Synthesis of substrates in N-glycan biosythesis Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein Authored: Dall'Olio, GM, 2009-11-10 Edited: Jassal, B, 2009-11-10 GENE ONTOLOGYGO:0006488 N-linked glycosylation commences with the 14-step synthesis of a dolichol lipid-linked oligosaccharide (LLO) consisting of 14 sugars (2 core GlcNAcs, 9 mannoses and 3 terminal GlcNAcs). This pathway is highly conserved in eukaryotes, and a closely related pathway is found in many eubacteria and Archaea. Mutations in the genes associated with N-glycan precursor synthesis lead to a diverse group of disorders collectively known as Congenital Disorders of Glycosylation (type I and II) (Sparks et al, 1993). The phenotypes of these disorders reflect the important role that N-glycosylation has during development, controlling the folding and the properties of proteins in the secretory pathway, and proteins that mediate cell-to-cell interactions or timing of development. Pubmed20301507 Reactome Database ID Release 43446193 Reactome, http://www.reactome.org ReactomeREACT_22433 Reviewed: Gagneux, P, 2010-04-16 PathwayStep3127 PathwayStep3128 PathwayStep3125 PathwayStep3126 PathwayStep3122 PathwayStep3121 PathwayStep3124 PathwayStep3123 PathwayStep3120 PathwayStep3118 PathwayStep3119 PathwayStep3114 PathwayStep3115 PathwayStep3116 PathwayStep3117 Addition of a third glucose to the N-glycan precursor by an ALG10 homologue Addition of a second glucose to the N-glycan precursor by ALG8 Addition of the second N-acetyl-glucosamine to the N-glycan precursor Addition of N-acetyl-D-glucosamine to Dolichyl phosphate Addition of the first glucose to the N-glycan precursor by ALG6 Addition of the last mannose to the N-glycan precursor by ALG3, inside the ER lumen. Flipping of the N-glycan precursor to inside the ER Addition of the sixth mannose to the N-glycan precursor by ALG3. Addition of the seventh mannose to the N-glycan precursor by ALG9, inside the ER lumen Addition of the eighth mannose to the N-glycan precursor by ALG12, inside the ER lumen Addition of the first mannose to the N-glycan precursor by ALG13/14 Addition of a second mannose to the N-glycan precursor by ALG2 Addition of a third mannose to the N-glycan precursor by ALG2 Addition of a fourth and fifth mannose to the N-glycan precursor by ALG11