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Propargylglycine Infusion Effects on Tissue Glutathione Levels, Plasma Amino Acid Concentrations and Tissue Morphology in Parenterally-Fed Growing Rats^{1 ,2}

El Soon Cho³, Jane Hovanec-Brown, Robert J. Tomanek^* and Lewis D. Stegink

Department of Home Economics ^* Department of Anatomy Departments of Pediatrics and Biochemistry, The University of Iowa, Iowa City, IA 52242

Amino acid solutions currently used for total parenteral nutrition (TPN) contain little cysteine or cystine. Some premature human infants have low liver activities of -cystathionase and presumably require preformed cysteine or cystine. Growing animals tend to have higher liver -cystathionase activity, which makes them unsuitable as models to study effects of CSH precursors. Because propargylglycine (PPG) inhibits -cystathionase specifically, rats infused with PPG as part of a TPN regimen were evaluated as a potential model. Two groups of rats (120–160 g) were infused for 15 d with TPN regimens, one without and one with PPG (40 µmol/d). A third group received the TPN-control regimen, with methionine added at toxic levels. Propargylglycine treatment significantly decreased plasma cystine and taurine concentrations and significantly increased plasma cystathionine concentration without affecting methionine concentration. Propargylglycine treatment significantly decreased brain, muscle, liver, intestine and stomach glutathione concentration without affecting erythrocyte or heart glutathione concentrations. Electron microscopic examination showed no abnormalities in heart and kidney of PPG-treated rats. Hepatocyte glycogen was lower in TPN-fed controls than in orally fed rats and was further reduced in TPN-PPG-fed animals. Growing rats infused with low doses of PPG show promise as an animal model to study a number of important issues concerning human sulfur amino acid metabolism.

KEY WORDS: • cysteine • cystine • parenteral • rats • propargylglycine

¹ Supported by a grant-in-aid from the Nutrition Foundation.

² These data were presented in preliminary form at the 1982 meeting of the American Institute of Nutrition [Cho, E. S., Hovanec-Brown, J., Tomanek, R. & Stegink, L. D. (1982) Effect of propargylglycine (PG) on tissue morphology, tissue glutathione (GSH) levels, and plasma amino acid levels in parenterally (TPN)-fed growing rats. Fed. Proc. 41: 540 (abs. 1579)].

³ Present address: 404 Food Science Building, Food and Nutrition, Texas Tech University, Lubbock, TX 79409.

Manuscript received 25 July 1990. Revision accepted 24 October 1990.