Classification and Structure of Carbohydrates

CLASSIFICATION AND STRUCTURE

Monosaccharides (simple sugars) can be classified according to the number of carbon atoms they contain. Examples of some monosaccharides commonly found in humans are listed in Figure 7.1 . They can also be classified by the type of carbonyl group they contain. Carbohydrates with an aldehyde as their carbonyl group are called aldoses, whereas those with a keto as their carbonyl group are called ketoses (Figure 7.2 ). For example, glyceraldehyde is an aldose, whereas dihydroxyacetone is a ketose. Carbohydrates that have a free carbonyl group have the suffix –ose. [Note: Ketoses have an additional “ul” in their suffix such as xyulose. There are exceptions, such as fructose, to this rule.] Monosaccharides can be linked by glycosidic bonds to create larger structures (Figure 7.3). Disaccharides contain two monosaccharide units, oligosaccharides contain three to ten monosaccharide units, and polysaccharides contain more than ten monosaccharide units and can be hundreds of sugar units in length.

Figure 7.1 Examples of monosaccharides found in humans, classified according to the number of carbons they contain.

Figure 7.2 Examples of an aldose (A) and a ketose (B) sugar.

Figure 7.3 A glycosidic bond between two hexoses producing a disaccharide.

A. Isomers and epimers

Compounds that have the same chemical formula but have different structures are called isomers. For example, fructose, glucose, mannose, and galactose are all isomers of each other, having the same chemical formula, C₆H₁₂O₆. Carbohydrate isomers that differ in configuration around only one specific carbon atom (with the exception of the carbonyl carbon; see “anomers” below) are defined as epimers of each other. For example, glucose and galactose are C-4 epimers because their structures differ only in the position of the –OH group at carbon 4. [Note: The carbons in sugars are numbered beginning at the end that contains the carbonyl carbon (that is, the aldehyde or keto group) as shown in Figure 7.4 .] Glucose and mannose are C-2 epimers. However, because galactose and mannose differ in the position of –OH groups at two carbons (carbons 2 and 4), they are isomers rather than epimers (see Figure 7.4).

Figure 7.4 C-2 and C-4 epimers and an isomer of glucose.

B. Enantiomers

A special type of isomerism is found in the pairs of structures that are mirror images of each other. These mirror images are called enantiomers, and the two members of the pair are designated as a D- and an L-sugar (Figure 7.5). The vast majority of the sugars in humans are D-sugars. In the D isomeric form, the –OH group on the asymmetric carbon (a carbon linked to four different atoms or groups) farthest from the carbonyl carbon is on the right, whereas in the L-isomer, it is on the left. Most enzymes are specific for either the D or the L form, but enzymes known as racemases are able to interconvert D- and L-isomers.

Figure 7.5 Enantiomers (mirror images) of glucose. Designation of D and L is by comparison to the triose, glyceraldehyde. [Note: The asymmetric carbons are shown in green.]

C. Cyclization of monosaccharides

Less than 1% of each of the monosaccharides with five or more carbons exists in the open-chain (acyclic) form in solution. Rather, they are predominantly found in a ring (cyclic) form, in which the aldehyde (or keto) group has reacted with an alcohol group on the same sugar, making the carbonyl carbon (carbon 1 for an aldose, carbon 2 for a ketose) asymmetric. This asymmetric carbon is referred to as the anomeric carbon.

1. Anomers: Creation of an anomeric carbon (the former carbonyl carbon), generates a new pair of isomers, the α and β configurations of the sugar (for example, α-D-glucopyranose and β-D-glucopyranose; see Figure 7.6 ), that are anomers of each other. [Note: In the α configuration, the –OH group on the anomeric carbon projects to the same side as the ring in a modified Fischer projection formula (Figure 7.6A ) and is trans to the CH₂OH group in a Haworth projection formula (Figure 7.6B ). The α and β forms are not mirror images, and they are referred to as diastereomers.] Enzymes are able to distinguish between these two structures and use one or the other preferentially. For example, glycogen is synthesized from α-D-glucopyranose, whereas cellulose is synthesized from β-D-glucopyranose. The cyclic α and β anomers of a sugar in solution spontaneously (but slowly) form an equilibrium mixture, a process known as mutarotation (see Figure 7.6). [Note: For glucose, the α form makes up 36% of the mixture.]

Figure 7.6 A The interconversion (mutarotation) of the α and β anomeric forms of glucose shown as modified Fischer projection formulas. B. The interconversion shown as Haworth projection formulas. [Note: A sugar with a six-membered ring (5C + 1O) is termed a pyranose, whereas one with a five-membered ring (4C + 1O) is a furanose. Virtually all glucose in solution is in the pyranose form.]

2. Reducing sugars: If the hydroxyl group on the anomeric carbon of a cyclized sugar is not linked to another compound by a glycosidic bond, the ring can open. The sugar can act as a reducing agent and is termed a reducing sugar. Such sugars can react with chromogenic agents (for example, the Benedict reagent) causing the reagent to be reduced and colored, with the aldehyde group of the acyclic sugar becoming oxidized. All monosaccharides, but not all disaccharides, are reducing sugars. [Note: Glucose can have its terminal hydroxyl group oxidized to a carboxyl group, forming glucuronic acid, or its aldehyde group oxidized to a hydroxyl group, forming a sugar alcohol.]

A colorimetric test can detect a reducing sugar in urine. A positive result is indicative of an underlying pathology, because sugars are not normally present in urine, and can be followed up by more specific tests to identify the reducing sugar.

D. Joining of monosaccharides

Monosaccharides can be joined to form disaccharides, oligosaccharides, and polysaccharides. Important disaccharides include lactose (galactose + glucose), sucrose (glucose + fructose), and maltose (glucose + glucose). Important polysaccharides include branched glycogen (from animal sources) and starch (plant sources) and unbranched cellulose (plant sources). Each is a polymer of glucose. The bonds that link sugars are called glycosidic bonds. These are formed by enzymes known as glycosyltransferases that use nucleotide sugars such as uridine diphosphate glucose as substrates.

1. Naming glycosidic bonds: Glycosidic bonds between sugars are named according to the numbers of the connected carbons and with regard to the position of the anomeric hydroxyl group of the sugar involved in the bond. If this anomeric hydroxyl is in the α configuration, the linkage is an α-bond. If it is in the β configuration, the linkage is a β-bond. Lactose, for example, is synthesized by forming a glycosidic bond between carbon 1 of β-galactose and carbon 4 of glucose. The linkage is, therefore, a β(1→4) glycosidic bond (see Figure 7.3 ). [Note: Because the anomeric end of the glucose residue is not involved in the glycosidic linkage, it (and, therefore, lactose) remains a reducing sugar.]

E. Complex carbohydrates

Carbohydrates can be attached by glycosidic bonds to noncarbohydrate structures, including purine and pyrimidine bases (found in nucleic acids), aromatic rings (such as those found in steroids and bilirubin), proteins (found in glycoproteins and proteoglycans), and lipids (found in glycolipids), to form glycosides.

1. N- and O-glycosides: If the group on the noncarbohydrate molecule to which the sugar is attached is an –NH₂ group, the structure is an N-glycoside, and the bond is called an N-glycosidic link. If the group is an –OH, the structure is an O-glycoside, and the bond is an O-glycosidic link (Figure 7.7 ). [Note: All sugar–sugar glycosidic bonds are O-type linkages.]

Figure 7.7 Glycosides: examples of N- and O-glycosidic bonds.