New Developments in Glutamine Delivery

Abstract

Numerous studies demonstrate that free glutamine can be added to commercially available crystalline amino acid-based preparations before their administration. Instability during heat sterilization and prolonged storage and limited solubility (35 g/L at 20°C) hamper the use of free glutamine in the routine clinical setting. Indeed, there are many well-controlled and valuable trials with free glutamine, yet its use is restricted to clinical research. The obvious limitations of using free glutamine initiated an intensive search for alternative substrates. Synthetic glutamine dipeptides are stable under heat sterilization and highly soluble; these properties qualify the dipeptides as suitable constituents of nutritional preparations. Industrial production of these dipeptides at a reasonable price is an essential prerequisite for implications of dipeptide-containing solutions in clinical practice. Recent development of novel synthesis procedures allows increased capacity in industrial-scale production. Basic studies with synthetic glutamine-containing short-chain peptides provide convincing evidence that these new substrates are cleared rapidly from plasma after parenteral administration, without being accumulated in tissues and with negligible loss in urine. The presence of membrane-bound as well as tissue-free extracellular hydrolase activity facilitates a prompt and quantitative peptide hydrolysis, the liberated amino acids being available for protein synthesis and/or generation of energy. In the clinical setting, glutamine dipeptide nutrition beneficially influences outcome (nitrogen balance, immunity, gut integrity, hospital stay, morbidity and mortality). The provision of conditionally indispensable glutamine should be considered a necessary replacement of a deficiency rather than a supplementation. The beneficial effects observed with glutamine dipeptide nutrition should be seen simply as a correction of disadvantages produced by the inadequacy of conventional clinical nutrition. The availability of stable dipeptide preparations certainly facilitates, for the first time, adequate amino acid nutrition of critically ill, malnourished or stressed patients in the routine clinical setting and, thus, represents a new dimension in artificial nutrition.

Clostridium difficile Toxin A Induces Intestinal Epithelial Cell Apoptosis and Damage: Role of Gln and Ala-Gln in Toxin A Effects

“…These drawbacks can be overcome by the use of the stable and highly soluble dipeptide, alanyl-glutamine (Ala-Gln) (15). Thus, this study shows the effect of toxin A on important aspects of intestinal barrier integrity and repair, such as cell migration, apoptosis, necrosis, and transepithelial resistance, and demonstrates the protective activity of Gln and its stable derivative AlaGln on both physical injury and toxin A-induced damage (16).…”

Alanyl-Glutamine and Glutamine Supplementation Improves 5-Fluorouracil-Induced Intestinal Epithelium Damage In Vitro

“…Rat intestinal jejunal crypt cells (IEC-6, passages [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] were purchased from American Type Culture Collection (Rockville, MD) and were cultured at 37°C in a 5% CO 2 incubator. The maintenance cell media was Dulbecco's modified eagle media (DMEM; Gibco BRL, Grand Island, NY) supplemented with 5% fetal calf serum (FCS), 5 mg bovine insulin, 50 μg/ml penicillin/streptomycin (DMEM; Gibco BRL, Grand Island, NY), and a final concentration of 1 mM sodium pyruvate.…”

“…Glutamine supplementation in rats pretreated with toxic doses of methotrexate enables reduction in the severity of the intestinal mucositis [17] and improves intestinal permeability in patients treated with 5-FU and folinic acid [18]. Although glutamine has been shown to reduce diarrhea duration in children [19][20][21] and is generally recognized to be a conditionally essential amino acid in the critically ill patient [22], there remains a debate regarding the efficacy of glutamine due to its limited solubility, stimulating the pursuit of more stable glutamine compounds for clinical use [23,24].…”

Suplementação enteral e parenteral com glutamina em neonatos pré-termo e com baixo peso ao nascer

“…Este fato deve-se à limitada solubilidade da glutamina em água (35 g/L de água, a 20 o C) (Furst, 2001), bem como à possível neurotoxicidade decorrente dos produtos da decomposição desse aminoácido: ácido piroglutâmico e amônia (Furst, Albers, Stehle, 1990). Uma alternativa que possibilita a adição de glutamina a fórmulas parenterais consiste na utilização de dipeptídeos contendo glutamina, como o L-alanil-L-glutamina, que permanece estável durante a esterilização com calor e é altamente solúvel em água (568 g/L) (Furst, 2001). Todavia, há escassez de estudos envolvendo a suplementação com dipeptídeos contendo glutamina para neonatos PT e com BPN.…”