Metabolism of lysosomal enzymes in the protein-deficient weanling rat

We have shown that the protein-deficient weanling rat fed a 3% casein diet, within 2 to 4 wk, exhibits marked changes in serum lysosomal hydrolases similar to those observed in children suffering from protein-calorie malnutrition: serum hexosaminidase, alpha-mannosidase, and beta-glucuronidase activities increase 3-fold, 2-fold, and 50%, respectively, whereas the acid phosphatase levels decrease by 50%. Rehabilitation of the protein-deficient animals with a diet containing 25% protein (i.e., casein) results in a rapid restoration of the plasma lysosomal hydrolase profiles to normal in less than 1 wk. The specific activities of various tissue lysosomal enzymes change significantly in the protein-deficient animals; however, no overall consistent pattern of change is apparent. In general, the greatest number of changes in lysosomal enzymes occurs in the kidney, whereas the brain exhibits the smallest differences between experimental and control animals in this regard. Perfusion experiments have shown that the rate of release of lysosomal enzymes from livers of rats fed the protein-deficient diet is profoundly altered when compared to that of control animals. Studies of the variation of enzyme secretion with time have demonstrated that the rate of secretion of hexosaminidase by the liver remains low and then rises markedly (3-fold) after the animals have been consuming the 3% casein diet for 16 days. In contrast, the secretion of both acid phosphatase and beta-glucuronidase is markedly depressed in the early phase of protein malnutrition (i.e., 7 to 16 days), and then increases greatly by the 3rd wk. These results demonstrate that changes occur in the rate of secretion of lysosomal enzymes by the liver during the course of experimental protein malnutrition.