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Effects of Dietary Protein Content and Glucoagon Administration on Tyrosine Metabolism and Tyrosine Toxicity in the Rat¹

Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706

Rats fed a low protein diet containing 3% or more of tyrosine develop external pathological lesions, accompanied by retardation of growth and decreased food intake. These adverse effects can be alleviated by increasing the protein content of the diet or by glucagon injection. Tissue tyrosine concentrations were much lower in rats consuming a 24% casein diet containing 5% of tyrosine than in rats consuming a 6% casein + 5% tyrosine diet. When rats ingesting a 6% casein + 5% tyrosine diet were injected with glucagon, their plasma tyrosine concentration was much below that of controls without hormonal treatment. Enzymatic studies showed that both tyrosine aminotransferase and p-hydroxyphenylpyruvate hydroxylase activities increased when dietary protein content was increased, whereas only tyrosine aminotransferase activity was induced by the high tyrosine diet. Administration of glucagon did not elevate tyrosine aminotransferase more than tyrosine alone and caused no apparent alteration in p-hydroxyphenylpyruvate hydroxylase activity. Homogentisate oxygenase activity was not affected by the protein content of the diet but seemed to be depressed by excess tyrosine. In order to assess how rats fed a 24% casein diet or injected with glucagon were able to handle the extra load of tyrosine more efficiently, effects of these treatments on the ability of the rat to oxidize tyrosine were measured using L-tyrosine-1-¹⁴C. Oxidation studies showed that rats that had been fed a 24% casein diet with or without tyrosine were able to metabolize more tyrosine than those fed a 6% casein diet. Similarly, rats that had been injected with glucagon had a greater capacity to metabolize tyrosine than controls without hormonal treatment. Moreover, in rats previously fed the higher protein diet, the response of tyrosine aminotransferase upon the administration of a loading dose of tyrosine was greater. The beneficial effect of the higher dietary protein content in alleviating tyrosine toxicity thus seems to be exerted at the enzymatic level, by providing the animal with a greater potential for removing an excessive amount of amino acid. These observations also illustrate that protein deficiency limits the ability of the rat to respond to an amino acid load.

KEY WORDS: • tyrosine toxicity • tyrosine catabolic enzymes • metabolism

¹ Supported by funds from the College of Agriculture and Life Sciences, University of Wisconsin-Madison, Madison, Wisc., and by Public Health Service Grant AM 10747 from the National Institute of Arthritis and Metabolic Diseases.

Manuscript received 4 June 1973.