| This drawing illustrates the formation of N-glycans within cells. N-glycans (the structure on the train caboose) are built up by the consecutive addition of sugar bricks that are provided underway. These bricks are called GDP-mannose (GPD-Man), dolichol- phosphate-mannose (Dolichol-P-Man) and dolichol-phosphate-glucose (Dolichol-P-Glc). The enzymes PMM and PMI participate to the formation of GDP-Man (see top of drawing). Deficiencies in PMM or PMI, as found in CDG-Ia and Ib, cause a shortage of GDP-Man and of Dol-P-Man, thereby leading to an incomplete construction of N-glycans. In CDG -Ic, the ALG6 glucosyltransferase enzyme (see the little guy with the fancy helicopter in the middle of the drawing) is not working properly.
ALG6 and two other glucosyltransferases are necessary for the addition of three glucose bricks on the N-glycan tree. These three glucose bricks are required for the transfer of N-glycans onto proteins (the truck) by the enzyme oligosaccharyltransferase (the OTase crane). |
Drawing provided by Dr. Thierry Hennet.