About half of all proteins in the human body are glycoproteins. The substances play a role as cell components as well as immune substances. They are formed primarily as part of what is known as N-glycosylation and can cause serious diseases if incorrectly assembled.
What are glycoproteins?
Glycoproteins are proteins with tree-like branched heteroglycan residues. They are usually of viscous consistency. The macromolecules contain covalently bonded sugar groups. They consist of monosaccharides, such as glucose, fructose, mannose or acetylated amino sugars. Therefore, they are also called protein-bound oligosaccharides. Covalent binding can occur in different ways and corresponds to binding to either the amino acids serine or asparagine. Binding to serine is called O- and binding to asparagine is called N-glycosylation. The glycoproteins of N-glycosylation vary in size. They correspond to monosaccharides, di- or oligosaccharides up to polysaccharides. According to their proportion of monosaccharides, they are divided into mannose-rich, complex and hybrid glycoproteins. In the mannose-rich group, mannose residues predominate. In the complex group, saccharides predominate. The hybrid group is a mixed form. The carbohydrate content of glycoproteins ranges from a few percent for ribonucleases to up to 85 percent for blood group antigens.
Function, action, and roles
Glycoproteins perform numerous functions in the human organism. They are a structural component of cell membranes and are also referred to as structural proteins in this context. However, they are also present in mucus and serve as lubricants in fluids. They contribute to cell interaction as membrane proteins. Some glycoproteins also fulfill hormonal functions, such as the growth factor hCG. They are equally important as immunological components in the form of immunoglobulins and interferons. All export proteins and membrane proteins of the body were still glycoproteins, at least during biosynthesis. They are particularly relevant for recognition reactions in the immune system because they interact with immunological T cells and T cell receptors. Various plasma proteins have been isolated in human blood plasma, of which only albumin and prealbumin lack sugar residues. The abundance of glycoproteins is surprising. Ultimately, almost all extracellular soluble proteins and enzymes have residues of sugar. As hormones, glycoproteins have pleiotropic effects and are thus crucial for the activity of various organ systems. For example, the hormones TSH, HCG, and FSH are glycoproteins. As membrane protienes, they are represented in the role of receptor as well as in that of transport controller and stabilizer. They have a stabilizing effect mainly together with glycolipids. Together with these substances, they form the so-called glycocalyx, which stabilizes cell wall-less cells.
Formation, occurrence, properties, and optimal values
The most common form of formation of glycoproteins is N-glycosidic binding or N-glycosylation to asparagine. Sugar binds to the nitrogen of free acid amide groups in this process. N-glycosylation takes place in the endoplasmic reticulum. The N-glycosides formed in this way are the most relevant glycoprotein group. During N-glycosylation, the sugar precursor snythetizes to the carrier molecule dolichol in independence of the amino acid sequence of the target protein. The OH group at the end of the molecule is linked to diphosphate. An oligosaccharide precursor is formed at the terminal phosphate residue of the molecules. The first seven of the sugars assemble on the cytosolic side. Two N-acetyl glucosamines and five manose residues are attached to the dolichol phosphate. The sugar nucleotides GDP-mannose and UDP-N-acetyl-glucosamine appear as donors. The precursor is transported across the ER membrane by a transport protein. Thus, the precursor is oriented to the inner side of the endoplasmic reticulum, where four mannose residues are added to it. In addition, glucose residues are added. The 14 sugar long precursor is finally transferred to a protein. Another formation pathway for glycoproteins is O-glycosidic binding or O-glycosylation to serine, which is carried out in the Golgi apparatus of cells. In this process, the binding of the sugar takes place to a hydroxyl group of serine. Values for glycoproteins are primarily relevant in relation to plasma protein, as they play a role in a large blood count.To list all standard values for glycoproteins individually at this point would go beyond the scope.
Diseases and disorders
Some genetic diseases show effects on glycosylation. One group of such disorders is CDG. In this case, the glycoproteins show abnormal levels. Affected individuals suffer from slowed development that relates to both physical and mental issues. Strabismus can be another symptom of the genetic disorder. In total, about 250 different genes are involved in the formation of glocoproteins. In congenital glycosylation disorders, disorders in the attachment of carbohydrate side chains to proteins are present due to a genetic disposition. In post-translational modification, proteins acquire their full functionality. When this process abnormally assembles enzymes or proteins that build carbohydrate side chains, CDG results. N-glycosylation is most commonly affected by disruption. To date, about 30 enzyme defects have been discovered that affect N-glycosylation. Genetic O-glycosylation disorders are somewhat less common. They manifest in neuromuscular multisystem disorders, such as Walker-Warburg syndrome. Because glycoproteins perform so many functions in the organism, the clinical picture is characterized by multiple symptoms. All organ systems can be affected by congenital glycosylation disorders. Psychomotor developmental disorders are the leading symptom. Neurological abnormalities are just as frequent. Coagulation disorders or endocrine disorders are also not uncommon.
