Regulation of protein turnover by l-glutamine in porcine intestinal epithelial cells

Enteral delivery of proteins stimulates protein synthesis in human duodenal mucosa in the fed state through a mammalian target of rapamycin–independent pathway

“…To better understand the underlying mechanisms involved in the effects of protein delivery, we studied intracellular phosphokinases as previously described (19,34). We did not observe the activation of the mTOR pathway that usually mediates the effects of amino acids on protein translation in muscle (35) and intestinal cells (12,16,20,36). Neither mTOR nor downstream components such as the p70S6kinase or factor 4E binding protein 1 were affected by the protein supply.…”

“…Glutamine, which is the preferential substrate of rapidly dividing cells (ie, enterocytes and immune cells), is associated with less-infectious complications in critically ill patients (10) that could be partly due to the maintenance of gut barrier function (11). In vitro data showed that glutamine increased protein synthesis in intestinal epithelial cells (12)(13)(14)(15)(16). In animals, glutamine enhanced intestinal protein synthesis in hypercatabolic dogs (17) but not in malnourished rats (18).…”

“…One major pathway involved in the regulation of the initiation and elongation of protein synthesis by amino acids is the mammalian target of rapamycin (mTOR) 4 pathway. In intestinal epithelial cells, recent in vitro studies showed that glutamine enhanced protein synthesis through an activation of the mTOR pathway (12,16), but data in the human gut are lacking. We reported that enteral leucine infusion failed to activate the mTOR pathway in human duodenal mucosa (19), whereas leucine activated mTOR pathway in intestinal epithelial cells in vitro (20)(21)(22) or in animals (23,24).…”

Functional amino acids in nutrition and health

“…Based on the foregoing lines of compelling evidence from animal and human studies, Wu (2010) proposed the new concept of functional AA, which are defined as those AA that participate in and regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of the organisms. Metabolic pathways include: (1) intracellular protein turnover (synthesis and degradation) and associated events (Bertrand et al 2012;Kong et al 2012;Wauson et al 2013;Xi et al 2011Xi et al , 2012Yao et al 2012), (2) AA synthesis and catabolism (Brosnan and Brosnan 2012;Lei et al 2012a, b), (3) generation of small peptides, nitrogenous metabolites, and sulfur-containing substances [e.g., H 2 S (Mimoun et al 2012)], (4) urea cycle and uric acid synthesis (Wu 2013), (5) lipid and glucose metabolism Go et al 2012;Satterfield et al 2011Satterfield et al , 2012, (6) one-carbon unit metabolism (Wang et al 2012), and (7) cellular redox signaling (Hou et al 2012a). Functional AA can be nutritionally ''essential'', ''nonessential'', or conditionally essential AA (Table 1).…”

Glutamine metabolism in advanced age

“…59,60 Glutamine is a key regulator of amino acidcontrolled cell growth through the mammalian target of rapamycin (mTOR) signaling pathway in rat intestinal epithelial cells. 27,28,31,39,42,61,62 Amino acids are important signaling regulators, especially for p70 S6 kinase and eIF-4E binding protein 1 via mTOR, which have 2 structurally and functionally distinct complexes termed mTORC1 and mTORC2. mTORC1 is activated by nutrients (amino acids), growth factors, and cellular energy, while mTORC2 is activated by growth factors alone.…”