Practice question

N-glycan processing begins in endoplasmic reticulum with en bloc transfer of Glc3Man9GlcNAc2 and trimming to Man8GlcNAc2, but creation of hybrid and complex structures occurs in Golgi. Upon entry to cis-Golgi, alpha-mannosidase I removes four alpha1,2 mannoses yielding compact Man5GlcNAc2, obligate substrate for committed step. In medial-Golgi, GlcNAc transferase I product of MGAT1 is type II membrane protein with short cytosolic tail and large luminal catalytic domain transferring N-acetylglucosamine from UDP-GlcNAc to C2 position of alpha1,3 mannose arm generating GlcNAcMan5GlcNAc2. This addition licenses subsequent mannosidase II removal and GlcNAc transferase II building biantennary structures and future fucosylation. Without enzyme cells cannot synthesize hybrid or complex glycans and accumulate Man5 as in Lec1 CHO mutants and human CDG-IIa with dysmorphism, neurologic deficits, growth retardation, immunodeficiency, coagulopathy, liver dysfunction. Fucosyl, galactosyl and sialyltransferases operate downstream in medial to trans compartments after initiation critical for glycoprotein maturation and signaling integrity throughout tissues and development.