Clinical Nutrition (1995) 14:105-115 © Pearson Professional Ltd 1995 Effect of an enterally administered glutamine-rich protein on the catabolic response to a zymosan challenge in rats O. E. ROOYACKERS, P. B. SOETERS*, W. H. M. SARIS and A. J. M. WAGENMAKERS Departments of Human Biology and *Surgery, University of Limburg, Maastricht, The Netherlands (Correspondence to OER, Endocrinology Research Division, Mayo Clinic, 200 1st Street SVV,Rochester MN 55905, USA) ABSTRACT-- Glutamine is considered to be a conditionally essential amino acid during critical illness and has, therefore, been advocated to be included in nutritional support supplied in these situations. We investigated whether a diet containing a protein source rich in glutamine can restore depleted glutamine pools (plasma and muscle) and counteract muscle wasting, in a rat model of critical illness (intraperitoneal injection of zymosan). A glutamine-rich protein source was obtained by mixing a wheat protein hydrolysate (25% glutamine) with a whey protein isolate (to prevent essential amino acid deficiency). Feeding healthy control rats for 2 weeks with an adequate diet containing this protein source increased the two main glutamine pools (plasma and muscle). However, no effect was observed on the following zymosan-induced changes: 1) decreased glutamine and arginine concentrations (plasma and muscle), 2) wasting of muscle protein, and 3) decreased mitochondrial content in skeletal muscle. We conclude that a diet containing a glutamine-rich protein source can be used to increase plasma and muscle glutamine concentrations in healthy rats, but is of limited value to counteract wasting of skeletal muscle in zymosan-treated rats. Introduction Glutamine has many regulatory functions in interme- diary metabolism. It is a carrier of nitrogen between cells, and a preferred respiratory fuel and precursor for nucleic acids and nucleotides for rapidly prolif- erating cells, e.g. lymphocytes and enterocytes (1). Skeletal muscle is the main source of glutamine production and also contains the largest intracellular glutamine pool. During disease and especially critical illness the muscle glutamine content decreases. Petersson and colleagues (2) observed a decreased ghitamine concentration in muscle up to 30 days following elective surgery. Wasting of muscle mass which is another characteristic feature of severe illness may additionally decrease the capacity of skeletal muscle to produce sufficient glutamine. Due to its key functions in metabolism and the decreased content in muscle, glutamine is considered to be conditionally essential (3). Supplying patients with extra glutamine, therefore, seems a desirable strategy. Critically ill patients often receive total parenteral nutrition (TPN) or enteral elemental diets. Normally no glutamine is present in these formulae because of its instability in solution. Also the limited solubility of glutamine makes it difficult to supply enough ghitamine as free amino acid. Therefore, alternative products such as glutamine containing dipeptides have been investigated extensively (4-9). Due to the high costs of these dipeptides usage in the clinic will be limited. We, therefore, investigated the effect of an adequate diet containing a hydrolysate of wheat protein, which is rich in glutamine, on the course of illness (measured as dally food intake and body weight) and the wasting of skeletal muscle in a rat model of critical illness. Wheat protein contains more glutamine than any other protein. Gene sequencing indicated that ap- proximately 35% of the amino acid residues are glutamine (3). To obtain a soluble protein source, rich in ghitamine, a wheat protein hydrolysate was used. This hydrolysate was mixed with whey protein to prevent essential amino acid deficiency. The first experiment was designed to elucidate whether healthy control rats would consume the diet and whether this would lead to increased concentrations of glutamine 105