The third chains of living organisms—a trail of glycobiology that started from the third floor of building 4 in NIH

• Published in: Archives of Biochemistry and Biophysics 2004-06, Vol.426 (2), p.107-121
• Main Author: Kobata, Akira
• Format: Article
• Language: English
• Subjects: ABO Blood-Group System - chemistry; ABO Blood-Group System - classification; ABO Blood-Group System - metabolism; Aging; Animals; Blood Grouping and Crossmatching - methods; Carbohydrate Sequence; Endo-β- N-acetylglucosaminidases; Exoglycosidases; Glycoproteins; Glycoproteins - chemistry; Glycoproteins - classification; Glycoproteins - metabolism; Glycosylation; Human chorionic gonadotropin; Humans; Hydrazinolysis; Lectin column chromatography; Lewis Blood-Group System - chemistry; Lewis Blood-Group System - classification; Lewis Blood-Group System - metabolism; Milk - chemistry; Molecular Sequence Data; N-linked sugar chains; Oligosaccharides - chemistry; Oligosaccharides - classification; Oligosaccharides - metabolism; Structure-Activity Relationship; γ-Glutamyltranspeptidase
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2004.01.023

Application of a finger-printing method to the analysis of human milk oligosaccharides led to the finding that several oligosaccharides were missing in the milk of non-secretor or Lewis-negative individuals. This finding helped us in opening the door of elucidating the enzymatic basis of blood types in human. Based on these successful studies, a strategy to establish reliable techniques to elucidate the structures and functions of the N-linked sugar chains of glycoproteins was devised. It was to contrive enzymatic and chemical means to release quantitatively the N-linked sugar chains as oligosaccharides, and finger-print them by using appropriate methods to demonstrate the sugar pattern of a glycoprotein. These methods enabled us to determine that the N-linked sugar chains of glycoproteins can be classified into three subgroups: high mannose-type, complex-type, and hybrid-type. By comparative studies of the sugar patterns of a glycoprotein produced by different organs and different animals, occurrences of organ- and species-specific glycosylation were found in many glycoproteins. By comparative studies of the glycosylation patterns of the subunits constructing human chorionic gonadotropin and other glycoproteins, occurrence of site-directed N-glycosylation was also found, indicating that the processing and maturation of the N-linked sugar chains of a glycoprotein might be controlled by the structure of polypeptide moiety. Furthermore, these methods enabled us to elucidate the structural alteration of the sugar chains of a glycoprotein induced by diseased state of the producing cells, such as rheumatoid arthritis and malignancy. Recent studies of glycoproteins in the brain-nervous system through aging revealed that N-glycosylation of P 0 in the rat spinal cord is induced by aging. Therefore, glycobiology is expanding tremendously into fields such as pathological and gerontological research.