Antagonism of arginine by excess dietary lysine in the growing dog.

Experiments were conducted with growing English Pointer puppies to examine the effects of ingesting excess lysine. A purified crystalline amino acid basal diet containing 0.40% L-arginine (the arginine requirement for maximal weight gain) and 0.91% L-lysine was fed in all assays. All diets were kept isonitrogenous by the addition of diammonium citrate, and lysine was supplied as L-lysine acetate. Both weight gain and gain/feed were reduced in the presence of 4% excess dietary lysine. However, 1 and 2% excess supplemental lysine had no effect on performance. In a second experiment, a growth response to supplemental arginine was obtained in the presence, but not in the absence, of a growth-depressing level of lysine (4%). Therefore, lysine appeared to depress growth by antagonizing arginine. The mechanism of the lysine-arginine antagonism was examined in a third experiment. Classic signs of arginine deficiency: orotic aciduria, depressed urea formation, hyperammonemia, a reduction in weight gain, and emesis were observed in puppies consuming excess lysine but not in their pair-fed controls. Excess lysine ingestion neither inhibited nor induced liver arginase, but it did result in a generalized amino aciduria early in the experiment. In addition, lysine did not appear to affect arginine absorption. Therefore, the mechanism behind the lysine-arginine antagonism in the dog remains to be elucidated.