Introduction to Carbohydrates Carbohydrates are: 1. The primary energy reservoir in the biosphere. 2. Biosynthetic precursors to amino acids and nucleic acids. 3. Allow for targeting of proteins for trafficking within the cell. 4. Structural uses: • Cell walls in plants • Cell walls in bacteria • Exoskeletons in insects and arthropods Structural Hierarchy: 1. Monosaccharides: cannot be hydrolyzed to simpler sugars. 2. Oligosaccharides: 'a few' covalently linked monosaccharides. 3. Polysaccharides: 'many' covalently linked monosaccharides. Note that in contrast to proteins and nucleic acids, which are linear polymers, extensive branching can exist in polysaccharides.

Monosacchardes

All carbons in monosaccharides are 'hydrated' -hence the name carbohydrate (general formula (CH2O)N). 1. The simplest monosaccharides contain three carbons: dihydroxyacetone and glyceraldehyde. 2. When the C=O group is at the 2nd position it's called an ketose, such as in dihydroxyacetone. 3. When the C=O group is at the very end it's an aldose, such as in glyceraldehyde. 4. Note that the aldose, glyceraldehyde, has a chiral center and therefore exists in D and L forms, or mirror images of each other. The D-form is the "root" compound for all other naturally occurring aldoses, i.e. all aldoses have the same chirality at this carbon. 5. Additional hydrated carbons (HO-C-H) are added just below the aldehyde or ketone group. Therefore, the chiral center of D- glyceraldehyde is preserved. The added carbon generates a new chiral center. The two different molecules generated by the addition of another carbon are called epimers because they differ in only

one chiral center. For example, the addition of a CH2OH unit to D- glyceraldehyde gives the following two epimers: erythrose and threose.

The carbon ketose (dihydroxyacetone) and the two possible three carbon aldoses, D- and L-glyceraldehyde are shown. Dihydroxyacetone has no chiral center. The middle carbon in glyceraldehyde is chiral; the D- form is most prevalent in biochemical systems. The addition of a H-C-OH group below the aldehyde group of glyceraldehyde generates either erythrose or threose, depending on the chirality of the newly added carbon. Since the fourth carbon in these compounds originated from D-glyceraldehyde, they both have the same chirality.

This process is continued, generating five- and six-carbon aldoses.

The generation of five- and six-carbon aldoses is shown. The new H-C-OH group is inserted below the aldehyde group, generating two possible configurations of the new chiral center. All of these compounds have inherited the chiral center from D-glyceraldehyde, thus these are all D-sugars. The four chiral centers on glucose (which are also present on the other C6 aldoses) are colored red. The five carbon aldose, ribose, plays an important role in nucleic acid (e.g. RNA) structure. The six carbon aldose, glucose, plays an important role in metabolism as well as in forming structural materials; cellulose is principally made of glucose.

Larger ketoses are generated from dihydroxyacetone using the same approach:

Generation of Ketoses. Two four carbon ketoses are possible by the addition of a H-C-OH group to dihydroxyacetone. One has the same chirallity as in D-glyceraldehyde. The addition of two additional carbons generates the six carbon ketose fructose, an important intermediate in biochemical pathways.

Carbon Number. Carbons are numbers begining with the end that is close to the carbonyl group. Thus in aldoses the carbon bearing the aldehyde group is "1" while in ketoses, the carbon bearing the keto group is "2". Configuration of monosaccharides in solution - ring formation: In general, alcohols can attack the C=O group in sugars to form hemiacetals. Since sugars have OH groups, they can form hemiacetals by an intramolecular reaction, forming closed rings. Only long (>C4) saccharides can form stable internal hemiacetals, giving closed rings.

Conformation of Ring Structures Since there are no double bonds in sugars, there is free rotation about each bond. Although the necessity to form a ring constrains possible torsion angles, pyranose and furanose rings can adopt multiple conformations. In the case of pyranoses, there are two stable "chair" forms, which interconvert via a higher-energy "boat" form:

Conformational state of β-glucose. Chair form I converts to the boat form by bond rotations that raise the anomeric carbon. The boat form can then convert to chair form II by bond rotations that lower carbon 4. The groups attached to the carbons can assume two different positions with respect to the axis of the ring. Axial groups (blue) point up or down, while equatorial groups (magenta) point outward. In the case of β-glucose chair form I is more stable because all of the bulky groups are equatorial. The intermediate boat form is higher in energy than both chair forms due to distortion of bond angles and molecular crowding.

Modified Sugars Deoxy-sugars: loss of the 2'-OH group: e.g.DNA versus RNA

N-acetyl glucosamine (NAG, found in cartilage and bacterial cell walls)

N-acetylmuramic acid (NAM, found in bacterial cell walls)

Oxidation of Aldoses Aldoses, which bear a terminal carboxyl group, can be easily oxidized to the corresponding carboxylic acid by weak oxidizing agents, such as silver ion (Ag+). Consequently, these sugars are referred to as reducing sugars:

Oxidation of glucose to gluconic acid by silver ions.

Ketoses, such as fructose, cannot be readily oxidized to the acid and are called non-reducing sugars.

In the case of di- and poly-saccahrides, the end with the free carboxyl group is generally referred to as the non-reducing end, even if it happens to be a ketose.