Human Biochemistry Volume 2 - Murray R. 1993

Special Topics
Glycoproteins and Proteoglycans
Glycoproteins - I-Cell Disease

As noted above, one of the Functions of the Man-6-P receptor is to recognize and target lysosomal Enzymes to these Organelles. This fact was established through The Study of cultured fibroblasts obtained from patients with I-Cell disease (inclusion-cell disease). I-cell disease is a rare disorder in which cultured Cells lack almost all of their normal lysosomal enzymes, leading to the accumulation of numerous undegraded molecules. At the same time, high activities of lysosomal Enzymes can be detected in serum samples from patients with I-cell disease, suggesting that these enzymes are synthesized in this condition but fail to reach their designated intracellular organelles. Cultured cells from patients are capable of taking up lysosomal enzymes added to the culture medium, indicating that a normal receptor for these enzymes is present in such cells. It has been established that in patients with I-cell disease, lysosomal enzymes are not recognized, whereas in healthy individuals, this recognition function is performed by Man-6-P. The cultured cells of patients are characterized by deficient GlcNAc-phosphotransferase activity, which explains the absence of the Man-6-P marker on the lysosomal enzymes of these cells. Thus, biochemical studies of this disorder have not only elucidated its underlying mechanism but have also significantly advanced our understanding of how Newly synthesized Proteins are targeted to specific organelles, in this case, Lysosomes.