Gaucher disease pathway. In relation to Gaucher’s disease, initial results of enzymatic complementation were disappointing, but the reason for this was soon established. Crude enzyme preparations obtained from human tissues such as the placenta were not taken up by non?parenchymal hepatic cells. This occurred because the enzyme preparations did not harbour the appropriate glycoprotein targeting sequences for uptake by membrane receptors leading to delivery to the nascent organelle.
Mannosephosphate Gaucher disease pathway residues are typically found on nascent lysosomal membranes, and are components of the pathway for endogenous and exogenous delivery of a large class of lysosomal proteins. This pathway is not in fact the relevant pathway for delivery of nascent glucocerebrosidase, which is a lysosomal membrane protein. Later, with the discovery of the macrophage mannose receptor, deglycosylation of purified preparations of human tissue glucocerebrosidase to reveal terminal mannose residues was successful in facilitating uptake of the enzyme molecules by enriched populations of macrophages.
