DIETARY MODULATION OF AMINO-ACID-TRANSPORT IN RAT AND HUMAN LIVER

Specialized diets enriched in the amino acids glutamine and arginine h ave been shown to benefit surgical patients. In the liver, glutamine s upports glutathione biosynthesis, arginine regulates nitric oxide synt hesis, and both of these amino acids serve as precursors for ureagenes is, gluconeogenesis, and acute phase protein synthesis. The effects of a diet enriched with glutamine and arginine on hepatic plasma membran e transport activity have not been studied in humans. We hypothesized that feeding supradietary amounts of these nutrients would enhance the activities of the specific carriers which mediate their transmembrane transport in the liver. We fed surgical patients (n = 8) and rats (n = 6) one of three diets: a) a regular diet, b) an enteral liquid diet containing arginine and glutamine, or c) an enteral diet supplemented with pharmacologic amounts of glutamine and arginine. Diets were isoca loric and were administered for 3 days. Hepatic plasma membrane vesicl es were prepared from rat liver and from human wedge biopsies obtained at laparotomy. The transport of glutamine and arginine by rat and hum an vesicles was assayed. Vesicle integrity and functionality were veri fied by osmolarity plots, enzyme marker enrichments, and time courses. Provision of both a standard enteral liquid diet and one enriched wit h glutamine and arginine increased the activities of Systems N (glutam ine) and y(+) (arginine) in rat and human liver compared to a control diet. The diet supplemented with glutamine and arginine was the most e ffective in increasing transport activity. We conclude that the liver responds to diets enriched with specific amino acids by increasing mem brane transport activity, This adaptive response provides essential pr ecursors for hepatocytes which may enhance hepatic synthetic functions during catabolic states. This study provides insights into the mechan isms by which enteral nutrition regulates nutrient transport at the ce llular level and may provide a biochemical rationale for the use of fo rmulas which are enriched with conditionally essential nutrients. (C) 1996 Academic Press, Inc.