Review: How Amino Acids Get Into Cells: Mechanisms, Models, Menus, and Mediators

Souba, Wiley W.; Pacitti, Anthony J.

doi:10.1177/0148607192016006569

Cited by 109 publications

(45 citation statements)

References 24 publications

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“…In addition to the maintenance of glutamine transport during hypoxia, glutamine perfusion increases glutamine transport regardless of oxygenation status. This observation is consistent with those of other nutrient transporters, wherein the provision of the nutrient specific to the transporter will increase that transporter's maximal transport rate (27). These data illustrate a differential regulation of both glucose and glutamine transporters during hypoxia.…”

Section: Discussionsupporting

confidence: 85%

Hypoxia differentially regulates nutrient transport in rat jejunum regardless of luminal nutrient present

Kles¹,

Tappenden

2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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nutrition and poor intestinal perfusion are hypothesized to play an important pathogenic role in nonocclusive small bowel necrosis. This study tests the hypothesis that glucose and glutamine transport are differentially regulated during hypoxia regardless of the luminal nutrient present. Sprague-Dawley rats (247 Ϯ 3 g; n ϭ 16) were randomized to receive 1 h of intestinal hypoxia or serve as normoxic controls. During this hour, jejunal loops were randomized to receive in situ perfusions of mannitol, glucose, or glutamine. When compared with normoxic groups, glucose but not glutamine transport was impaired (P Ͻ 0.001) during hypoxia. Messenger RNA abundance of the sodium glucose cotransporter sodium-dependent glucose cotransporter-1 (SGLT-1) and neutral basic amino acid transporter B o did not differ with hypoxia or nutrient perfused. Jejunal brush-border SGLT-1 abundance was decreased (P ϭ 0.039) with hypoxia; however, total cellular SGLT-1 protein abundance did not differ among treatment groups. These data indicate that SGLT-1 activity is regulated during hypoxia at the posttranslational level. Additional information regarding the mechanisms regulating nutrient transport in the hypoperfused intestine is critical for optimizing the composition of enteral nutrient formulas.sodium-dependent glucose cotransporter-1; nutrient absorption; small intestine THE INCIDENCE OF NONOCCLUSIVE small bowel necrosis is significant in traumatically injured patients, despite adequate systemic resuscitation. Currently, the causative mechanism remains unknown; however, enteral nutrition has been provided in ϳ90% of cases (21), suggesting that the inappropriate administration of specific nutrients into a poorly perfused small bowel may play a pathogenic role (12,21,23,25). During states of low blood flow to the intestine, enteral nutrients may increase oxygen demand beyond that available, potentially increasing intestinal hypoxia and impairing intestinal function. Gastrointestinal function has been shown to be impaired during hypoperfusion or decreased oxygenation of the intestine (28). Previous in vivo rat studies from our lab indicate that, during hypoperfusion, impaired barrier function, increased lactate concentration, decreased ATP concentration, and altered nutrient transport are characteristic (15). The detrimental effects of hypoperfusion may be minimized with an enteral formula composed of nutrients easily processed by the hypoperfused intestine.The purpose of the current study was to determine how nutrient perfusion alters sodium-dependent glucose and glutamine transport activity and their regulation at the cellular level during hypoperfusion. Glutamine transport occurs via system B o , which is part of a family of transporters for neutral amino acids (14). Glucose transport occurs via the sodium-glucose cotransporter [sodium-dependent glucose cotransporter-1 (SGLT-1)]. We previously reported that, during hypoxia, brush-border glucose transport is impaired, but glutamine transport remains unaltered following luminal perfusio...

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Section: Discussionsupporting

confidence: 85%

Hypoxia differentially regulates nutrient transport in rat jejunum regardless of luminal nutrient present

Kles¹,

Tappenden

2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The uptake buffer components were adjusted so that the final concentration mixture contained initial gradients of 120 mM NaCl or KCI and labeled substrate at 10-to 50-,uM concentrations. The reaction was initiated by rapidly vibrating the tube, and, after the prescribed reaction period (15 seconds-I hour), 1 …”

Section: Transport Measurementsmentioning

confidence: 99%

Growth Hormone Enhances Amino Acid Uptake by the Human Small Intestine

1994

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ObjectiveThe effects of growth hormone (GH) on the luminal transport of amino acids and glucose by the human small intestine were investigated. Summary Background DataThe anabolic effect of growth hormone administration is associated with nitrogen retention and an increase muscle strength, but the impact of growth hormone on nutrient uptake from the gut lumen has not been examined. MethodsTwelve healthy patients received a daily subcutaneous dose of low-dose GH (0.1 mg/kg), highdose GH (0.2 mg/kg), or no treatment (controls) for 3 days before surgery. At operation, ileum (8 patients) or jejunum (4 patients) was resected, and brush border membrane vesicles (BBMVs) were prepared by differential centrifugation. Vesicle purity was confirmed by a 16-fold enrichment of marker enzymes. The carrier-mediated transport of glutamine (System B), leucine (System L), alanine (System B), arginine (System y+), MeAIB (methyl a-aminoisobutyric acid [System A]), and glucose (Na+-dependent glucose transporter) by BBMVs was measured by a rapid mixing/ filtration technique. ResultsTreatment with low-dose GH resulted in a statistically insignificant increase in amino acid transport rates in jejunal and ileal BBMVs. High-dose GH resulted in a generalized 20%-to 70%-stimulation of amino acid transport, whereas glucose transport was not affected. The effects of GH were similar in ileum and jejunum. Kinetic analysis of the transport of glutamine (the most abundant amino acid in the body and the principal gut fuel) and the essential amino acid leucine revealed that the increase in transport was caused by a 50% increase in carrier Vmax, consistent with an increase in the number of functional carriers in the brush border membrane. Pooled analysis of transport velocities demonstrated that total rates of amino acid uptake from the gut lumen were increased significantly by 35% in GH-treated patients. ConclusionsThe ability of GH to enhance amino acid uptake from the gut lumen provides energy and precursors for protein synthesis in the gut mucosa, as well as additional substrate for anabolism in other organs. 715

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“…Intestinal absorption of only one essential amino acid was studied and not the entire cascade of digestion and absorption following a protein-containing meal. The transport of amino acids into the cytoplasm and through the basolateral membrane is facilitated by highly regulated transporter systems defined on the kinetic properties of the specific amino acid (20,21). Transport of amino acids such as leucine in the intestinal brush border is regulated by the L and B 0.8 system (21,22) and is predominantly Na ϩ -dependent (22).…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy Does Not Influence Intestinal Amino Acid Uptake in Children

et al. 2007

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Chemotherapy will frequently induce intestinal damage (mucositis). Enteral nutrition is then often withheld for fear of impaired intestinal absorption as shown in animal models. There is no clinical evidence, however, that absorption is indeed compromised during chemotherapy-induced mucositis. The aim of this study was to evaluate systemic availability of dietary amino acids (leucine) during chemotherapy-induced mucositis. We studied eight childhood cancer patients (age 1.5-16 y) on 2 d, i.e. the day before chemotherapy and 3-5 d after. Chemotherapy-induced oral mucositis and diarrhea were scored on a World Health Organization toxicity scale. Stable isotope tracers were used to measure first-pass splanchnic leucine uptake and whole-body leucine kinetics. Patients showed increased mucositis and/or diarrhea toxicity scores (p Ͻ 0.0001) after chemotherapy. Systemic availability of enterally administered leucine was not significantly affected by chemotherapy (before 60%, after 90%, p ϭ 0.46). Interestingly, five patients already showed a negative leucine balance before chemotherapy. In conclusion, most children receiving chemotherapy are already catabolic before start of a new cycle of chemotherapy. Amino acid transport as measured by leucine uptake in the intestine is not affected by chemotherapyinduced mucositis. C hemotherapy may severely damage the intestinal mucosa, resulting in a condition referred to as mucositis (1,2). Mucositis is characterized by major morphologic changes of the intestinal epithelium, such as epithelial flattening, villus atrophy, and specific down-regulation of the enterocytespecific gene expression that is crucial for degradation and absorption of nutrients (3-5). It is unknown how this condition effects digestion and absorption of enteral nutrition.Normally, the intestine itself metabolizes a substantial part of the nutrients absorbed from the intestinal lumen in first-pass splanchnic uptake (6,7). Animal and human studies have shown that 20 -80% of dietary essential amino acids are used within the intestine (8 -10). The more nutrients are used by the small intestine, the fewer essential amino acids are systemically available for whole-body energy metabolism and protein synthesis. It is unknown whether chemotherapy-induced mucositis affects first-pass splanchnic amino acid uptake. We hypothesized, first, that chemotherapy-induced mucositis will lead to lower nutrient uptake by the intestine and, second, that it will lead to a higher intestinal utilization rate due to mucosal regeneration. The combined result would be a lower systemic availability of dietary amino acids.To test these hypotheses we determined first-pass splanchnic uptake of dietary leucine, an essential amino acid, in pediatric patients before and after receiving mucotoxic chemotherapy. METHODS Subjects.The ethics review board of the Erasmus MC-Sophia Children's Hospital approved the study. Informed consent was obtained from parents and patients, as appropriate. Eligible subjects were patients aged between 1 and...

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Review: How Amino Acids Get Into Cells: Mechanisms, Models, Menus, and Mediators

Cited by 109 publications

References 24 publications

Hypoxia differentially regulates nutrient transport in rat jejunum regardless of luminal nutrient present

Hypoxia differentially regulates nutrient transport in rat jejunum regardless of luminal nutrient present

Growth Hormone Enhances Amino Acid Uptake by the Human Small Intestine

Chemotherapy Does Not Influence Intestinal Amino Acid Uptake in Children

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