11.1 Carbohydrates: Structure & Nomenclature

Classifying Monosaccharides

Carbohydrates are polyhydroxy aldehydes or ketones, or compounds that hydrolyze to them. The simplest carbohydrates, monosaccharides, are classified two ways at once: by carbonyl type and by chain length.

• An aldose has a terminal aldehyde (–CHO) carbonyl; a ketose has an internal ketone carbonyl (almost always at C2).
• A three-carbon sugar is a triose, four carbons a tetrose, five a pentose, six a hexose.

Combine the two systems and you get the common names the MCAT expects you to recognize on sight: glucose is an aldohexose, fructose is a ketohexose, ribose is an aldopentose, and deoxyribose (missing the C2 hydroxyl) is the aldopentose found in DNA's backbone. Galactose and mannose are also aldohexoses you should be able to draw from memory.

Absolute Configuration: D and L

Absolute configuration in sugars is assigned from the Fischer projection: draw the carbon chain vertically with the most oxidized carbon (the carbonyl, C1 in an aldose) at the top, then look at the chiral carbon farthest from the carbonyl — C5 in a hexose. If the hydroxyl on that carbon points right, the sugar is D; if it points left, it is L. Nearly every sugar made and used in human metabolism is the D-enantiomer — a biological convention, not a thermodynamic necessity. You should recognize D-glucose from its Fischer projection: reading C2 through C5, the hydroxyls point right, left, right, right.

Don't confuse the D/L label with the R/S system. R/S independently assigns configuration to every stereocenter using priority rules; D/L is a single descriptor based on only the reference carbon farthest from the carbonyl. A sugar's complete stereochemical identity requires specifying every stereocenter, but its D/L name comes from just that one.

Cyclic Structure and Conformations of Hexoses

In aqueous solution, an aldohexose does not stay open-chain. The C5 hydroxyl attacks the C1 aldehyde carbon intramolecularly, forming a cyclic hemiacetal — a six-membered ring called a pyranose (five carbons plus one ring oxygen). A five-membered ring is a furanose; ketoses commonly form furanoses when the C5 hydroxyl attacks the C2 ketone. Glucose exists almost entirely (over 99%) as the pyranose form at equilibrium.

Cyclization creates a brand-new stereocenter at the former carbonyl carbon, called the anomeric carbon. Its two possible configurations are the α-anomer and β-anomer, together called anomers.

• Haworth projections draw the ring flat and viewed edge-on, with the anomeric carbon on the right and the ring oxygen at the back right. For a D-sugar, a substituent drawn pointing down in a Haworth projection corresponds to pointing right in the Fischer projection.
• α-D-glucopyranose has its C1 hydroxyl pointing down (trans to the C5 reference substituent); β-D-glucopyranose has it pointing up (cis to that substituent).
• Chair conformations give the more physically realistic 3-D picture. β-D-glucopyranose is the single most stable hexose conformation possible: every substituent — all four hydroxyls and the CH2OH — sits equatorial, minimizing 1,3-diaxial strain. This low-strain chair is a favorite MCAT reasoning point for why glucose is biology's dominant sugar.

Because the open-chain and cyclic forms interconvert through the hemiacetal equilibrium, dissolving a single pure anomer of glucose produces a solution whose optical rotation slowly drifts to an equilibrium value as α- and β-anomers interconvert (with a small amount of open-chain aldehyde present at any instant). This phenomenon is called mutarotation.

Epimers vs. Anomers

An epimer pair consists of two diastereomers differing in configuration at exactly one stereocenter out of several. Glucose and galactose are C4 epimers; glucose and mannose are C2 epimers. An anomer pair is a restricted special case of epimers: the one differing stereocenter must specifically be the anomeric carbon (C1 in aldoses, C2 in ketoses). All anomers are epimers, but not all epimers are anomers — a distinction MCAT distractors exploit directly.

Hydrolysis of the Glycosidic Linkage

When the anomeric hydroxyl of a cyclic hemiacetal reacts with another alcohol — which may belong to a second sugar — water is lost and a full acetal forms. This C–O–C linkage is the glycosidic bond, and the product is a glycoside. Unlike a hemiacetal, a full acetal is configurationally locked: it cannot reopen to the free carbonyl under basic or neutral conditions, so a sugar tied up in a glycosidic bond no longer mutarotates and can no longer act as a reducing sugar through that carbon.

Glycosides are stable to base but cleaved by acid-catalyzed hydrolysis: aqueous acid protonates the ring oxygen, the C1–O bond breaks to expel the other sugar (or aglycone) and generate a resonance-stabilized oxocarbenium ion, and water adds back to regenerate the hemiacetal. This reaction — essentially the reverse of acid-catalyzed glycoside formation — is exactly how digestive glycosidase enzymes and stomach acid break starch and disaccharides down into free monosaccharides.

Keto-Enol Tautomerism of Monosaccharides

Under basic conditions, the carbon alpha to a sugar's carbonyl (C2 in an aldose) can be deprotonated and reprotonated through a shared enediol intermediate, interconverting keto and enol forms. Because the enediol is symmetric with respect to which carbon ends up bearing the carbonyl, base treatment slowly interconverts glucose, fructose, and mannose through that common enediol — the Lobry de Bruyn–Van Ekenstein transformation. This is why fructose, despite being a ketone, still gives a positive Tollens' test and Benedict's test (both classic reducing-sugar assays): under the mildly basic test conditions, some fructose tautomerizes to a glucose/mannose-type enediol bearing a free aldehyde, which is then oxidized.

Disaccharides and Polysaccharides

Two monosaccharides joined by a glycosidic bond form a disaccharide. Know these three cold:

Sucrose is non-reducing because both anomeric carbons are tied up in the glycosidic bond, leaving no free hemiacetal to open to an aldehyde.

Polysaccharides are long monosaccharide chains. Starch, the plant storage form, has two components: amylose (unbranched, α(1→4) links, coils into a helix) and amylopectin (branched, α(1→4) with α(1→6) branch points roughly every 24–30 residues). Glycogen, the animal storage analog of amylopectin, is far more heavily branched (roughly every 8–12 residues), maximizing the number of chain ends enzymes can act on simultaneously for rapid glucose mobilization. Cellulose, by contrast, is a structural polysaccharide of glucose linked by β(1→4) bonds; this single stereochemical change from starch's α-linkage produces long, flat, hydrogen-bonded fibers instead of a helix. Humans lack β-glycosidase enzymes, so we cannot digest cellulose for calories even though it is chemically "just glucose."