title: Glycosylation site occupancy in health, congenital disorder of glycosylation and fatty liver disease.
abstract: Glycosylation is an integral part in health and disease, as emphasized by the growing number of identified glycosylation defects. In humans, proteins are modified with a diverse range of glycoforms synthesized in complex biosynthetic pathways. Glycosylation disorders have been described in congenital disorders of glycosylation (CDG) as well as in acquired disease conditions such and non-alcoholic fatty liver disease (NAFLD). A hallmark in a subset of CDG cases is the reduced glycosylation site occupancy of asparagine-linked glycans. Using an optimized method protocol, we determined the glycosylation site occupancy from four proteins of hepatic and lymphatic origin from CDG and NAFLD patients. We found variable degrees of site occupancy, depending on the tissue of origin and the disease condition. In CDG glycosylation sites of IgG2 and IgA1 were occupied to normal levels. In NAFLD haptoglobin and transferrin glycosylation sites were hyper-glycosylated, a property qualifying for its use as a potential biomarker. Furthermore, we observed, that glycosylation sites of liver-originating transferrin and haptoglobin are differentially occupied under physiological conditions, a further instance not noticed in serum proteins to date. Our findings suggest the use of serum protein hyperglycosylation as a biomarker for early stages of NAFLD.
authors.affiliation: Institute of Physiology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Hülsmeier
authors.affiliation: Division of Metabolism and Molecular Pediatrics, University Children's Hospital Zürich, Steinwiesstrasse 75, 8032 Zürich, Switzerland.
authors.forename: Micha
authors.initials: M
authors.lastname: Tobler
authors.affiliation: Division of Metabolism and Molecular Pediatrics, University Children's Hospital Zürich, Steinwiesstrasse 75, 8032 Zürich, Switzerland.
authors.forename: Patricie
authors.initials: P
authors.lastname: Burda
authors.affiliation: Institute of Physiology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Hennet
mesh_terms: D015415:Biomarkers / Q000097:blood; D018981:Congenital Disorders of Glycosylation / Q000097:blood* / Q000150:complications; D005260:Female; D006031:Glycosylation; D006242:Haptoglobins / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000209:etiology
chemical_list: D015415:Biomarkers; D006242:Haptoglobins; D007070:Immunoglobulin A; D007074:Immunoglobulin G