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Proline and hydroxyproline metabolism: implications for animal and human nutrition

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Abstract

Proline plays important roles in protein synthesis and structure, metabolism (particularly the synthesis of arginine, polyamines, and glutamate via pyrroline-5-carboxylate), and nutrition, as well as wound healing, antioxidative reactions, and immune responses. On a per-gram basis, proline plus hydroxyproline are most abundant in collagen and milk proteins, and requirements of proline for whole-body protein synthesis are the greatest among all amino acids. Therefore, physiological needs for proline are particularly high during the life cycle. While most mammals (including humans and pigs) can synthesize proline from arginine and glutamine/glutamate, rates of endogenous synthesis are inadequate for neonates, birds, and fish. Thus, work with young pigs (a widely used animal model for studying infant nutrition) has shown that supplementing 0.0, 0.35, 0.7, 1.05, 1.4, and 2.1% proline to a proline-free chemically defined diet containing 0.48% arginine and 2% glutamate dose dependently improved daily growth rate and feed efficiency while reducing concentrations of urea in plasma. Additionally, maximal growth performance of chickens depended on at least 0.8% proline in the diet. Likewise, dietary supplementation with 0.07, 0.14, and 0.28% hydroxyproline (a metabolite of proline) to a plant protein-based diet enhanced weight gains of salmon. Based on its regulatory roles in cellular biochemistry, proline can be considered as a functional amino acid for mammalian, avian, and aquatic species. Further research is warranted to develop effective strategies of dietary supplementation with proline or hydroxyproline to benefit health, growth, and development of animals and humans.

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Abbreviations

AA:

Amino acid

IUGR:

Intrauterine growth retardation

mTOR:

Mammalian target of rapamycin

NRC:

National Research Council

P5C:

Pyrroline-5-carboxylate

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Acknowledgments

This work was supported, in part, by grants from National Institutes of Health (1R21 HD049449), National Research Initiative Competitive Grants (2008-35206-18764, 2008-35203-19120, and 2009-35206-05211) from the USDA Cooperative State Research, Education, Texas AgriLife Research (H-8200), North Carolina Agricultural Experiment Station, and the Thousand-People-Talent program at China Agricultural University. We thank graduate students, postdoctoral fellows, technicians, and many collaborators for their important contributions to the work described in this article.

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Wu, G., Bazer, F.W., Burghardt, R.C. et al. Proline and hydroxyproline metabolism: implications for animal and human nutrition. Amino Acids 40, 1053–1063 (2011). https://doi.org/10.1007/s00726-010-0715-z

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