MCAT Biochemistry Review

Chapter 4: Carbohydrate Structure and Function

4.2 Cyclic Sugar Molecules

Monosaccharides contain both a hydroxyl group, which can serve as a nucleophile, and a carbonyl group, which is the most common electrophile on the MCAT. Therefore, they can undergo intramolecular reactions to form cyclic hemiacetals (from aldoses) and hemiketals (from ketoses). Due to ring strain, the only cyclic molecules that are stable in solution are six-membered pyranose rings or five-membered furanose rings. In fact, such sugars tend to exist predominantly in cyclic form. The hydroxyl group acts as the nucleophile during ring formation, so oxygen becomes a member of the ring structure. Regardless of whether hemiacetal or hemiketal is formed, the carbonyl carbon becomes chiral in this process, and is referred to as the anomeric carbon. Figure 4.9 demonstrates how the carbonyl containing C-1 and the hydroxyl group on C-5 of D-glucose undergo intramolecular hemiacetal formation. One of two ring forms can emerge during cyclization of a sugar molecule: α or β. Because these two molecules differ at the anomeric carbon, they are termed anomers of one another. In glucose, the α-anomer has the –OH group of C-1 trans to the –CH2OH substituent (axial and down), whereas the β-anomer has the –OH group of C-1 cis to the –CH2OH substituent (equatorial and up).

Figure 4.9. Cyclic Sugar Formation via Intramolecular Nucleophilic Acyl Substitution Glucose forms a six-membered ring with two anomeric forms: α (left) and β (right).

HEXOSE CONFORMATIONS

Note how Figure 4.9 above has two kinds of projections for glucopyranose: the Haworth projection and the Fischer projection. The Haworth projection is a useful method for describing the three-dimensional conformations of cyclic structures. Haworth projections depict cyclic sugars as planar five- or six-membered rings with the top and bottom faces of the ring nearly perpendicular to the page. In reality the five-membered rings are very close to planar, but the pyranose rings adopt a chair-like configuration, and the substituents assume axial or equatorial positions to minimize steric hindrance. When we convert the monosaccharide from its straight-chain Fischer projection to the Haworth projection, any group on the right in the Fischer projection will point down.

MUTAROTATION

Exposing hemiacetal rings to water will cause them to spontaneously cycle between the open and closed form. Because the substituents on the single bond between C-1 and C-2 can rotate freely, either the α- or β-anomer can be formed, as demonstrated in Figure 4.10. This spontaneous change of configuration about C-1 is known as mutarotation, and occurs more rapidly when the reaction is catalyzed with an acid or base. Mutarotation results in a mixture that contains both α- and β-anomers at equilibrium concentrations (for glucose: 36% α, 64% β). The α-anomeric configuration is less favored because the hydroxyl group of the anomeric carbon is axial, adding to the steric strain of the molecule.

Figure 4.10. Mutarotation Interconversion between the α- and β-anomers via ring opening and reclosing.

MCAT Concept Check 4.2:

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

1.    Draw the less stable anomer of D-glucose in Haworth projection form.

2.    Draw the less stable anomer of D-glucose in chair configuration.