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Effects of amino acid infusions on cell metabolism in hemodialyzed patients with uremia.

Eighteen uremic patients received i.v. infusions of a mixture of amino acids three times per week for 3 months in an effort to improve cellular amino acid imbalance and related cell bioactivities. They were a subset of 42 uremic patients stabilized by maintenance hemodialysis and were characterized by reduced cellular levels of threonine, isoleucine, methionine, and ornithine, with increased levels of aspartate, glycine, arginine, tyrosine, and phenylalanine. Protein synthesis (3H-leucine incorporation), energy level [energy charge = (ATP + 1/2 ADP)-(ATP + ADP + AMP)], and activity of the rate-limiting glycolytic enzyme pyruvate kinase were reduced in these patients compared with 32 control normal subjects. The circulating leukocyte (88 +/- 5% granulocytes) was used as a cell model. Previously, multiple regression best-subset analysis showed that a combination of the cell levels of aspartate, valine, isoleucine, ornithine, lysine, and tryptophan could "explain" 40% of the variance in protein synthesis in these patients. Similarly, a combination of the levels of aspartate, glutamic acid, glycine, ornithine, and arginine were "predictive" of the level of energy charge. We hypothesized that protein synthesis and energy level would be improved if the amino acid infusions normalized the intracellular levels of those amino acids that were predictive of the bioactivities. After 3 months of amino acid infusions, levels of the predictive intracellular amino acids were not improved, but deviated further from baseline values. Failure to detect significant improvement in the cell bioactivities is attributed to inability to correct the imbalance in the intracellular amino acid pool.