Carbohydrates

Carbohydrates are polyhydroxy aldehydes or ketones. For the MCAT you need to read Fischer and Haworth projections, assign D/L and identify anomers/epimers, explain mutarotation and tautomerism, and connect polysaccharide structure to function.

Priority labels: Must know = cold; Know the logic = mechanism not names; Passage-level = recognize, don't memorize; Optional = skippable.

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Classification and Nomenclature of Monosaccharides

What a Monosaccharide Is

Must know

A monosaccharide is a single polyhydroxy aldehyde or ketone that cannot be hydrolyzed into smaller sugar units. All share the empirical formula $\ce{(CH2O)_n}$, $n \geq 3$.

Two classification axes:

• By carbonyl: aldoses have an aldehyde ($\ce{-CHO}$) at C1; ketoses have a ketone, almost always at C2.
• By chain length: triose (3C), tetrose (4C), pentose (5C), hexose (6C).

Combine as prefixes: glucose is an aldohexose, fructose a ketohexose, ribose an aldopentose.

High-Yield Monosaccharides to Know by Name

Must know

Know the names, roles, and how they differ structurally.

Sugar	Type	Key Role
D-Glucose	aldohexose	primary fuel; blood sugar
D-Fructose	ketohexose	fruit sugar; in sucrose
D-Galactose	aldohexose	C4 epimer of glucose; in lactose
D-Mannose	aldohexose	C2 epimer of glucose
D-Ribose	aldopentose	RNA backbone
2-Deoxy-D-ribose	aldopentose	DNA (C2 $\ce{-OH}$ replaced by $\ce{-H}$)

Quick check: Fructose is a ketose. Which carbon bears its carbonyl? — C2.

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Absolute Configuration: D/L and R/S

The D/L System

Must know

The reference molecule is glyceraldehyde. Assign D or L from the highest-numbered chiral carbon (closest to the $\ce{-CH2OH}$ tail) in a Fischer projection:

• $\ce{-OH}$ on the right → D sugar
• $\ce{-OH}$ on the left → L sugar

Nearly all biological sugars are D; enzymes are stereospecific, so L-sugars are not used as metabolic substrates.

Fischer Projections

Know the logic

A Fischer projection is a 2D representation: carbon chain vertical with the carbonyl at the top; horizontal bonds point toward you, vertical bonds point away.

Counting stereoisomers: a sugar with $n$ chiral centers has at most $2^n$ stereoisomers. An aldohexose has 4 chiral centers (C2–C5) → $2^4 = 16$ stereoisomers (8 D + 8 L). You do not need to assign R/S at every center or memorize the full aldose family tree.

R/S at the Anomeric Carbon

Passage-level

The anomeric carbon (C1 in aldoses, C2 in ketoses) is the new chiral center formed on cyclization. The key point: $\alpha$ and $\beta$ are anomers (a type of diastereomer); you won't be asked to assign R/S here.

Quick check: D-Galactose has its $\ce{-OH}$ at C5 projecting to the right in a Fischer projection. True or false? — True. All D-hexoses have $\ce{-OH}$ on the right at C5; that's the definition of D.

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Cyclic Structures and Conformations of Hexoses

Why Sugars Cyclize

Must know

Open-chain sugars equilibrate with ring forms: the electrophilic carbonyl carbon is attacked intramolecularly by a distant hydroxyl oxygen, forming a hemiacetal (aldose) or hemiketal (ketose).

$\ce{R-CHO + HO-R' <=> R-CH(OH)-O-R'}$

For glucose, the C5 $\ce{-OH}$ attacks C1 to form a six-membered pyranose ring. Fructose forms either a pyranose or a five-membered furanose (C4 $\ce{-OH}$ attacks C2).

Ring	Name	Example
5-membered	Furanose	Fructose (in sucrose), Ribose
6-membered	Pyranose	Glucose, Galactose

The Anomeric Carbon and $\alpha$/$\beta$

Must know

When the ring closes, the former carbonyl carbon becomes the new anomeric carbon, giving two anomers:

• $\alpha$ anomer: anomeric $\ce{-OH}$ axial in the chair; points down in a Haworth projection.
• $\beta$ anomer: anomeric $\ce{-OH}$ equatorial; points up in a Haworth.

Know the logic

Haworth shortcut for D-hexoses: right in Fischer = down in Haworth; left = up. The $\ce{-CH2OH}$ (C6) goes up for D-sugars.

Chair Conformations and Stability

Must know

The real shape of a pyranose is a chair, with substituents axial or equatorial; equatorial is favored (less steric strain). $\beta$-D-glucose is the most stable sugar because all its substituents are equatorial — part of why glucose is the preferred fuel. $\alpha$-D-glucose has the anomeric $\ce{-OH}$ axial, so it is slightly less stable; at equilibrium (mutarotation) the mix is roughly 64% $\beta$, 36% $\alpha$.

Worked example: Pure $\alpha$-D-glucose dissolved in water reads $[\alpha]_D = +112°$, then drifts to $+52.7°$. Why?

The ring opens and re-closes as $\alpha$ or $\beta$ ($[\alpha]_D = +18.7°$). The equilibrium mixture ($\approx 36\% \alpha + 64\% \beta$) gives a weighted average:

$[\alpha]_{eq} = (0.36)(+112°) + (0.64)(+18.7°) \approx +52.3°$

This is mutarotation — interconversion of anomers via the open chain. The final value lies between the two pure-anomer values, as expected for a mixture.

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Epimers and Anomers

Epimers

Must know

Epimers differ at exactly one chiral center (other than the anomeric carbon):

• C4 epimers: D-Glucose and D-Galactose (basis of galactosemia).
• C2 epimers: D-Glucose and D-Mannose.

"Epimer" always implies a specific center — glucose and galactose are C4 epimers.

Anomers

Must know

Anomers are the special case that differ only at the anomeric carbon. $\alpha$- and $\beta$-D-glucose are anomers; they interconvert via the open chain (mutarotation).

Quick check: Are $\alpha$-D-glucose and $\alpha$-D-galactose anomers? — No. They differ at C4, so they are C4 epimers, not anomers.

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Hydrolysis of the Glycoside Linkage

How Glycosidic Bonds Form

Must know

When the anomeric $\ce{-OH}$ of one sugar reacts with the $\ce{-OH}$ of another molecule, water is lost and an O-glycosidic bond forms. The anomeric carbon is now an acetal (from aldose) or ketal (from ketose) — stable, and unable to open. So once a glycoside forms, the sugar loses its free anomeric carbon and is no longer a reducing sugar.

A reducing sugar has a free anomeric $\ce{-OH}$ that can open to the aldehyde/ketone and be oxidized. All monosaccharides, maltose, and lactose are reducing; sucrose is not.

Hydrolysis

Must know

Hydrolysis reverses glycoside formation — water attacks the acetal carbon (acid- or enzyme-catalyzed):

$\ce{Glycoside + H2O ->[\text{H}^+ \text{ or enzyme}] Monosaccharide + R-OH}$

Enzymes are specific: $\alpha$-glycosidases cleave $\alpha$ links, $\beta$-glycosidases (e.g., lactase) cleave $\beta$ links. Lactose intolerance = insufficient lactase for the $\beta(1\to4)$ bond.

Reducing Sugar Tests

Know the logic

Both detect a free (open-chain) reducing sugar:

• Benedict's: $\ce{Cu^2+}$ (blue) → $\ce{Cu2O}$ (brick-red precipitate).
• Tollens': $\ce{Ag+}$ → $\ce{Ag^0}$ (silver mirror).

Quick check: Benedict's test on sucrose — what do you observe? — No color change (stays blue). Sucrose is non-reducing: both anomeric carbons are in the glycosidic bond.

N-Glycosidic Bonds

Passage-level

The anomeric carbon can bond to nitrogen instead of oxygen. Two examples: the sugar–base bond in every nucleoside/nucleotide, and sugars attached to asparagine in N-linked glycoproteins. Like O-glycosides, these lock the anomeric carbon (non-reducing).

Oxidation and Reduction Products

Know the logic

Named products:

• Aldonic acid — oxidation of the C1 aldehyde to $\ce{-COOH}$ (e.g., glucose → gluconic acid; what Tollens'/Benedict's do).
• Uronic acid — oxidation of the terminal C6 $\ce{-CH2OH}$ to $\ce{-COOH}$ (e.g., glucuronic acid).
• Alditol — reduction of the carbonyl to a polyol (e.g., glucose → sorbitol).

Phosphorylation of Sugar Hydroxyls

Passage-level

Sugar $\ce{-OH}$ groups are ordinary alcohols. Biologically the key reaction is phosphorylation by kinases, giving sugar phosphates (e.g., glucose-6-phosphate). The charged phosphate traps the sugar in the cell and activates it for metabolism.

Amino Sugars and Deoxy Sugars

Passage-level

Amino sugars replace a ring $\ce{-OH}$ with an amino group, often N-acetylated — e.g., N-acetylglucosamine (GlcNAc) (building block of chitin). Deoxy sugars lack one $\ce{-OH}$ — key example 2-deoxyribose in DNA.

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Keto-Enol Tautomerism of Monosaccharides

The Concept

Know the logic

Tautomers interconvert by proton transfer. The relevant pair is the keto form ($\ce{C=O}$) and the enol form ($\ce{-OH}$ on a $\ce{C=C}$). Keto is usually favored, but the enol is briefly accessible.

$\ce{R-CO-CH2-R' <=> R-C(OH)=CH-R'}$

Why It Matters

Know the logic

Aldoses and ketoses interconvert via an enediol intermediate. In glycolysis, phosphoglucose isomerase converts glucose-6-phosphate (aldose) to fructose-6-phosphate (ketose) through an enediol at C1–C2. The same enolization lets glucose, fructose, and mannose interconvert in base (no need to name the reaction). It also explains why ring-form reducing sugars can be oxidized — the equilibrium pulls rings open via the enolizable open chain.

Quick check: Phosphoglucose isomerase converts an aldose to a ketose without breaking the carbon skeleton. What intermediate does it proceed through? — An enediol intermediate at C1–C2.

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Disaccharides

Formation and Naming

Must know

Disaccharides are two monosaccharides joined by an O-glycosidic bond, named (anomeric carbon) $\to$ (carbon of second sugar) with $\alpha$/$\beta$. Know all four:

Disaccharide	Components	Linkage	Reducing?	Role
Maltose	Glc + Glc	$\alpha(1\to4)$	Yes	starch digest product
Lactose	Gal + Glc	$\beta(1\to4)$	Yes	milk sugar
Sucrose	Glc + Fru	$\alpha(1\to2)\beta$	No	table sugar
Trehalose	Glc + Glc	$\alpha(1\to1)\alpha$	No	insect/fungal storage

Sucrose is the most-tested non-reducing disaccharide: both anomeric carbons are locked, so neither can open. Hydrolysis by sucrase (invertase) gives an equimolar glucose + fructose invert sugar. Lactose and maltose each keep a free anomeric carbon → reducing.

Quick check: A patient lacks sucrase. After eating table sugar, what accumulates in the intestinal lumen? — Sucrose itself, causing osmotic diarrhea and bloating from bacterial fermentation.

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Polysaccharides

Starch

Must know

Starch is the plant storage polysaccharide, with two parts:

• Amylose: linear $\alpha(1\to4)$ glucose; the $\alpha$ links coil it into a helix that binds iodine ($\ce{I3^-}$) → blue-black (starch test).
• Amylopectin: like amylose plus $\alpha(1\to6)$ branch points (~every 24–30 units); branching gives more non-reducing ends for faster hydrolysis.

Digestion: salivary then pancreatic $\alpha$-amylase cleave $\alpha(1\to4)$; a debranching enzyme handles $\alpha(1\to6)$.

Glycogen

Must know

Glycogen is the animal analog of amylopectin but more highly branched ($\alpha(1\to6)$ every 8–12 units), giving many non-reducing ends for rapid mobilization by glycogen phosphorylase. Stored in liver (blood glucose) and muscle (local energy).

Optional

Enzymes: glycogen synthase builds $\alpha(1\to4)$ (from UDP-glucose); branching enzyme makes $\alpha(1\to6)$; phosphorylase cleaves terminal $\alpha(1\to4)$ by phosphorolysis; debranching enzyme cleaves $\alpha(1\to6)$.

Cellulose

Must know

Cellulose is $\beta(1\to4)$ glucose. The $\beta$ links extend the chain into straight ribbons that hydrogen-bond into rigid, insoluble microfibrils (plant cell walls). Humans lack cellulase, so cellulose is indigestible fiber; ruminants digest it via gut microbiota.

Chitin

Passage-level

Chitin is like cellulose but built from $\beta(1\to4)$-linked N-acetylglucosamine; it forms arthropod exoskeletons and fungal cell walls.

Quick check: Why does $\alpha(1\to4)$ in starch coil while $\beta(1\to4)$ in cellulose extends? — In $\alpha$, the anomeric $\ce{-OH}$ is axial, tilting each unit → helix. In $\beta$, it's equatorial; alternating $180°$ flips give a flat, linear chain that H-bonds laterally for rigidity.

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Common Confusions & Tricks

1. $\alpha$ vs. $\beta$. Haworth (D-sugars): $\alpha$ = anomeric $\ce{-OH}$ down. Chair: $\alpha$ = axial. $\alpha$-D-glucose: axial → less stable → 36%; $\beta$ = equatorial → 64%.

2. Epimer ≠ Anomer. An anomer is a specific epimer (differs only at the anomeric carbon). C4 epimers (glucose/galactose) are NOT anomers.

3. Sucrose is the only common non-reducing disaccharide — and the one most likely tested. Both anomeric carbons are bonded ($\alpha(1\to2)\beta$).

4. D-Fructose cyclizes at C2, not C1. As a ketose, its anomeric carbon is C2; $\alpha$/$\beta$ still applies there.

5. Glycogen is more branched than amylopectin — every 8–12 vs. 24–30 glucoses → faster mobilization.

6. Cellulose is $\beta(1\to4)$, not $\alpha(1\to4)$. That single change makes a nutrient into indigestible fiber.

7. The iodine test is specific to amylose. Glycogen gives reddish-brown; cellulose, no color.

8. Fischer D/L: look only at the bottom-most (highest-numbered) chiral center. Right = D, Left = L.

9. Benedict's → reducing sugar → free anomeric carbon. Monosaccharides, maltose, lactose are reducing; sucrose and trehalose are not.

10. Mutarotation requires water and goes through the open chain. In dry conditions anomers can't interconvert; a freshly dissolved solution holds the anomer you dissolved until equilibrium.

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Key Equations

Expression	Variables & Use
$\ce{(CH2O)_n}$	Empirical formula of monosaccharides; $n =$ number of carbons.
$[\alpha]_{eq} = \chi_\alpha [\alpha]_\alpha + \chi_\beta [\alpha]_\beta$	Weighted-average optical rotation at equilibrium (mutarotation); $\chi$ = mole fraction.
$\ce{R-CHO + HO-R' <=> R-CH(OH)-O-R'}$	Hemiacetal formation; reversible ring-closure step.
$\ce{Hemiacetal + HO-R'' ->[\text{H}^+] Acetal + H2O}$	Glycoside (acetal) formation; removes free anomeric $\ce{-OH}$; product non-reducing.
$\ce{Glycoside + H2O ->[\text{H}^+ \text{ or enzyme}] Sugar_1 + Sugar_2}$	Hydrolysis of O-glycosidic bond; regenerates free anomeric $\ce{-OH}$.
$\ce{R-CO-CH2R' <=> R-C(OH)=CHR'}$	Keto-enol tautomerism; basis of aldose-ketose interconversion via enediol.
$\ce{2 Cu^2+ + R-CHO + 2 OH- -> Cu2O v + R-COOH}$	Benedict's test; $\ce{Cu^2+}$ (blue) → $\ce{Cu2O}$ (red); positive = reducing sugar.