Jos Jansen

1 Introduction to hepatic congenital glycosylation disorders 11 Demannosylation with subsequent galactosylation and sialylation are steps that ultimately result in formation of the complete glycoprotein. Figure 1. Overview of the glycosylation pathway and CDG due to defective steps in this pathway. Enzymesmarked in red are known CDG. Derived fromH.H. Freeze, Genetic Disorders of Glycosylation, 2015(15) The secretory pathway The secretory pathway is composed of organelles that serve a common purpose, namely excretion and sorting of newly synthesized proteins. The lies adjacent to the nucleus where nascent proteins are folded and checked for improper folding. If folded incorrectly, the protein is removed from the ER by the ER associated degradation (ERAD) mechanism.(16) The ER is also the organelle where a new protein potentially receives the N-glycan, forming a glycoprotein. When the new protein passes quality criteria, it buds of and travels towards the ER-to-Golgi-intermediate compartment (ERGIC) via coatomer protein complex (COP)II vesicles. In the ERGIC the faith of the protein is decided.(17) Most proteins will traffic to and fuse with the Golgi. Others will go to lipid droplets, the plasma membrane or other organelles. The Golgi is where modifications of the glycoprotein takes place. The Golgi is composed of different stacks with a clear topology: an ER-orientated cis- part; a medial part; and a trans -part (or TGN,