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Parenteral Glycyl-L-Tyrosine Maintains Tyrosine Pools and Supports Growth and Nitrogen Balance in Phenylalanine-Deficient Rats^1,2,

Institute for Biological Chemistry and Nutrition, University of Hohenheim, D-70593 Stuttgart, Germany

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-L-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.

KEY WORDS: • rats • tyrosine • dipeptide • parenteral nutrition • in vivo utilization

¹ Supported in part by grants from Fresenius AG (Bad Homburg, Germany), the Bundesminister für Forschung und Technologie (BMFT no. 031900B) and Degussa AG (Hanau, Germany).

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ Current address: Institute for Nutrition, University of Bonn, D-53115 Bonn, Germany.

⁴ Current address: BASF AG, MEV/AC-D 205, D-67056 Ludwigshafen, Germany.

⁵ To whom correspondence should be addressed.

Manuscript received 5 May 1996. Revision accepted 11 November 1995.

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