Glycoproteins are proteins that contain covalently attached sugar residues. The hydrophilic and polar characteristics of sugars may dramatically change the chemical characteristics of the protein to which they are attached. The addition of sugars is often required for a glycoprotein to function properly and reach its ultimate destination in the cell or organism. Glycoproteins are frequently present at the surface of cells where they function as membrane proteins or as part of the extracellular matrix. These cell surface glycoproteins play a critical role in cell–cell interactions and the mechanisms of infection by bacteria and viruses.
There are three types of glycoproteins based on their structure and the mechanism of synthesis: N-linked glycoproteins, O-linked glycoproteins, and nonenzymatic glycosylated glycoproteins.
N-linked glycoproteins are synthesized and modified within two membrane-bound organelles in the cell, the rough endoplasmic reticulum and the Golgi apparatus. The protein component of the glycoprotein is assembled on the surface of the rough endoplasmic reticulum by the sequential addition of amino acids, creating a linear polymer of amino acids called a polypeptide . Twenty different amino acids can be used for the synthesis of polypeptides. The specific order of the amino acids in the polypeptide is critical to its function and is referred to as the amino acid sequence. One of the twenty amino acids used for the synthesis of polypeptides, asparagine (C 4 H 8 N 2 O 3 ), is essential for the synthesis of N-linked glycoproteins.
N-linked glycoproteins have carbohydrates attached to the R side chain of asparagine residues within a polypeptide. The carbohydrate is always located in amino acid sequences, where the asparagine is followed by some other amino acid and then a serine or threonine residue (-Asn-Xaa-Ser/Thr). Carbohydrate is not attached to the polypeptide one sugar at a time. Rather, a large preformed carbohydrate containing fourteen or more sugar residues is attached to the asparagine as the protein is being translated in the rough endoplasmic reticulum. The carbohydrate on the glycoprotein is then modified by enzymes that remove some sugars and attach others as the newly formed glycoprotein moves from the rough endoplasmic reticulum to the Golgi apparatus and other locations in the cell. Many N-linked glycoproteins eventually become part of the cell membrane or are secreted by the cell.
O-linked glycoproteins are usually synthesized by the addition of sugar residues to the hydroxyl side chain of serine or threonine residues in polypeptides in the Golgi apparatus. Unlike N-linked glycoproteins, O-linked glycoproteins are synthesized by the addition of a single sugar residue at a time. Many O-linked glycoproteins are secreted by the cell to become a part of the extracellular matrix that surrounds it.
Nonenzymatic glycosylation or glycation creates glycoproteins by the chemical addition of sugars to polypeptides. Since this type of glycosylation is nonenzymatic, the factors that control glycosylation are simply time and the concentration of sugar. Older proteins are more glycosylated, and people with higher circulating levels of glucose experience higher levels of nonenzymatic glycosylation. This is the basis of the glycosylated hemoglobin A1c diagnostic test used for the monitoring and long-term maintenance of blood sugar levels in diabetics.
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Voet, Donald; Voet, Judith G.; and Pratt, Charlotte W. (2002). Fundamentals of Biochemistry, updated edition. New York: Wiley.