ASPARAGINE-LINKED OLIGOSACCHARIDE BIOSYNTHESIS

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Previous studies of asparagine-linked oligosaccharide synthesis in Chinese Hamster Ovary Cells have demonstrated that glucose-starvation leads to abnormal synthesis of asparagine-linked oligosaccharides due to abnormal lipid-linked oligosaccharide synthesis. It is the aim of this proposal to further investigate the nature in the defect in lipid-linked oligosaccharide synthesis in these cells and, in addition, investigate the possibility that glycoprotein processing is altered under conditions of glucose starvation or excess glucose. A second system to be investigated for alterations in asparagine-linked oligosaccharide synthesis is the BB/W diabetic rat. Diabetes, which is characterized by a deficiency of insulin, which leads to the inability of some tissues to take up glucose, and to excess glucose uptake by tissues insulin independent for glucose uptake. These investigations will focus on glycosylation alterations in liver and skeletal muscle, in order to determine whether glucose starvation or excess glucose can affect the regulation of asparagine-linked oligosaccharide synthesis in vivo under physiological conditions. Since abnormal glycolylation can lead to altered functional properties of some glycoproteins, the results of this study will provide information about key regulatory points in asparagine-linked oligosaccharide synthesis, and should be useful for future studies of altered glycoprotein synthesis or functions in diabetes or other systems where abnormal glucose concentrations occur.