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Glutamine, arginine, and leucine signaling in the intestine

Abstract

Glutamine and leucine are abundant constituents of plant and animal proteins, whereas the content of arginine in foods and physiological fluids varies greatly. Besides their role in protein synthesis, these three amino acids individually activate signaling pathway to promote protein synthesis and possibly inhibit autophagy-mediated protein degradation in intestinal epithelial cells. In addition, glutamine and arginine stimulate the mitogen-activated protein kinase and mammalian target of rapamycin (mTOR)/p70 (s6) kinase pathways, respectively, to enhance mucosal cell migration and restitution. Moreover, through the nitric oxide-dependent cGMP signaling cascade, arginine regulates multiple physiological events in the intestine that are beneficial for cell homeostasis and survival. Available evidence from both in vitro and in vivo animal studies shows that glutamine and arginine promote cell proliferation and exert differential cytoprotective effects in response to nutrient deprivation, oxidative injury, stress, and immunological challenge. Additionally, when nitric oxide is available, leucine increases the migration of intestinal cells. Therefore, through cellular signaling mechanisms, arginine, glutamine, and leucine play crucial roles in intestinal growth, integrity, and function.

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Abbreviations

ARG:

l-Arginine

ERK:

Extracellular signal-related kinase

GLN:

l-Glutamine

HO:

Heme oxygenase

hsp:

Heat shock proteins

LEU:

l-Leucine

MAPK:

Mitogen-activated protein kinase

MEK:

MAPK kinase

mTOR:

Mammalian target of rapamycin

NO:

Nitric oxide

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Acknowledgments

This work was supported, in part, by grants from National Institutes of Health (1RO3-DK57774) and USDA (NRCGIP 02092) (JMR), the Ochsner Clinic Foundation (JMR), The University of Texas Medical School at Houston (JMR), National Research Initiative Competitive Grants (2008-35206-18764, and 2008-35203-19120) from the USDA Cooperative State Research, Education, and Extension Service (GW), and Texas AgriLife Research (H-8200) (GW). The authors thank Drs. Teresa A. Davis and Nick E. Flynn for helpful comments on this paper.

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Correspondence to J. Marc Rhoads.

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Marc Rhoads, J., Wu, G. Glutamine, arginine, and leucine signaling in the intestine. Amino Acids 37, 111–122 (2009). https://doi.org/10.1007/s00726-008-0225-4

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Keywords

  • Amino acids
  • Cellular signaling
  • Intestine
  • Nutrition