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Effects of Substitution of Methionine, Leucine, Phenylalanine, or Valine by Their -Hydroxy Analogs in the Diet of Rats¹

Department of Pharmacology and Experimental Therapeutics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Weanling male rats were fed diets containing essential amino acids as the sole source of nitrogen at a level of either 6 or 15% by weight of the diet. When L-valine was replaced isonitrogenously by calcium L--hydroxyisovalerate in the 15% amino acid diet, growth ceased and urea excretion increased; urea clearance was unaffected. When L-leucine was replaced isonitrogenously by calcium L--hydroxyisocaproate in this diet, growth and feed efficiency fell approximately 60% and urea excretion rose, but urea clearance doubled. L-Phenylalanine was replaced both isonitrogenously and without supplemental glutamate by calcium L-phenyllactate in both the 6 and 15% amino acid diets and was also added in twice equimolar quantities to the 6% amino acid diet. When the 15% amino acid diet was fed, growth was severely reduced, but when the 6% diet was fed, the double dose of phenyllactate reduced growth and feed efficiency only 25%. Urea clearance was not consistently altered. When D,L-methionine was replaced by calcium D,L--hydroxy--thiobutyrate in the 15% amino acid diet, growth and feed efficiency improved whether or not glutamate was added to make diets isonitrogenous, and also whether or not 0.1% neomycin was included. Urea clearance did not differ among these groups but was significantly higher in rats receiving the hydroxy analog or D,L-methionine than that in controls receiving L-methionine. Thus, the ability of these hydroxy analogs to replace the corresponding amino acids in the diet of rats varies from complete (methionine) to partial (leucine and phenylalanine) or virtually nonexistent (valine).

KEY WORDS: • -hydroxy acids • amino acids • growth • urea metabolism

¹ Supported by USPHS/NIH Research Grant AM 15603, Training Grant GM 01183 from the United States Public Health Service and by a grant-in-aid from Merck Sharp & Dohme, Inc.

Manuscript received 24 September 1974.

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