Biochemistry Of Glycoprotein

Glycoprotein

INTRODUCTION Glycoprotein is 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.

The plasma membrane surrounds the eukaryotic cell. Glycoproteins—proteins bonded to carbohydrates—allow for the detection of foreign cells, such as invading bacteria. GLYCOSYLATION Glycosylation is the process or result of addition of saccharides to proteins and lipids. CLASSIFICATION There are two major types of glycoproteins based on their structure and the mechanism of synthesis: N-linked glycoproteins and O-linked glycoproteins.

Glycoprotein

N-linked Glycoprotein

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synthesized and modified within two membrane-bound organelles in the cell, the rough endoplasmic reticulum and the Golgi apparatus. important for the folding of some eukaryotic proteins. The N-linked glycosylation process occurs in eukaryotes and widely in Achaea, but very rarely in bacteria. 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. the specific order of the amino acids in the polypeptide is critical to its function and is referred to as the amino acid sequence

The twenty different amino acids can be used for the synthesis of polypeptides. One of the twenty amino acids used for the synthesis of polypeptides, asparagine (C4H8N2O3), 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 some other amino acid and then a serine or threonine residue follows the asparagine (-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.

Glycoprotein

O-linked Glycoproteins 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 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.

Glycoprotein

THE EIGHT SUGARS CONTAINED IN GLYCOPROTEINS

Glycoprotein

BIOFUNCTION Function Structural molecule

Description Collagen Many of the viruses with helical internal structure have outer coverings (also known as envelopes) composed of lipoprotein or glycoprotein, or both.

Lubricant and protective agent

Mucin

Transport molecule

Transferrin (for iron ion delivery), ceruloplasmin (carries 90% of the copper in our plasma)

Immunologic molecule

Immunoglobins, histocompatibility antigens

Hormone

Chorionoic gonadotropin (to prevent the disintegration of the corpus luteum of the ovary and thereby maintain progesterone production that is critical for a pregnancy in humans). thyroid-stimulating hormone (TSH)

Enzyme

Various, e.g. alkaline phosphatase

Cell attachment-recognition site

Various proteins involved in cell-cell (e.g. sperm-oocyte), virus-cell, bacterium-cell, and hormone cell interactions Prion, an infectious agent that does not contain any nucleic acid but rather an abnormal form of a glycoprotein. HIV infects certain human cells by binding its envelope glycoproteins gp120 and gp41 to specific molecules on the surface of the cells. Only cells that carry the appropriate molecules are susceptible to infection by HIV.

Antifreeze

Certain plasma proteins of coldwater fish

Interact with specific carbohydrates

Lectins, selectins (cell adhesion lectins), antibodies

Receptor

Various proteins involved in hormone and drug action

Glycoprotein

Affect folding of certain proteins

Calnexin, calreticulin Creutzfeldt-Jakob Disease; The gene for the normal glycoprotein is on the short arm of chromosome 20, and mutations of this gene have been shown to have a dominant inheritance, that is, are likely to be inherited. About 15 per cent of cases of CJD are inherited.

Regulation of development

Notch (highly conserved cell signalling system present in most multicellular organisms) and its analogs, key proteins in development. Glycoprotein laminin controls the growth of axons within the central nervous system.

Homeostasis (and thrombosis)

Specific glycoproteins on the surface membranes of platelets. Cobalamin, or vitamin B12, one of the most recently isolated vitamins, is necessary in minute amounts for the formation of nucleoproteins, proteins, and red blood cells, and for the functioning of the nervous system. Cobalamin deficiency is often due to the inability of the stomach to produce a glycoprotein (intrinsic factor), which aids in the absorption of this vitamin.