Synthesis of Glycosides, Lactose, Glycoproteins, Glycolipids and Proteoglycans

• Reactions between sugars or the formation of sugar derivatives utilize sugars activated by attachment to nucleotides (a nucleotide sugar).
• UDP-glucose and UDP-galactose are substrates for many glycosyltransferase reactions.
• Lactose is formed from UDP-galactose and glucose.
• UDP-glucose is oxidized to UDP-glucuronate, which forms glucuronide derivatives of various hydrophobic compounds, making them more readily excreted in urine or bile than the parent compound.
• Glycoproteins and glycolipids contain various types of carbohydrate residues.
• The carbohydrates in glycoproteins can be either O-linked or N-linked and are synthesized in the endoplasmic reticulum and Golgi apparatus.
• For O-linked carbohydrates, the carbohydrates are added sequentially (via nucleotide sugar precursors), beginning with a sugar linked to the hydroxyl group of the amino acid side chains of serine or threonine.
• For N-linked carbohydrates, the branched carbohydrate chain is first synthesized on dolichol phosphate and then transferred to the amide nitrogen of an asparagine residue of the protein.
• Glycolipids belong to the class of sphingolipids, synthesized from nucleotide sugars that add carbohydrate groups to the base ceramide.
• Defects in the degradation of glycosphingolipids leads to a class of lysosomal diseases known as the sphingolipidoses.
• Proteoglycans consist of a core protein covalently attached to many long, linear chains of glycosaminoglycans, which contain repeating disaccharide units. Proteoglycans are synthesized in the endoplasmic reticulum and Golgi complex.
• The major carbohydrates in glycosaminoglycans are a hexosamine and uronic acid, along with sulfated carbohydrates.
• Failure to appropriately degrade proteoglycans within the lysosome leads to a set of disorders known as the mucopolysaccharidoses.