ARS | Publication request: Comparative Aspects of Tissue Glutamine and Proline Metabolism

Submitted to: Journal of Nutrition
Publication Type: Review Article
Publication Acceptance Date: August 1, 2008
Publication Date: October 1, 2008
Citation: Bertolo, R.F., Burrin, D.G. 2008. Comparative aspects of tissue glutamine and proline metabolism. Journal of Nutrition. 138:2032S-2039S.

Technical Abstract: The cellular metabolism of glutamine and proline are closely interrelated since they can be interconverted with glutamate and ornithine via the mitochondrial pathway involving pyrolline-5-carboxylate (P5C). In adults, glutamine and proline are converted via P5C to citrulline in the gut, then citrulline is converted to arginine in the kidney. In neonates, arginine is a semi-indispensable amino acid and is synthesized from proline completely in the gut; because of low P5C synthase activity, glutamine is not an important precursor for neonatal arginine synthesis. Thus, splanchnic metabolism of glutamine and proline is important as both amino acids serve as key precursors for arginine synthesis with some developmental differences. Studies investigating splanchnic extraction demonstrate that about two-thirds of dietary glutamine and almost all dietary glutamate are extracted on first pass and the vast majority is oxidized in the gut. This capacity to extract glutamine and glutamate appears to be very large, so diets high in glutamine or glutamate probably have little impact on circulating concentrations and consequent potential toxicity. In contrast, it appears that very little proline is extracted by the gut and liver, at least in the neonate, which may result in hyperprolinemia and potential toxicity. Therefore, the upper limits of safe dietary intake for glutamine and proline, and other amino acids, appear to be substantially different depending on the extent of first pass splanchnic extraction and irreversible catabolism.