Are galactosamine and galactose glycoproteins

The sugar pool in the part-time job

Complex N-glycans can also be fucosylated at the base of the N-acetyl-D-glucosamine. This core fucosylation of IgG antibodies is extremely relevant for the extent of antibody-mediated cell cytotoxicity (ADCC), which is determined today for every antibody used in oncology.

O-glycosylations modify serine or threonine residues. They are more complex and less explored than N-glycosylations. So far, no fixed amino acid sequence is known for the O-glycosidically bound carbohydrates. The first carbohydrate linked to the amino acid is either N-acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc), mannose (Man), fucose (Fuc), or glucose (Glc) (Figure 5). A special kind of O-glycosylation is located inside the cell and here even inside the cell nucleus. The modification of histones with O-GlcNAc residues is a variant of the histone code that helps regulate gene expression.

Glycosylation as a border and protease protection

In most cases, extracellular proteins are glycosylated. The hydrophilic glycans, which are mostly acidic due to the negatively charged sialic acids, contribute significantly to the water solubility of the proteins. It is probably only through these modifications that the remarkably high protein concentrations in human blood plasma of around 50 to 70 mg / ml become possible. In addition, the negatively charged sialic acids of the glycoconjugates and the sulfate and carboxylate residues of the glycosaminoglycans give the cells their negative surface charge and define critical diffusion barriers.

The dense layer of mucins, which is deposited on many epithelia, for example of the respiratory tract and the intestine, functions as a critical barrier and protects the organism against invasion by microorganisms. If these layers are interrupted, for example due to genetic defects, this can have very serious consequences such as recurrent inflammation and an increased risk of cancer.

The barrier function is supported by the fact that the mucins, which are densely packed with O-glycans, are clearly protected against cleavage by proteases. In fact, extensive segments of some mucins cannot even be cleaved by the much experimentally used proteinase K. The protection that strong glycosylation offers against proteases is also used specifically for drugs, for example the erythropoietin derivative darbepoetin alfa.

In addition, the sugar modifications give the mucins their important lubricating function. The importance of this property becomes clear when failures occur. Patients whose salivary gland function is impaired by radiotherapy or by Sjogren's syndrome suffer from significant functional problems in the head and neck area and problems with eating due to difficult swallowing. One also thinks of the critical lubricating function of hyaluronan, a high molecular weight polysaccharide in connective tissue, in body fluids such as the synovial fluid in the joint cavities and in the tear fluid of the eye. Here deficits have to be replaced therapeutically.

Incorrect glycosylation: cause of disease