MCAT Biochemistry Review

Chapter 4: Carbohydrate Structure and Function

4.3 Monosaccharides

Monosaccharides contain alcohols and either aldehydes or ketones. As such, these functional groups undergo the same reactions that they do when present in other compounds. These include oxidation and reduction, esterification, and nucleophilic attack (creating glycosides).

OXIDATION AND REDUCTION

One of the most important biochemical reactions in the human body is the oxidation of carbohydrates in order to yield energy. As monosaccharides switch between anomeric configurations, the hemiacetal rings spend a short period of time in the open-chain aldehyde form. Just like other aldehydes, they can be oxidized to carboxylic acids; these oxidized aldoses are called aldonic acids. Because aldoses can be oxidized, they are considered reducing agents. Therefore, any monosaccharide with a hemiacetal ring is considered a reducing sugar. When the aldose in question is in ring form, oxidation yields a lactone instead—a cyclic ester with a carbonyl group persisting on the anomeric carbon, as shown in Figure 4.11. Lactones, such as vitamin C, play an essential role in the human body.

Figure 4.11. Lactone Contains a cyclic ester.

Two standard reagents are used to detect the presence of reducing sugars: Tollen's reagent and Benedict's reagent. Tollen's reagent utilizes Ag(NH3)2+ as an oxidizing agent. In a positive Tollen's test, aldehydes reduce Ag+ to metallic silver. When Benedict's reagent is used, the aldehyde group of an aldose is readily oxidized, indicated by a red precipitate of Cu2O, as demonstrated in Figure 4.12. To test specifically for glucose, one may utilize the enzyme glucose oxidase, which does not react with other reducing sugars. A more powerful oxidizing agent, such as dilute nitric acid, will oxidize both the aldehyde and the primary alcohol (on C-6) to carboxylic acids.

Figure 4.12. Positive Test for an Aldose Using Benedict's Reagent Aldoses will react, forming copper(II) oxide; ketones may react more slowly.

An interesting phenomenon is that ketose sugars are also reducing sugars and give positive Tollen's and Benedict's tests. Although ketones cannot be oxidized directly to carboxylic acids, they can tautomerize to form aldoses under basic conditions, via ketoenol shifts. While in the aldose form, they can react with Tollen's or Benedict's reagents to form the carboxylic acid. Tautomerization refers to the rearrangement of bonds in a compound, usually by moving a hydrogen and forming a double bond. In this case, the ketone group picks up a hydrogen while the double bond is moved between two adjacent carbons, resulting in an enol: a compound with a double bond and an alcohol group.

Reduced sugars also play an essential role in human biochemistry. When the aldehyde group of an aldose is reduced to an alcohol, the compound is considered an alditol. A deoxy sugar, on the other hand, contains a hydrogen that replaces a hydroxyl group on the sugar. The most well-known of these sugars is D-2-deoxyribose, the carbohydrate found in DNA.

ESTERIFICATION

Because carbohydrates have hydroxyl groups, they are able to participate in reactions with carboxylic acids and carboxylic acid derivatives to form esters, as shown in Figure 4.13.

Figure 4.13. Esterification of Glucose Acetic anhydride used as carboxylic acid derivative.

In the body, esterification is very similar to the phosphorylation of glucose, in which a phosphate ester is formed. Phosphorylation of glucose is an extremely important metabolic reaction of glycolysis in which a phosphate group is transferred from ATP to glucose, thus phosphorylating glucose while forming ADP, as shown in Figure 4.14. Hexokinase (or glucokinase, in the liver and pancreatic β-islet cells) catalyzes this reaction.

Figure 4.14. Phosphorylation of Glucose

BRIDGE

The action of hexokinase and glucokinase (as well as all the key glycolytic enzymes) is discussed in Chapter 9 of MCAT Biochemistry Review.

GLYCOSIDE FORMATION

Hemiacetals react with alcohols to form acetals. The anomeric hydroxyl group is transformed into an alkoxy group, yielding a mixture of α- and β-acetals (with water as a leaving group). The resulting carbon–oxygen (C–O) bonds are called glycosidic bonds, and the acetals formed areglycosides. An example is the reaction of glucose with ethanol shown in Figure 4.15. Equivalent reactions happen with hemiketals, forming ketals.

Figure 4.15. Glycosidic Linkage Formation Hemiacetal (or hemiketal) sugars react with alcohols under acidic conditions to form acetals (or ketals).

Disaccharides and polysaccharides form as a result of glycosidic bonds between monosaccharides. Glycosides derived from furanose rings are referred to as furanosides and those derived from pyranose rings are called pyranosides. Note that glycoside formation is a dehydration reaction; thus, breaking a glycosidic bond requires hydrolysis.

MCAT Concept Check 4.3:

Before you move on, assess your understanding of the material with these questions.

1.    Explain the difference between esterification and glycoside formation.

2.    From a metabolic standpoint, does it make sense for carbohydrates to get oxidized or reduced? What is the purpose of this process?