Parenteral glycyl-L-tyrosine maintains tyrosine pools and supports growth and nitrogen balance in phenylalanine-deficient rats

Poor solubility hampers the addition of sufficient amounts of free tyrosine to parenteral amino acid solutions. We investigated the use of a highly soluble synthetic dipeptide, glycyl-L-tyrosine, as a parenteral tyrosine source in 18 male Wistar rats (body weight 180-200 g). The animals were randomized into three equal groups and catheterized to facilitate isoenergetic (1.2 MJ . kg(-1). d(-1)) and isonitrogenous (1.25 g nitrogen . kg(-1). d(-1)) total parenteral nutrition for 7 d. Controls (Group 1) received a complete amino acid solution, Group 2 received the same solution deficient in phenylalanine (nitrogen replaced with glycine), and group 3 received the phenylalanine-deficient solution supplemented with glycyl-L-tyrosine. Between d 4 and 7, weight gain and nitrogen retention were lower in Group 2 than in Group 1 or 3. In plasma and organ samples obtained at the end of the study, amino acids and dipeptides were analyzed by means of reversed phase-HPLC. In Group 2, phenylalanine and tyrosine concentrations were lower than in controls in plasma, muscle and kidney; in liver, only the tyrosine concentration was lower compared with controls. With glycyl-tyrosine supplementation, plasma, liver and kidney tyrosine concentrations and the phenylalanine:tyrosine ratio were normal. Intact glycyl-L-tyrosine was not detectable, suggesting a virtually quantitative elimination or utilization of the infused dipeptide. The results indicate that in phenylalanine-deficient rats, parenteral glycyl-L-tyrosine rapidly provides free tyrosine to facilitate normal growth, promote nitrogen metabolism and maintain intra- and extracellular tyrosine pools.