Luminal amino acids acutely decrease intestinal mucosal protein synthesis and protease mRNA in piglets

Because parenteral feeding is associated with negative N balance and reduce d rates of protein synthesis in intestinal mucosa, we hypothesized that lum inal exposure to specific amino acids or energy fuels would stimulate intes tinal protein synthesis. We studied the acute effects of luminal nutrients on mucosal protein synthesis in the absence of systemic influences. Multipl e jejunal segments constructed in piglets deprived of food overnight (n = 6 ) were randomly assigned to luminal perfusion with saline, 30 mmol/L amino acid mixture with or without 50 mmol/L glucose, or 30 mmol/L glutamine for 90 min. Protein synthesis was then measured by luminal perfusion with L-[2, 6-H-3]-phenylalanine. Energy substrates (glucose, short-chain fatty acids o r beta-hydroxybutyrate) had no effect on mucosal protein synthesis. Relativ e to saline, a 30 mmol/L amino acid mixture or 30 mmol/L glutamine suppress ed mucosal protein synthesis by 20-25% (P < 0.05), On the basis of these su rprising results, we speculated that a coordinate reduction of proteolytic processes would be required to maintain positive intestinal N balance. Alth ough intestinal protein catabolism cannot be assessed directly, the 30 mmol /L amino acid mixture acutely suppressed mucosal levels of mRNA encoding ub iquitin, 14-kDa ubiquitin conjugating enzyme and the C9 subunit of the prot easome by 20-30% (P < 0.05), demonstrating the sensitivity of components of the ATP-ubiquitin proteolytic pathway to acute regulation by nutrients, Th e suppression of protein synthesis by luminal amino acids in the absorptive state might lower intestinal utilization of amino acids to ensure efficien t allocation of absorbed nutrients to nonintestinal tissues.