**2. Importance of membrane glycoconjugates in providing the functional activity of leukocytes**

Experimental studies have shown that cells of the immune system are exposed to the direct and indirect effects of high blood glucose concentrations in patients with diabetes [4, 5]. Glucose metabolism pathways are activated under conditions of hyperglycemia include the autooxidation of glucose, caused glycation of long-lived proteins; the hexosamine pathway, which leads to the glycosylation of hydroxyl-containing amino acid residues; sorbitol metabolism, accompanied by the formation of free radical; and oxidative phosphorylation leading to mitochondria electron transport chain intensification and the generation of superoxide-anion radicals [12, 13]. Glucose autooxidation and glycation of proteins and lipids leads to an accumulation of advanced oxidation protein products and advanced glycation end products (AGEs), which are difficult to eliminate from the blood and remain in circulation [14]. They are also the source of reactive oxygen species (ROS) since they imitate metal containing oxidation systems. Excessive formation of ROS and reactive nitrogen species (RNS) leads to the development of oxidative-nitrative

#### *The Structure of Leukocyte Sialic Acid-Containing Membrane Glycoconjugates is a Differential… DOI: http://dx.doi.org/10.5772/intechopen.97199*

stress [15]. These changes create a favorable background for the formation of micro- and macrovascular diabetic complications [15, 16].

In condition of hyperglycemia, leukocytes are preactivated by ROS and RNS, angiotensin II, and AGEs. The interaction of AGEs with their receptors, RAGE, causes intracellular signal transduction, which leads to changes in gene expression, overproduction of free radicals, the release of pro-inflammatory molecules (tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), IL-2, IL-6 etc.), and changes in the activity of intracellular enzymes [17].

Glycosyltransferases and glycosidases, which involved in the synthesis of glycans of glycoconjugates, pay much interest among cellular enzymes [18]. In general, mammalian glycans are the product of several types of glycohydrolases and dozens of glycosyltransferases, which act sequentially in the process of oligosaccharide chains synthesis. Each of the glycosyltransferases uses one type of sugar substrate and forms a specific bond between one monosaccharide and a glycan precursor. Thus, the set of glycosyltransferases in the cell determines what type of glycans, among the large number of possible structures, will be formed [19].

The variety of monosaccharides is very large, but most often the carbohydrate components of glycoconjugates of eukaryotic cells include glucose (Glc), N-acetylglucose (GlcNAc), galactose (Gal), N-acetylgalactose (GalNAc), mannose (Man), N-acetylneuraminic acid (Neu5Ac), also known as sialic acid (Sia). Different monosaccharides, combined in a specific sequence by glycosyltransferases, form a glycan, which at one end attaches to a protein or lipid molecule. The formed glycoconjugates are the main macromolecular constituents of biomembranes [19, 20].

The diversity of glycans attached to proteins and lipids makes it possible to form unique glycoconjugates with a wide range of cellular functions. Glycoconjugates play an important role in various biological processes, in particular, glucose homeostasis, protein quality control, cellular differentiation, adhesion, intercellular signaling and inflammation. It is known that carbohydrate residues increase the solubility of glycoproteins, protect against proteolysis, influence on their folding, intracellular transport and secretion. Glycoconjugates are components of the glycocalyx, providing specific interactions with ligands, intercellular contacts and communication. Glycans of glycoconjugate are involved in the formation of the immune response, blood clotting and provide the individuality of organisms and their plasticity [20].

The immune system is highly controlled and fine-tuned by glycosylation, through the addition of a variety of glycans to virtually all adhesion molecules and receptors of leukocytes. Glycoconjugates are implicated in fundamental cellular and molecular processes. Glycans perform function of molecular recognition that regulates both stimulatory and inhibitory immune pathways [21]. The presence of modified carbohydrate determinants in the glycan structure modifies the biological activity of the entire glycoconjugate. The interaction of specific ligand with its modified receptor leads to violations at the level of transmembrane and intracellular signaling [22]. In according to the importance of glycans in the immune system, scientific researches emphasize the essential contributions of glycosylation in the regulation of innate and adaptive immune responses [21]. Therefore, today the scientists (biochemists, molecular biologists, immunologists, pathologists and pharmacologists) are making the great efforts to explore the interrelations of carbohydrate determinants with their glycobiology. Establishing changes in the glycans structure of membrane glycoconjugates of immunocompetent cells makes it possible to understand the mechanism of pathological changes in condition of diabetes and diabetic complications.

#### *Fundamentals of Glycosylation*

Thus, changes in intracellular metabolism, intensification of glycation processes and the development of oxidative-nitrative stress in blood cells under conditions of prolonged hyperglycemia are the main factors that induce pathological changes in the structure of their components and affect their functional state [12, 20].
