Figure 1.

(a) The structure of Glc₃Man₉GlcNAc₂-pyrophosphate-dolichol. This compound is essentially the only LLO found in normal human fibroblasts. However, appreciable amounts of this material are also found in all CDG-I fibroblasts reflecting the “leaky” nature of the mutations in these patients. Based on animal studies, total lack of this LLO is not compatible with life. (b) The structure of Man₉GlcNAc₂-pyrophosphate-dolichol. This is one of the major LLOs found in CDG-If. The accumulation of this compound implies a defect in the addition of Glc in α1,3 linkage to the Man at the arrow. Since the synthesis of Dol-P-Glc and the activity of the relevant Dol-P-Glc–dependent α1,3-glucosyltransferase are both normal in CDG-If, the defect has been attributed to an inability to utilize Dol-P-Glc. (c) The structure of Man₅GlcNAc₂-pyrophosphate-dolichol. This is the other major LLO found in CDG-If. The accumulation of this compound implies a defect in the addition of four Man residues to the Man at the arrow by four Dol-P-Man–dependent mannosyltransferases. Since the synthesis of Dol-P-Man and the activities of the relevant mannosyltransferases are normal in CDG-If, the defect has been attributed to an inability to utilize Dol-P-Man.