Orotic aciduria caused by feeding excess lysine to growing rats

Two 14-day factorial experiments were performed to assess changes in growth, feed intake and urinary orotic acid excretion of weanling male Sprague-Dawley rats. The dietary variables investigated included the percentage of dietary casein in the basal diet, its supplementation with 5% lysine-HCl or 1% arginine-HCl and sucrose or two parts dextrin and one part sucrose as the only form of carbohydrate. The response to 5% supplemental lysine was strikingly similar to that seen with arginine-free diets. With 5% lysine added to 15% casein diets, growth decreased 25% and feed efficiency 20% while orotic acid excretion increased significantly. When 5% lysine was added to diets with 7.5 or 30% casein, these responses were smaller and were prevented by the simultaneous feeding of 1% arginine. Growth depression by lysine was partially reversed by replacing two-thirds of the dietary sucrose with dextrin. When unsupplemented, the casein diets containing only sucrose as carbohydrate supported less growth than the same diets containing the dextrin sucrose mixture. This difference was abolished by supplementation with 1% arginine, suggesting that sucrose increases arginine requirements for optimal growth. The data are consistent with the conclusion that orotic acid excretion is a useful index for determining when lysine excess is producing a functional deficiency of arginine.