25.8 Disaccharides

Disaccharides are carbohydrates made of two monosaccharide units joined by a glycosidic bond. The type of glycosidic linkage and the identity of the monosaccharides determine whether a disaccharide is reducing or non-reducing, how it behaves in solution, and what biological role it plays.

This section covers four key disaccharides: maltose, cellobiose, lactose, and sucrose.

Disaccharide Structures and Properties

Maltose vs. cellobiose structure

Maltose and cellobiose are both composed of two glucose units linked by a $(1\rightarrow4)$ glycosidic bond, but they differ in stereochemistry at the glycosidic linkage. That single difference has major consequences for digestibility and biological function.

• Maltose: two $\alpha$-D-glucose units connected by an $\alpha(1\rightarrow4)$ glycosidic bond. It's found in malt and germinating cereal grains, and human $\alpha$-amylase can cleave this linkage.
• Cellobiose: two $\beta$-D-glucose units connected by a $\beta(1\rightarrow4)$ glycosidic bond. It's the repeating disaccharide unit of cellulose. Humans lack the enzyme (cellulase) needed to break this bond, which is why we can't digest cellulose.

The key structural point: in maltose, the anomeric carbon of the non-reducing glucose is in the $\alpha$ configuration. In cellobiose, it's in the $\beta$ configuration. This $\alpha$ vs. $\beta$ distinction at the glycosidic bond is what separates a digestible sugar from an indigestible one.

Reducing properties: Both maltose and cellobiose are reducing sugars. In each disaccharide, only one anomeric carbon is locked in the glycosidic bond (C1 of the non-reducing end). The other glucose unit (the reducing end) retains a free hemiacetal at C1, which can open to expose a free aldehyde group. That free aldehyde is what reacts with Fehling's or Benedict's reagent.

The anomeric carbon at the reducing end can also undergo mutarotation in solution, interconverting between $\alpha$ and $\beta$ anomers through the open-chain form.

Composition of lactose

Lactose is the primary sugar in mammalian milk. It's a disaccharide of $\beta$-D-galactose and D-glucose, connected by a $\beta(1\rightarrow4)$ glycosidic bond. The galactose supplies the anomeric carbon involved in the linkage, making it the non-reducing end.

Galactose is the C-4 epimer of glucose, meaning the two sugars differ only in the configuration of the hydroxyl group at C-4. Despite this small structural change, the body needs a specific enzyme (lactase, or $\beta$-galactosidase) to hydrolyze lactose. People who produce insufficient lactase experience lactose intolerance.

Like maltose and cellobiose, lactose shares a $(1\rightarrow4)$ glycosidic linkage. The difference is in monosaccharide composition: galactose + glucose rather than glucose + glucose.

Lactose is a reducing sugar because the glucose unit at the reducing end has a free hemiacetal at C1. It gives a positive test with Fehling's or Benedict's reagent.

Properties of sucrose

Sucrose is the common table sugar, composed of $\alpha$-D-glucopyranose and $\beta$-D-fructofuranose. What makes sucrose unique among the four disaccharides here is its glycosidic bond: an $\alpha(1\rightarrow2)\beta$ linkage connecting C1 of glucose directly to C2 of fructose.

This matters because C1 is the anomeric carbon of glucose and C2 is the anomeric carbon of fructose (fructose is a ketose, so its anomeric carbon is C2, not C1). Since both anomeric carbons are locked into the glycosidic bond, neither monosaccharide unit can ring-open to expose a free aldehyde or ketone.

The result: sucrose is a non-reducing sugar. It gives a negative test with Benedict's and Fehling's reagents, and it cannot undergo mutarotation.

Hydrolysis and invert sugar:

Acid-catalyzed or enzymatic (invertase/sucrase) hydrolysis of sucrose yields equimolar amounts of glucose and fructose. This mixture is called invert sugar because the optical rotation changes sign during the reaction:

1. Sucrose in solution is dextrorotatory ($[\alpha]_D = +66.5°$).
2. Upon hydrolysis, the mixture of glucose ($[\alpha]_D = +52.7°$) and fructose ($[\alpha]_D = -92°$) has a net levorotatory rotation.
3. The "inversion" of rotation from (+) to (−) gives invert sugar its name.

Invert sugar is sweeter than sucrose and is widely used in confectionery and syrups because it also resists crystallization.