17.21 : Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane, counting discharged materials.

Lysosomal storage Diseases

Genetic defects in lysosomal function cause lysosomal storage diseases. In these diseases, the absence of lysosomal hydrolases results in undigested molecules accumulating in the lysosome. Organs containing such defective lysosomes malfunction, which can even lead to death. More than 40 of such diseases are known, affecting one in every 8000 infants. The symptoms of lysosomal storage diseases can range from very severe to barely detectable, depending on the degree of enzyme dysfunction. For example, Taysachs, the best-studied lysosomal storage disease, occurs due to the deficiency of an enzyme degrading ganglioside called N-hexosaminidase. In Hurler’s disease, the enzyme involved in glycosaminoglycan chain breakdown is either defective or missing. Undigested glycogen accumulates in lysosomes in the absence of enzyme glucosidase. This causes swelling of the organelles and irreversible damage to the cells and tissues in a fatal disease called Pompe disease. I- cell disease or inclusion-cell disease is one of the most severe and rare forms of lysosomal storage disease. In this inherited metabolic disorder, the lysosomes of various cell types do not have most hydrolytic enzymes due to a recessive single gene defect resulting in the accumulation of undigested substrates in the lysosomes. These result in large inclusions in the cells that pathologically affect all organ systems, skeletal integrity, and mental development.