We begin our consideration of carbohydrates with monosaccharides, the simplest carbohydrates. These simple sugars serve not only as fuel molecules but also as fundamental constituents of living systems. For instance, DNA has a backbone consisting of alternating phosphoryl groups and deoxyribose, a cyclic five-carbon sugar.

Monosaccharides are aldehydes or ketones that have two or more hydroxyl groups. The smallest monosaccharides, composed of three carbons, are dihydroxyacetone and d- and l-glyceraldehyde.

Dihydroxyacetone is called a ketose because it contains a keto group (shown in red), whereas glyceraldehyde is called an aldose because it contains an aldehyde group (also shown in red). They are referred to as trioses (tri- for “three,” referring to the three carbon atoms that they contain). Similarly, simple monosaccharides with four, five, six, or seven carbon atoms are called tetroses, pentoses, hexoses, or heptoses, respectively. Perhaps the monosaccharides of which we are most aware are the hexoses glucose and fructose. Glucose is an essential energy source for virtually all forms of life. Fructose is commonly used as a sweetener that is converted into glucose derivatives inside the cell.

Carbohydrates can exist in a dazzling variety of isomeric forms (Figure 10.1). Dihydroxyacetone and glyceraldehyde are constitutional isomers because they have identical molecular formulas but differ in how the atoms are ordered. Stereoisomers are isomers that differ in spatial arrangement. Glyceraldehyde has a single asymmetric carbon atom, and, thus, there are two stereoisomers of this sugar: d-glyceraldehyde and l-glyceraldehyde. These molecules are a type of stereoisomer called enantiomers, which are mirror images of each other.

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Monosaccharides made up of more than three carbon atoms have multiple asymmetric carbon atoms, and so they exist not only as enantiomers but also as diastereoisomers, isomers that are not mirror images of each other. According to convention, the d and l isomers are determined by the configuration of the asymmetric carbon atom farthest from the aldehyde or keto group.

Figure 10.2 shows the common sugars that we will see most frequently in our study of biochemistry. d-Ribose, the carbohydrate component of RNA, is a five-carbon aldose, as is deoxyribose, the monosaccharide component of DNA. d-Glucose, d-mannose, and d-galactose are abundant six-carbon aldoses. Note that d-glucose and d-mannose differ in configuration only at C-2, the carbon atom in the second position. Sugars that are diastereoisomers differing in configuration at only a single asymmetric center are epimers. Thus, d-glucose and d-mannose are epimeric at C-2; d-glucose and d-galactose are epimeric at C-4. Note that ketoses have one less asymmetric center than aldoses with the same number of carbon atoms. d-Fructose is the most abundant ketohexose.

The predominant forms of ribose, glucose, fructose, and many other sugars in solution are not open chains. Rather, the open-chain forms of these sugars cyclize into rings. The chemical basis for ring formation is that an aldehyde can react with an alcohol to form a hemiacetal.

For an aldohexose such as glucose, the same molecule provides both the aldehyde and the alcohol: the C-1 aldehyde in the open-chain form of glucose reacts with the C-5 hydroxyl group to form an intramolecular hemiacetal (Figure 10.3). The resulting cyclic hemiacetal, a six-membered ring, is called pyranose because of its similarity to pyran.

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Similarly, a ketone can react with an alcohol to form a hemiketal.

The C-2 keto group in the open-chain form of a ketohexose, such as fructose, can form an intramolecular hemiketal by reacting with either the C-6 hydroxyl group to form a six-membered cyclic hemiketal or the C-5 hydroxyl group to form a five-membered cyclic hemiketal (Figure 10.4). The five-membered ring is called a furanose because of its similarity to furan.

The depictions of glucopyranose (glucose) and fructofuranose (fructose) shown in Figures 10.3 and 10.4 are Haworth projections. In such projections, the carbon atoms in the ring are not written out. The approximate plane of the ring is perpendicular to the plane of the paper, with the heavy line on the ring projecting toward the reader.

We have seen that carbohydrates may contain many asymmetric carbon atoms. An additional asymmetric center is created when a cyclic hemiacetal is formed, generating yet another diastereoisomeric form of sugars called anomers. In glucose, C-1 (the carbonyl carbon atom in the open-chain form) becomes an asymmetric center. Thus, two ring structures can be formed: α-d-glucopyranose and β-d-glucopyranose (Figure 10.3). For d sugars drawn as Haworth projections in the standard orientation as shown in Figure 10.3, the designation α means that the hydroxyl group attached to C-1 is below the plane of the ring; β means that it is above the plane of the ring. The C-1 carbon atom is called the anomeric carbon atom. An equilibrium mixture of glucose contains approximately one-third α anomer, two-thirds β anomer, and <1% of the open-chain form.

The furanose-ring form of fructose also has anomeric forms, in which α and β refer to the hydroxyl groups attached to C-2, the anomeric carbon atom (Figure 10.4). Fructose forms both pyranose and furanose rings. The pyranose form predominates in fructose free in solution, and the furanose form predominates in many fructose derivatives (Figure 10.5).

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β-d-Fructopyranose, found in honey, is one of the sweetest chemicals known. The β-d-fructofuranose form is not nearly as sweet. Heating converts β-fructopyranose into β-fructofuranose, reducing the sweetness of the solution. For this reason, corn syrup with a high concentration of fructose in the β-d-fructopyranose form is used as a sweetener in cold, but not hot, drinks.

Hayworth projections provide simple means of depicting carbohydrates, but they are misleading in suggesting that the molecules are planar. For instance, stereochemical rendering of the six-membered pyranose ring shows that it is not planar, because of the tetrahedral geometry of its saturated carbon atoms. Instead, pyranose rings adopt two classes of conformations, termed “chair” and “boat” because of their resemblance to these objects (Figure 10.6). In the chair form, the substituents on the ring carbon atoms have two orientations: axial and equatorial. Axial bonds are nearly perpendicular to the average plane of the ring, whereas equatorial bonds are nearly parallel to this plane. Axial substituents sterically hinder each other if they emerge on the same side of the ring (e.g., 1,3-diaxial groups). In contrast, equatorial substituents are less crowded.

Although both the α and β chair form of d-glucopyranose exist in solution, the chair form of β-d-glucopyranose predominates because all axial positions are occupied by hydrogen atoms. The bulkier −OH and −CH₂OH groups emerge at the less hindered periphery. The boat form of glucose is disfavored because it is quite sterically hindered.

The biochemical properties of monosaccharides can be modified by reaction with other molecules. These modifications increase the biochemical versatility of carbohydrates, enabling them to serve as signal molecules or facilitating their metabolism. Three common reactants are alcohols, amines, and phosphates. A bond formed between the anomeric carbon atom of glucose and the oxygen atom of an alcohol is called a glycosidic bond—specifically, an O-glycosidic bond—and the resulting product is called a glycoside. O-Glycosidic bonds are prominent when carbohydrates are linked together to form long polymers and when they are attached to proteins. In addition, the anomeric carbon atom of a sugar can be linked to the nitrogen atom of an amine to form an N-glycosidic bond. Carbohydrates can also form an ester linkage to phosphates, one of the most prominent modifications in carbohydrate metabolism. For instance, the phosphorylation of glucose is essential when glucose metabolizes to yield ATP (Chapter 16). Examples of modified carbohydrates are shown in Figure 10.7.

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