Biochemistry - The Chemical Reactions of Living Cells, Volume 1 - D. Metzler 1980

The Molecules We Are Made Of
Sugars and Polysaccharides
Structure and Properties of Sugars

Sugars are classified into polyoxyaldehydes (aldoses) and polyoxyketones (ketoses). The carbonyl group is highly reactive; a typical reaction is The addition of electron-rich groups, specifically the —OH group (Chapter 7, Section 3). If the sugar chain is sufficiently long (4–6 carbon atoms), one of the hydroxyl groups of the same molecule can add to the carbonyl group, forming a cyclic hemiacetal—a ring form that exists in equilibrium with the free aldehyde or ketone form [Equation (2-10)]. The six-membered rings formed in this way (pyranose rings) are particularly stable, although five-membered furanose rings are also found in some CARBOHYDRATES. The natural tendency of five- and six-carbon sugars (pentoses and hexoses) towards cyclization ensures The formation of stable polymers from highly reactive, unstable monomers.

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Upon sugar cyclization, a new chiral center is created at the carbon atom (the anomeric carbon atom) that was previously part of the carbonyl group. The two configurations with respect to this atom are designated as the a- and ß-configurations [Equation (2-10)]. The equilibrium for most sugars is shifted toward the formation of cyclic forms. Thus, for glucose at 25°C in Water, the equilibrium mixture contains ∼0.02% free aldehyde, 38% a-pyranose form, 62% ß-pyranose form, and less than 0.5% of each of the much less stable furanose forms. Although Polysaccharides are generally composed of cyclic residues, open-chain forms sometimes serve as metabolic intermediates.

Sugars contain multiple chiral centers, and various diastereomers are given different names. For example, glucose, mannose, and galactose are simply three of the eight possible diastereomeric aldohexoses (the others are allose, altrose, gulose, idose, and talose) [6]. Each of these sugars is represented by a pair of enantiomers—D and L, which are mirror images of each other. Fisher projection formulas (Section A.4) are frequently used to illustrate the relationships among sugars, as shown in Fig. 2-13. While projection formulas are convenient for comparing sugar structures, they provide a rather vague representation of their three-dimensional Structure. According to Fisher's convention, vertical bonds at each carbon atom should be viewed as projecting away behind that atom. In reality, a molecule cannot adopt such a conformation. Compare, for instance, the three-dimensional structure of ribitol (Section A.6), formed by the reduction of glucose, with its Fisher formula.

FIG. 2-13. Structural formulas of certain sugars (Monosaccharides) according to Fisher's convention.

Monosaccharides belong to the D- or L-form depending on the configuration at the chiral center furthest removed from the carbonyl group (Fig. 2-13). If, in a sugar molecule oriented according to Fisher's convention, the —OH group at this carbon atom is on the right, the sugar is classified in the D-family. The simplest of all chiral sugars is glyceraldehyde.

The cyclic forms of sugars are often also depicted in accordance with Fisher's convention. For example, a-D-glucopyranose looks like this:

In this method of depiction, the hydroxyl group at the anomeric carbon atom in the a-form of the D-sugar family is on the right, whereas in the L-sugar family it is on the left. Thus, a-D-glucopyranose and a-L-glucopyranose are enantiomers.

To simplify the depiction of cyclic sugar configurations, Haworth structural formulas are frequently employed:

The lower part of the ring (bold lines) should be visualized as projecting toward the observer, while the opposite edge lies behind the plane of the drawing. Haworth structures are relatively easy to draw and unambiguously indicate the configuration, but they do not reflect the relative spatial arrangement of the groups attached to the ring. For this reason, conformational formulas, shown in Fig. 2-14, are frequently used.

Most sugars adopt a chair conformation in which the majority of substituent groups occupy equatorial positions. D-aldoses typically exhibit the "Cl" conformation (p. 108), whereas L-aldoses are characterized by a different chair form (the "1C" form). There are exceptions to this rule; for instance, a-D-idopyranose appears to adopt the 1C conformation. It is also worth noting that in sugar rings, an axial orientation is often preferred for substituent groups at the anomeric carbon atom [35].

FIG. 2-14. Structure of certain cyclic sugars that make up polysaccharides.

Reduction of the carbonyl group of a sugar (e.g., with sodium borohydride) yields a sugar alcohol, such as ribitol (Section A.6) or sorbitol [which is obtained by the reduction of glucose; Equation (11-8)]. The aldehyde groups of aldoses can be oxidized by a multitude of Reagents to yield carboxylic acids known as aldonic acids. This accounts for the reducing character of aldoses. For example, in an alkaline medium, aldoses reduce monovalent copper ions to cuprous oxide, silver ions to free metal, and ferricyanide to ferrocyanide. The latter reaction can serve as the basis for a sensitive analytical method. Even considering that aldoses predominantly exist in hemiacetal forms [Equation (2-10)], their reducing properties are quite apparent. While reduction by metal-containing reagents typically proceeds via the Formation of the free aldehyde, oxidation with hypobromite (Br₂ in an alkaline medium) leads to the formation of a lactone, as observed, for example, in the enzymatic reaction described by Equation (a), Table 8-4.

Many sugar derivatives occur in nature. Among these are aldonic acids [e.g., 6-phosphogluconic acid; Equation (9-12)] as well as uronic acids containing a terminal —COOH group (at position 6 of glucuronic acid; Fig. 2-14). The —OH group at position 2 of the glucose molecule can be replaced by a —NH₂ group to yield 2-amino-2-deoxyglucose, commonly referred to as glucosamine (GlcN), or by a —NH—CO—CH₃ group to yield N-acetylglucosamine

(GlcNAc). Similar derivatives exist for other sugars. In many polysaccharides, sulfate groups are attached to the sugar units via ester linkages.

Two 6-deoxy sugars (lacking oxygen at the C-6 atom)—rhamnose and fucose¹—are widely distributed. Both possess an "unnatural" L-configuration, although metabolically they are derived from D-glucose and D-mannose, respectively.

¹ This type of compound is also referred to as 5-methylpentose. — Note added by Ed.