Digestive Activity of Lysosomes

Abstract

The hydrolysis of acid-denatured human or bovine globin at 37" by extracts of highly purified rat liver lysosomes was most extensive between pH 4.4 and 5.6.After exhaustive digestion under these conditions, the ninhydrin-positive material released by enzymatic hydrolysis amounted to 70% of that released by acid hydrolysis.The main products of hydrolysis were free amino acids (42% of the total amino acid residues of the protein) and small peptides, mostly dipeptides.Ammonia, and probably asparagine and glutamine, was also present in the enzymatic hydrolysate.The peptides that were resistant to the lysosomal enzymes were found to be partly degraded when incubated at pH 8.0 with a high speed supernatant from rat liver.Acid-denatured bovine serum albumin was also attacked by the lysosomal enzymes, although less efficiently than globin.Similar tests performed with undenatured globin, serum albumin, peroxidase, invertase, and ferritin indicated that the susceptibility of these proteins to lysosomal digestion depended on their sensitivity to denaturation under the incubation conditions.Furthermore, the relative stability of the proteins in the system in vitro paralleled their reported ability to persist intact within liver lysosomes in viva This suggests that the information provided by the present experiments may be directly relevant to the physiological process of protein degradation within lysosomes.Considerable evidence has accumulated in recent years indicating that lysosomes play an important role in the intracellular digestion of materials taken in by endocytosis or segregated