GLYCOSIDIC BOND: CHARACTERISTICS, TYPES AND NOMENCLATURE - BIOLOGY - 2025

The glycosidic bonds are covalent bonds that occur between sugars (carbohydrates) and other molecules which may be other monosaccharides or other molecules of a different nature. These links make possible the existence of multiple fundamental components for life, not only in the formation of reserve fuels and structural elements, but also of information-carrying molecules essential for cellular communication.

The formation of the polysaccharides depends fundamentally on the establishment of the glucosidic bonds between the free alcohol or hydroxyl groups of the individual monosaccharide units.

Example of glycosidic binding in Glycogen (Source: Glykogen.svg-NEUROtikerderivative-work-Marek-M-Public-domain via Wikimedia Commons)

However, some complex polysaccharides contain modified sugars that are attached to small molecules or groups such as amino, sulfate, and acetyl through glucosidic bonds, and that do not necessarily involve the release of a water molecule by a condensation reaction. These modifications are very common in glycans present in the extracellular matrix or glycocalyx.

Glycosidic linkages occur in multiple cellular contexts, including the binding of the polar head group of some sphingolipids, essential constituents of the cell membranes of many organisms, and the formation of glycoproteins and proteoglycans.

Important polysaccharides such as cellulose, chitin, agar, glycogen, and starch would not be possible without glycosidic bonds. Likewise, protein glycosylation, which occurs in the endoplasmic reticulum and in the Golgi complex, is extremely important for the activity of many proteins.

Numerous oligo- and polysaccharides function as glucose reservoirs, as structural components, or as adhesives for cell attachment in tissues.

The relationship between glycosidic bonds in oligosaccharides is analogous to that of peptide bonds in polypeptides and to phosphodiester bonds in polynucleotides, with the difference that there is greater diversity in glycosidic bonds.

characteristics

The glycosidic bonds are much more varied than their analogues in proteins and nucleic acids, since in principle any two sugar molecules can join each other in many ways, because they have multiple -OH groups that can participate in the formation of the link.

Furthermore, isomers of monosaccharides, that is, one of the two orientations that the hydroxyl group can have in the cyclic structure relative to the anomeric carbon, provide an additional level of diversity.

Isomers have different three-dimensional structures, as well as different biological activities. Cellulose and glycogen consist of repeating D-glucose units but differ in the type of glycosidic bond (α1-4 for glycogen and β1-4 for cellulose), and therefore have different properties and functions.

Just as polypeptides have a polarity with an N- and a C- end, and polynucleotides have 5 'and 3' ends, oligo- or polysaccharides have a polarity defined by the reducing and non-reducing ends.

The reducing end has a free anomeric center that does not form a glycosidic bond with another molecule, thus retaining the chemical reactivity of the aldehyde.

The glycosidic bond is the most flexible region of an oligo- or polysaccharide moiety, since the structural saddle conformation of individual monosaccharides is relatively rigid.

Formation of the glycosidic bond

The glycosidic bond can join two monosaccharide molecules through the anomeric carbon of one and the hydroxyl group of the other. That is, the hemiacetal group of one sugar reacts with the alcohol group of another to form an acetal.

In general, the formation of these bonds occurs by condensation reactions, where a water molecule is released with each bond that is formed.

However, in some reactions oxygen does not leave the sugar molecule as water, but as part of the diphosphate group of a uridine diphosphate nucleotide.

The reactions that give rise to the glycosidic bonds are catalyzed by a class of enzymes known as glycosyltransferases. They are formed between a sugar modified covalently by the addition of a phosphate group or a nucleotide (Glucose 6-phosphate, UDP-galactose, for example) that binds to the growing polymer chain.

Hydrolysis of the glycosidic bond

Glycosidic bonds can be easily hydrolyzed in slightly acidic environments, but they are quite alkaline resistant.

The enzymatic hydrolysis of the glycosidic bonds is mediated by enzymes known as glycosidases. Many mammals do not have these enzymes for the degradation of cellulose, so they are not able to extract energy from this polysaccharide, despite being an essential source of fiber.

Ruminants such as cows, for example, have bacteria associated with their intestines that produce enzymes capable of degrading the cellulose they ingest, which makes them capable of taking advantage of the energy conserved in plant tissues.

The enzyme lysozyme, produced in the tears of the eye and by some bacterial viruses, is capable of destroying bacteria thanks to its hydrolytic activity, which breaks the glycosidic bond between N-acetylglucosamine and N-acetylmuramic acid in the cell wall of bacteria.

Diversity

Oligosaccharides, polysaccharides or glycans are very diverse molecules and this is due to the many ways in which monosaccharides can join each other to form higher order structures.

This diversity is based on the fact, as mentioned above, that sugars have hydroxyl groups that allow different binding regions, and that bonds can occur between the two possible stereoisomers with respect to the anomeric carbon of the sugar (α or β).

Glycosidic bonds can be formed between a sugar and any hydroxy compound such as alcohols or amino acids.

In addition, a monosaccharide can form two glycosidic bonds, so it can serve as a branch point, introducing potential complexity in the structure of glycans or polysaccharides in cells.

Types

As far as types of glycosidic bonds are concerned, two categories can be differentiated: the glycosidic bonds between monosaccharides that make up the oligo- and polysaccharides, and the glycosidic bonds that occur in the glycoproteins or glycolipids, which are proteins or lipids with portions of carbohydrates.

O-glucosidic bonds

O-glycosidic bonds occur between monosaccharides, are formed by the reaction between the hydroxyl group of one sugar molecule and the anomeric carbon of another.

Disaccharides are among the most common oligosaccharides. Polysaccharides have more than 20 monosaccharide units linked together in a linear fashion and sometimes have multiple branches.

Example of O-glycosidic bond (Source: Tpirojsi via Wikimedia Commons)

In disaccharides such as maltose, lactose, and sucrose, the most common glycosidic bond is the O-glucosidic type. These bonds can occur between the carbons and -OH of the α or β isomeric forms.

The formation of glycosidic bonds in oligo- and polysaccharides will depend on the stereochemical nature of the sugars that are attached, as well as on their number of carbon atoms. Generally, for sugars with 6 carbons, linear bonds occur between carbons 1 and 4 or 1 and 6.

There are two main types of O-glycosides which, depending on the nomenclature, are defined as α and β or 1,2-cis and 1,2-trans-glycosides.

1,2-cis glycosylated residues, α-glycosides for D-glucose, D-galactose, L-fucose, D-xylose or β-glycosides for D-mannose, L-arabinose; as well as 1,2-trans (β-glycosides for D-glucose, D-galactose and α-glycosides for D-mannose, etc.), are of great importance for many natural components.

O-glycosylation

One of the most common post-translational modifications is glycosylation, which consists of the addition of a carbohydrate portion to a growing peptide or protein. Mucins, secretory proteins, can contain large amounts of oligosaccharide chains linked by O-glucosidic bonds.

The O-glycosylation process occurs in the Golgi complex of eukaryotes and consists of the binding of proteins to the carbohydrate portion through a glycosidic bond between the -OH group of an amino acid residue of serine or threonine and the anomeric carbon. of sugar.

The formation of these bonds between carbohydrates and hydroxyproline and hydroxylysine residues and with the phenolic group of tyrosine residues has also been observed.

N-glycosidic bonds

N-glycosidic bonds are the most common among glycosylated proteins. N-glycosylation occurs mainly in the endoplasmic reticulum of eukaryotes, with subsequent modifications that can occur in the Golgi complex.

Example of N-glycosidic bond (Source: Tpirojsi, via Wikimedia Commons)

N-glycosylation depends on the presence of the consensus sequence Asn-Xxx-Ser / Thr. The glycosidic bond occurs between the amide nitrogen of the side chain of asparagine residues and the anomeric carbon of the sugar that binds to the peptide chain.

The formation of these bonds during glycosylation depends on an enzyme known as oligosacaryltransferase, which transfers oligosaccharides from a dolichol phosphate to the amide nitrogen of the asparagine residues.

Other types of glycosidic bonds

S-glucosidic bonds

They also occur between proteins and carbohydrates, they have been observed between peptides with N-terminal cysteines and oligosaccharides. Peptides with such bonds were initially isolated from proteins in human urine and erythrocytes bound to glucose oligosaccharides.

C-glucosidic bonds

They were observed for the first time as a post-translational modification (glycosylation) in a tryptophan residue in RNase 2 present in human urine and in RNase 2 of erythrocytes. A mannose is attached to the carbon at position 2 of the indole nucleus of the amino acid via a C-glucosidic bond.

Nomenclature

The term glycoside is used to describe any sugar whose anomeric group is replaced by a group -OR (O-glycosides), -SR (thioglycosides), -SeR (selenoglycosides), -NR (N-glycosides or glucosamines) or even -CR (C-glucosides).

They can be named in three different ways:

(1) replacing the terminal "-o" of the name of the corresponding cyclic form of the monosaccharide by "-ido" and before writing, as a different word, the name of the substituent R group.

(2) using the term "glycosyloxy" as a prefix to the monosaccharide name.

(3) using the term O-glycosyl, N-glycosyl, S-glycosyl or C-glycosyl as a prefix for the name of the hydroxy compound.

References

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