A journey to the world of glycobiology

Finding of the deletion phenomenon of certain oligosaccharides in human mil k and its correlation to the blood types of the donors opened a way to eluc idate the biochemical basis of blood types in man. This success led to the idea of establishing reliable techniques to elucidate the structures and fu nctions of the N-linked sugar chains of glycoproteins. N-Linked sugar chain s were first released quantitatively as oligosaccharides by enzymatic and c hemical means, and labelled by reduction with (NaBH4)-H-3. After fractionat ion, structures of the radioactive oligosaccharides were determined by a se ries of methods developed for the studies of milk oligosaccharides. By usin g such techniques, structural rules hidden in the N-linked sugar chains, an d organ- and species-specific N-glycosylation of glycoproteins, which affor ded a firm basis to the development of glycobiology, were elucidated. Findi ng of galactose deficiency in the N-linked sugar chains of serum lgG from p atients with rheumatoid arthritis, and malignant alteration of N-glycosylat ion in various tumors opened a new research world called glycopathology. However, recent studies revealed that several structural exceptions occur i n the sugar chains of particular glycoproteins. Finding of the occurrence o f the Gal beta1-4Fuc alpha1- group linked at the C-6 position of the proxim al N-acetylglucosamine residue of the hybrid type sugar chains of octopus r hodopsin is one of such examples. This finding indicated that the fucosyl r esidue of the fucosylated trimannosyl core should no more be considered as a stop signal as has long been believed. Furthermore, recent studies on dys troglycan revealed that the sugar chains, which do not fall into the curren t classification of N- and O-linked sugar chains, are essential for the exp ression of the functional role of this glycoprotein. It was found that expression of many glycoproteins is altered by aging. Amo ng the alterations of the glycoprotein patterns found in the brain nervous system, the most prominent evidence was found in P-0. This protein is produ ced in non-glycosylated form in the spinal cord of young mammals. However, it starts to be N-glycosylated in the spinal cord of aged animals. These evidences indicate that various unusual sugar chains occur as minor c omponents in mammals, and play important roles in particular tissues.