EFFECT OF TOTAL PARENTERAL-NUTRITION ON AMINO-ACID AND GLUCOSE-TRANSPORT BY THE HUMAN SMALL-INTESTINE

Objective The effect of total parenteral nutrition (TPN) on small intestinal amino acid transport activity was studied in humans. Summary Background Data Studies in humans receiving TPN indicate that a decrease in the activities of the dissacharidase enzymes occurs, but morphologic changes are minimal with only a slight decrease in villous height. Methods Surgical patients were randomized to receive TPN (n = 6) or a regular oral diet (controls, n = 7) for 1 week before abdominal surgery. Ileum (5 controls, 5 TPN) or jejunum (2 controls, 1 TPN) were obtained intraoperatively and brush-border membrane vesicles (BBMV) were prepared by magnesium aggregation/differential centrifugation. Transport of L-MeAlB (a selective system A substrate), L-glutamine, L-alanine, L-arginine, L-leucine, and D-glucose was assayed by a rapid mixing/filtration technique in the presence and absence of sodium. Results Vesicles demonstrated approximately 18-fold enrichments of enzyme markers, classic overshoots, transport into an osmotically active space, and similar 1-hour equilibrium values, TPN resulted in a 26-44% decrease in the carrier-mediated transport velocity of all substrates except glutamine across ileal BBMVs. In the one patient receiving TPN from whom jejunum was obtained, there was also a generalized decrease in nutrient transport, although glutamine was least affected. Kinetic studies of the system A transporter demonstrated that the decrease in uptake was secondary to a reduction in carrier V(max), consistent with a decrease in the number of functional carriers in the brush-border membrane. Conclusions TPN results in a decrease in brush-border amino acid and glucose transport activity. The observation that glutamine transport is not downregulated by 1 week of bowel rest may further emphasize the important metabolic role that glutamine plays as a gut fuel and in the body's response to catabolic stresses.