Abstract
The intestinal barrier integrity is essential for the absorption of nutrients and health in humans and animals. Dysfunction of the mucosal barrier is associated with increased gut permeability and development of multiple gastrointestinal diseases. Recent studies highlighted a critical role for glutamine, which had been traditionally considered as a nutritionally non-essential amino acid, in activating the mammalian target of rapamycin cell signaling in enterocytes. In addition, glutamine has been reported to enhance intestinal and whole-body growth, to promote enterocyte proliferation and survival, and to regulate intestinal barrier function in injury, infection, weaning stress, and other catabolic conditions. Mechanistically, these effects were mediated by maintaining the intracellular redox status and regulating expression of genes associated with various signaling pathways. Furthermore, glutamine stimulates growth of the small intestinal mucosa in young animals and also enhances ion transport by the gut in neonates and adults. Growing evidence supports the notion that glutamine is a nutritionally essential amino acid for neonates and a conditionally essential amino acid for adults. Thus, as a functional amino acid with multiple key physiological roles, glutamine holds great promise in protecting the gut from atrophy and injury under various stress conditions in mammals and other animals.
Abbreviations
- ASCT2:
-
Neutral amino acid transporter type 2
- ATP:
-
Adenosine triphosphate
- BSO:
-
Buthionine sulfoximine
- DP:
-
Dipeptidase
- EAA:
-
Essential amino acids
- 4EBP1:
-
Eukaryotic translation initiation factor 4E-binding protein-1
- eIF4E:
-
Eukaryotic translation initiation factor 4E
- FOXO:
-
Forkhead box O transcription factor
- GA:
-
GlutaminaseGALT gut-associated lymphatic tissue
- GCL:
-
Glutamate cysteine ligase
- GS:
-
Glutamine synthetase
- GSH:
-
Glutathione
- GSS:
-
Glutathione synthetase
- GSSG:
-
Glutathione disulfide
- γ-GT:
-
γ-Glutamyl transpeptidase
- Ig:
-
Immunoglobulin
- IκB:
-
Inhibitor of NF-κB
- α-KG:
-
α-Ketoglutarate
- IUGR:
-
Intrauterine growth restriction
- MAPK:
-
Mitogen-activated protein kinases
- MS:
-
Methionine sulfoximine
- mTOR:
-
Mammalian target of rapamycin
- mTORC:
-
mTOR complex
- NADH:
-
Reduced form of nicotinamide adenine dinucleotide
- NADPH:
-
Reduced form of nicotinamide adenine dinucleotide phosphate
- NF-κB:
-
Nuclear factor-κB
- NO:
-
Nitric oxide
- NOS:
-
NO synthase
- p70S6k:
-
p70 Ribosomal protein S6 kinase
- PI3K:
-
Phosphatidylinositol 3-kinase
- PKB/AKT:
-
Protein kinase B
- PPP:
-
Pentose phosphate pathway
- Rheb:
-
Ras homologue enriched in brain
- ROS:
-
Reactive oxygen species
- RTK:
-
Receptor tyrosine kinase
- SNAT2:
-
Sodium coupled neutral amino acid transporter 2
- TCL:
-
Tricarboxylic acid cycle
- TNF-α:
-
Tumor necrosis factor-alpha
- TPN:
-
Total parenteral nutrition
- Trx:
-
Reduced thioredoxin
- TrxSS:
-
Oxidized thioredoxin
- TSC:
-
Tuberous sclerosis complex
- ZO-1:
-
Zonula occludens protein 1
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Acknowledgments
This work was supported by National Key Basic Research Program (2013CB127302), the Natural Science Foundation of China (31172217, 31272450, 31301979, and 31272451), the Chinese Universities Scientific Fund (2013RC002), the Program for New Century Excellent Talents in University (NCET-12-0522), and the Program for Beijing Municipal Excellent Talents, and Texas A&M AgriLife Research (H-8200).
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Wang, B., Wu, G., Zhou, Z. et al. Glutamine and intestinal barrier function. Amino Acids 47, 2143–2154 (2015). https://doi.org/10.1007/s00726-014-1773-4
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DOI: https://doi.org/10.1007/s00726-014-1773-4