Carbohydrates

Monosaccharides

Carbohydrates are defined as polyhydroxyaldehydes or polyhydroxyacetones, from the simplest carbon skeleton of a trisaccharide, as represented by the Fisher projection for glyceraldehyde and for dihydroxyketone. Thus, carbohydrates are now referred to as aldoses or as ketoses.

Carbohydrates, like amino acids, have a chiral center and, consequently, an optical isomerism, detectable in a polarimeter. Identify the chiral carbon for glyceraldehyde. Also identify whether the model refers to D-glyceraldehyde or L-glyceraldehyde.

To do this, rotate the molecule so that the carbonyl (C=O) is facing down, and with its oxygen atom on the right. If the hydroxyl group (-OH) is on the right of the Jmol screen, it is D-glyceraldehyde. Otherwise, it will be L-glyceraldehyde. It can be seen that the model accessed by the link is of a D-glyceraldehyde.

From these molecules, it is possible to compose several carbohydrates by varying the number of their carbons (diose, triose, tetrose, pentose, hexose, heptose) and/or the function that defines them (aldoses or ketoses). Thus, a glucopyranose molecule can be represented by a glucose

The linear structure represented above is of very low proportion in solution. The most common structure involves a cyclization originating from an initial twist between C-4 and C-5, which brings an alcohol closer to the carbohydrate functional group. In this way, a reaction occurs between the alcohol function and an aldehyde/ketone, producing a hemiacetal (aldehyde + R-OH) or a hemiketal (ketone + R-OH). With the cyclization, the carbohydrate gains another chiral center.

It is worth taking a moment here to consider the acquisition of new models for visualization by Jmol. Up to now, and with rare exceptions, we have used PDB attribute files related to the deposit of crystallographic biomolecules in the homonymous site. Other biomolecules are easily accessible by Jmol itself, by File, Get Mol, which is mirrored to the web by the structures loaded from the Chemapps-Stolaf site.

However, for other molecules, such as those contained in this chapter, the structures are scattered throughout the internet, requiring their download and subsequent loading into Jmol.

Remembering a feature of Jmol, to better understand the concepts reported in this material, in addition to viewing the image related to each subject in a common image program, it is also possible to click and drag the PNG (Portable Network Graphics) image file downloaded from this site to the main Jmol window. This will allow a more consolidated study, since it is possible to observe the molecules in three-dimensional space as was done in the previous chapters, being able to rotate them, direct their observation to a specific region, change colors and representations, calculate distances and angles, among others.

To illustrate what was said, load the model of glucose under ring closure onto your PC, and observe the details of the reaction between the alcohol function and aldehyde that culminates in the production of the hemiacetal.

Is it difficult to visualize? Then try loading the glucose animation under closure model into Jmol

With cyclization, the monosaccharide also acquires a conformational isomerism. Thus, the conformation of a cyclohexane for the pyran ring (e.g. glucose, a pyranose) or furan (e.g. fructose, a furanose) can vary. The main conformers are the boat and the chair, the latter being energetically more favorable.

Reinforcing, both structures can be observed three-dimensionally by lowering them on the PC and dragging one of the images with the mouse to the open Jmol screen. And of course, you can also open the image in the program by File, Open !

It is also possible to visualize the configurational isomerism of carbohydrates using Jmol. To do so, load the alpha configuration of glucose into Jmol. Now position the oxygen in the ring to the North, so that the -CH\(_{2}\)OH function is facing left. Tilt the molecule forward little by little and observe how the alcohol of the anomeric carbon in C1 (just to the right of the oxygen in the ring) is located outside the plane of the ring. This is the \(\alpha\) configuration of glucose.

Repeat the procedure for the beta configuration of fructose, a ketose, to see that the arrangement of the -OH group mentioned is not exactly above the plane, as in the two-dimensional representations of textbooks, although it is quite different from the alpha isomers.

Carbohydrate derivatives

In addition to constitutional isomerism (aldo/keto), optical isomerism (L/D), conformational isomerism (boat/chair), and configurational isomerism (\(\alpha\)/\(\beta\)), monosaccharides can undergo several reactions, such as sulfatation (chondroitin), amination (glucosamine), oxidation, reduction, phosphorylation, methylation, introduction of an alcohol (polyol, “sorbitol.png”) or deoxidation (deoxysugar). These changes enrich the structural and functional diversity of carbohydrates, and are related to variations in the interaction with the solvent, and with other biomolecules, such as those presented in cellular interaction and signaling, among others.

Oligosaccharides

They are defined from an acetal (glycosidic) bond between the anomeric carbons of two monosaccharides. This bond also involves the release of a water molecule. As observed by the model above, the acetal bond is formed between carbons C1 and C4.

The glycosidic bond can also be characterized as \(\alpha\) (ex: maltose) or \(\beta\) (ex: cellobiose) depending on the axial or sagittal vector of a functional group, in this case -OH, from the C1 carbon of the 1st monomer. To highlight this difference, proceed in a similar way to what was done with the glucose molecules above in the text.

First load the maltose. Position the molecule in such a way that the oxygen of the ring of the 1st. residue, the one that has the C1 label on its carbon \(\alpha\), is on the right. Now tilt the structure and highlight how the glycosidic bond moves away from the plane of the 1st residue. This is the bond \(\alpha\), considered in the books as below the two-dimensional plane. Repeat this procedure with cellobiose, and see the difference from a \(\beta\)-glycosidic bond. Note how the bond \(\beta\) occurs in a dimer of cellobiose

In the official nomenclature, oligosaccharides have the numbering of the carbons involved in the glycosidic bond, as well as the direction of the reaction. Thus, we have sucrose, table sugar, or \(\alpha\)-D-glucopyranosyl (1,2)-\(\beta\)-D-fructofuranose, as a disaccharide formed by the acetal bond between a glucose residue and a fructose residue.

Since the glycosidic bond compromises the two anomeric carbons involved in the formation of sucrose, it loses the reducing capacity of the carbonyl group. The same does not occur with lactose, whose glycosidic bond still allows a reducing potential of a free anomer (Cu\(^{+}\) to Cu\(^{0}\), for example).

Clinically, the deficiency of the enzyme \(\beta\)-galactosidase prevents the hydrolysis of the glycosidic bond of lactose, accumulating it in the tissues and inducing one of the forms of lactose malabsorption/intolerance.

In this way, monosaccharides can join together to form disaccharides (maltose), trisaccharides (maltotriose), tetrasaccharides, etc.

Some oligomers of approximately 15-50 units can also exhibit beneficial health properties, being considered functional oligosaccharides. An example of a functional oligosaccharide is inulin, a fructooligosaccharide composed of 30 fructose residues and one glucose residue, and related to digestive, antimicrobial and immunomodulatory benefits.

Polysaccharides

Although there is no consensus on their size, a polysaccharide is considered to be a polymer ranging from 300 to more than 50,000 monomeric residues. These polymers, or glycans, can have the same monomer in their composition, thus being called homoglycans, or different types of monomers, producing heteroglycans.

The most common example of a homoglycan is starch. It is composed of a branched structure and a linear structure. The branched structure is called amylopectin (in the model, shown with 25 glucose residues). See a more concise structure of amylopectin.

Branching occurs in the 1-6 direction between every 10-12 glucose residues. Animal glycogen is similar to amylopectin, except for the greater degree of branching resulting from the spacing of 8-12 glucose residues. Here is a more concise model for rendering the glycogen Rotate the structure (concise or broader model) and notice that there is a central spiral in its molecule. This helical conformation represents amylose. Amylose has a linear structure and presents a helical conformation. Note that both glycogen and starch have this helical structure.

Another common homopolysaccharide is cellulose, a linear polymer of glucose residues. Both amylose and cellulose have conformations resulting from the configuration of their glycosidic bond, \(\alpha\) for amylose and \(\beta\) for cellulose.

Other polysaccharides

Several polysaccharides, homo or hetero, act functionally in cells, such as hyaluronic acid, a heteroglycan of the vitreous humor and synovial fluid, formed by \(\beta\)-acetyl-N-glucosamine and glucuronic acid, or pectin), a water-soluble homopolysaccharide - soluble fiber, present in the plant wall, and formed by galacturonic acid (polygalacturonic), rhamnose, arabinose and galactose.

Other polysaccharides contribute to the constitutive structure of organisms, such as chitin, a structural homoglycan in the exoskeleton of insects and crustaceans, formed by \(\beta\)-acetyl-N-glucosamine residues. Observe a more concise rendered model for chitin. Other polysaccharides also have biological activity, such as heparin, an anticoagulant that acts by chelating calcium ions.