced rates of s keletal muscle protein synthesis though whole-body protein turnover does no t appear to be significantly affected. Protein turnover studies in alcohol misusers are, however, subject to artifactual misinterpretations due to non -abstinence, dual substance misuse (e.g., cocaine or tobacco), specific nut ritional deficiencies, or the presence of overt organ dysfunction. As a con sequence, the most reliable data examining the effects of alcohol on protei n metabolism is derived from animal studies, where nutritional elements of the dosing regimen can be strictly controlled. These studies indicate that, both chronically and acutely, alcohol causes reductions in skeletal muscle protein synthesis, as well as of skin, bone, and the small intestine. Chro nically, animal studies also show increased urinary nitrogen excretion and loss of skeletal muscle protein. With respect to skeletal muscle, the reduc tions in protein synthesis do not appear to be due to the generation of rea ctive oxygen species, are not prevented with nitric oxide synthase inhibito rs, and may be indirectly mediated by the reactive metabolite acetaldehyde. Changes in skeletal muscle protein metabolism have profound implications f or whole body physiology, while protein turnover changes in organs such as the heart (exemplified by complex alterations in protein profiles) have imp ortant implications for cardiovascular function and morbidity. (C) Elsevier Science Inc.