Discuss the stereochemistry of monosaccharides, nucleotides and amino acids

In the α form, the hydroxyl group (blue) is on the opposite side of the ring to the CH3OH group, whereas in the β it is on the same side.

The cyclic form of pyranose sugars also has the ‘boat’ and ‘chair’ stereoisomers, which refers to the shape of the ring structure as shown in the diagram below:

The chair form (left) is more thermodynamically stable since there is less steric hindrance between the oxygen atoms, although both forms exist in nature.

Two monosaccharide monomers can form a glycosidic bond between the anomeric carbon of one monosaccharide and a hydroxyl group on the other (usually that attached to carbon 4 or 6) to create a disaccharide. The stereochemistry of the monosaccharides affects the disaccharide that is formed – for example maltose and cellubiose are composed of two glucose monosaccharides, however maltose uses α-glucose whereas cellubiose uses the β form. This leads to a different special arrangement of the glucose residues as shown below:

As shown in the diagram, the β-1,4-glycosidic bond between the glucose residues in cellubiose causes the two rings to be alternately flipped, whereas in maltose they are aligned in the same orientation.

A similar effect is seen in the polymers formed from the α and β forms of glucose – many α glucose residues linked by glycosidic bonds forms starch, a storage polysaccharide in many plant cells, whereas many β glucose residues form cellulose, a major structural component of plant cell walls due to its rigidity.

This diagram also shows clearly the alternating alignment of the β glucose residues in cellulose.

These differences are key for the different roles of each polymer. Starch coils up because of the shape of the α glycosidic bond, causing it to form compact granules suitable for energy storage. Cellulose forms straight chains which hydrogen bond to each other, creating strong and rigid microfibrils to form the cell walls of plant cells.

Nucleotides

Nucleotides are the individual monomer units which make up the polymer DNA. The pentose sugar, being a monosaccharide, can exist in both the α and β forms to form similar structures to glucose. Since the base of the nucleotide is attached to the first carbon of the pentose sugar by a glycosidic bond, nucleotides can exist in both α and β forms – although the naturally occurring form is β. Since the two antiparallel chains of nucleotide residues hydrogen bond to each other very specifically, due to the structure of the bases, changing the orientation of the bases by using the α form nucleotides would prevent the structure coiling up correctly into a double helix.

The structure of DNA formed from β nucleotides is given below:

It is clear that changing the glycosidic bond to an α form would cause the bases to be orientated differently and not align correctly with the corresponding base on the opposite strand. This would prevent correct replication and transcription of the DNA – thus explaining why this form is not seen in living organisms.

Amino Acids

Like monosaccharides, amino acids are categorised into D and L enantionmers. However, almost all naturally occurring amino acids are in the D form. The two stereoisomers are shown in the diagram below:

If you visualise looking at the 3D molecule from the position of the hydrogen atom, the CORN rule can be used to identify the D and L forms – in the L form the word ‘CORN’ is spelt clockwise about this viewpoint (where CO refers to the carboxylic acid group, R refers to the side group and N refers to the amino group).

Since the enzymes used in protein synthesis and hydrolysis are specific to the L form of amino acids in most organisms, D stereoisomers cannot be used in most natural biological systems.

Many amino acid residues are linked by peptide bonds to form polypeptide chains, which fold further to form proteins. The L form of amino acids would cause the polypeptide chains to fold up differently since the R groups would be differently positioned in space – for example an α-helix formed from L-amino acids is right handed whereas one formed from D-amino acids is left handed. Therefore, the protein would not have the same precise 3D structure and so not function in the same way as one composed of L amino acids.

The peptide bonds can be in either cis or trans forms – this is because the peptide bond has 40% double bond character due to the delocalisation of electrons over the C=O and C-N bonds. This causes the bond to become more rigid and planar by restricting rotation. Since biological protein synthesis is stereospecific due to the specificity of the enzymes, in biological proteins the trans form is almost always seen, which reduces steric hindrance between the sidechains of adjacent residues. Diagrams illustrating the peptide bond and the two stereoisomers of a dipeptide are shown below:

Conclusion

Monosaccharides, nucleotides and amino acids all have different stereoisomers which can significantly affect the structure of a polymer formed from their residues. In some situations, for example many polysaccharides, both stereoisomers will exist in nature and their different structures and properties exploited for different functions. For others, for example nucleotides, only one stereoisomer can exist in nature since the other cannot perform a suitable cellular function.