title: Metabolic alteration of the N-glycan structure of a protein from patients with a heterozygous protein deficiency.
abstract: Glycosylation, an important post-translation modification, could alter biological activity or influence the clearance rates of glycoproteins. We report here the first example of a heterozygous protein deficiency leading to metabolic alteration of N-glycan structures in residual secreted protein. Analysis of C1 esterase inhibitor (C1INH) glycans from normal individuals and patients with hereditary deficiency of C1INH demonstrated identical O-glycan structures but the N-glycans of patients with a heterozygous genetic deficiency were small, highly charged and lacked sialidase releasable N-acetylneuraminic acid. Structural studies indicate that the charge character of these aberrant N-glycan structures may result from the presence of mannose-6-phosphate residues. These residues might facilitate secretion of C1INH through an alternate lysosomal pathway, possibly serving as a compensatory mechanism to enhance plasma levels of C1INH in these deficient patients.
authors.affiliation: Department of Chemical and Biochemical Engineering, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Fuming
authors.initials: F
authors.lastname: Zhang
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Bries
authors.forename: Sybil C
authors.initials: SC
authors.lastname: Lang
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: David W
authors.initials: DW
authors.lastname: Murhammer
authors.forename: John M
authors.initials: JM
authors.lastname: Weiler
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D000799:Angioedema / Q000235:genetics* / Q000378:metabolism; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D019075:Electrophoresis, Capillary; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011488:Protein Deficiency / Q000235:genetics*; D012016:Reference Values; D015843:Serpins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D011134:Polysaccharides; C469952:SERPING1 protein, human; D015843:Serpins; D009439:Neuraminidase; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D019158:N-Acetylneuraminic Acid