Chapter 7: Carbohydrates and Glycobiology

What are carbohydrates primarily composed of?

Carbon, hydrogen, and oxygen in roughly a (CH₂O)_n formula.

What are the three major classes of carbohydrates?

Monosaccharides, oligosaccharides, polysaccharides.

What determines carbohydrate stereochemistry?

The orientation of hydroxyl groups around asymmetric carbons.

What type of sugars are most biologically relevant: D or L?

D-sugars.

Which carbon determines D vs L configuration?

The chiral carbon farthest from the carbonyl carbon.

What is an epimer?

Sugars that differ at one chiral center. Example: Glucose vs Mannose.

What is the difference between aldoses and ketoses?

Aldoses have an aldehyde at C1; ketoses have a ketone at C2.

Structure characteristics of D-Glucose?

Six-carbon aldohexose; OH pattern: Right, Left, Right, Right on C2–C5.

What ring forms does glucose make?

α-D-glucopyranose and β-D-glucopyranose.

Which anomer of glucose has OH pointing down at anomeric carbon?

α-D-glucopyranose.

Which anomer has OH up?

β-D-glucopyranose.

How does D-galactose differ from glucose?

Epimer at carbon 4. OH on C4 is left instead of right.

How does D-mannose differ from glucose?

Epimer at carbon 2 (OH on C2 is left).

What type of sugar is fructose?

A ketohexose with carbonyl at C2.

What ring structures does fructose form?

β-D-fructofuranose and α-/β-D-fructopyranose.

What type of sugar is ribose?

An aldopentose (5-carbon sugar).

What is ribose mainly used for?

RNA backbone, ATP, NAD⁺/NADP⁺, coenzymes.

What is the Fischer projection OH pattern of D-ribose?

OH on C2, C3, C4 all on the RIGHT.

What ring form does ribose commonly adopt in RNA?

β-D-ribofuranose (5-membered ring).

What makes ribose chemically reactive?

More open-chain form present → more reactive than deoxyribose.

What is galactosamine?

What is galactosamine?

What is mannosamine?

Mannose where C2 OH → NH₂.

What carbon always contains amino modification in amino sugars?

Carbon 2

Why are sugars called “reducing”?

Their aldehyde can reduce Cu²⁺ → Cu⁺ (Fehling’s) or Ag⁺ → Ag (Tollens).

What form must sugars adopt to reduce metals?

Open-chain aldehyde form.

What is mutarotation?

Interconversion between α and β anomers via open-chain form.

What determines if a disaccharide is reducing?

If the anomeric carbon is free (not in glycosidic bond).

In glycosidic bond notation (e.g., α1→4), what does each number indicate?

Position of anomeric carbon and the carbon it bonds to.

What must you always specify when naming glycosidic bonds?

Whether it is α or β.

What monomers make cellulose?

β-D-glucose units.

Type of linkage in cellulose?

β(1→4)

Why is cellulose insoluble?

Extensive inter- and intramolecular hydrogen bonding creates rigid fibers.

Why can’t humans digest cellulose?

We lack cellulase.

What is chitin composed of?

N-acetylglucosamine units.

Linkage in chitin?

β(1→4).

Why is chitin slightly weaker than cellulose?

N-acetyl group disrupts symmetry → fewer H-bonds.

What are dextrans?

Polymers of glucose varying in linkage (α1→6, α1→2, α1→3).

Why are dextrans structurally variable?

Rotation around phi/psi of different linkages.

What are dextrans made up of?

Produced by the hydrolysis of starch or glycogen. The smaller versions of those sugers can be linked to form dextrans

What is starch?

A mixture of two homopolysaccharides of glucose, Amylose and amylopectin. Serves as the main storage form of glucose in plants.

Difference between Amylose and Amylopectin

Amylose is unbranched with a1→4 linked residues, while amylopectin form branches with a1→6 linkers every 24-30 residues.

What degrades and debranches starch? Where are they located?

Amylases and a-glucosidases. They are located in granules that store starch.

Why does amylose form a helix?

α(1→4) linkages naturally bend chain.

What are hyaluronan monomers

D-glucuronic acid + N-acetyl-D-glucosamine (β1→3, β1→4)

Function of hyaluronan?

Lubrication, hydration, shock absorption in ECM

Charge properties of heparin?

Highly negatively charged

What does heparin do?

Activates antithrombin → prevents blood clotting.

What portion is sugar vs protein in glycoproteins?

Small carbohydrate, large protein.

O-linked glycoprotein attachment site?

Ser/Thr OH

N-linked glycoprotein attachment site?

Asn (via NH₂)

What do glycoproteins help with?

Protein identity, recognition, signaling.

What is a glycolipid? Where are they found?

A lipid with a covalently bound oligosaccharide. They are found plant and animal cell membranes and are important for protein-protein interactions.

Significance of Glycolipids

Sugars coming off of blood cells helps determine blood groups. It also covers the peptidoglycan layer of bacteria. 

What are Proteoglycans? What makes them negatively charged?

Negatively charged glycoaminoglycans that are attached to a large rod-shape protein in the cell membrane. The negative charges of the sulfates and carboxylic acids (uronic acid) make them negatively charged.

Relative sugar/protein ratio of Proteoglycans?

Large carbohydrate, small protein. Opposite of glycoproteins.

Syndecan anchor type?

Single transmembrane domain.

Single transmembrane domain.

Glypican anchor type?

What are proteoglycan aggregates?

Supramolecule assemblies of many core proteins bound to a single molecule of hyaluronan.

Major function of proteoglycan aggregates

Water retention + lubrication in ECM

Major ECM components? (Exracellular matrix)

Proteoglycans, collagen, elastin

What breaks ECM during tumor invasion?

Heparinase

What are lectins?

Proteins that bind carbohydrates specifically via hydrogen bonding + hydrophobic interactions.

What do lectins bind on sugars?

Polar side→H-bonding; nonpolar side→hydrophobic interactions.

Role of lectins in infection?

Viruses/bacteria invade by binding host cell carbohydrates via lectins.

What determines ABO blood type?

Oligosaccharides on glycoproteins & glycolipids.

Type A blood:

A antigen; anti-B antibodies.

Type B blood:

B antigen; anti-A antibodies.

Type AB blood:

A + B antigens; no antibodies.

Type O blood:

A/B antigens; both antibodies present

What does methyl iodide do?

Methylates free OH groups; cannot methylate glycosidic OH.

Why methylation analysis?

Identifies which OHs were free → reveals linkage patterns.

What does acid hydrolysis do?

Breaks polysaccharides into monosaccharides.

What technique visualizes glycan binding?

Fluorescence labeling of proteins binding sugars.

What determines the bending (“chair/boat”) preferences of sugar rings?

Steric hindrance + minimizing eclipsing interactions.

Why do sugars prefer the cyclic form over open-chain?

Cyclic form is more stable due to intramolecular hemiacetal/hemiketal formation.

What is the anomeric carbon?

Carbonyl carbon that becomes chiral upon ring closure.

Carbonyl carbon that becomes chiral upon ring closure.

It has a hemiacetal/hemiketal OH that can open/close, enabling mutarotation.

Which sugars do NOT count as reducing?

Sugars whose anomeric carbon is locked in a glycosidic bond (e.g., sucrose).

What chemical test identifies reducing sugars?

Fehling’s (Cu²⁺ → Cu⁺) and Tollens (Ag⁺ → Ag°).

What is oxidized and what is reduced in these tests for reducing sugars?

Sugar aldehyde oxidized → Cu²⁺/Ag⁺ reduced.

What functional groups can replace OH groups in sugars?

Amino, N-acetyl, phosphate, methyl, sulfate.

What position is phosphorylated in glucose-6-phosphate?

Carbon 6

What is an amino sugar?

Sugar where OH on C2 → NH₂ (e.g., glucosamine).

What are sugar acids?

Sugars oxidized at C1 or C6 (e.g., glucuronic acid).

How do you identify α vs β in glycosidic bonds?

Orientation of OH on anomeric carbon relative to CH₂OH group.

What defines a β(1→4) linkage?

Anomeric carbon in β orientation connecting to C4 of another sugar.

What defines an α(1→6) linkage?

Anomeric C1 (α) attaches to C6 hydroxyl of another sugar.

Why does amylopectin branch?

Branching increases solubility and metabolic accessibility.

Why can humans digest starch but not cellulose?

We have enzymes for α(1→4) but not β(1→4).

Why is cellulose more rigid than starch?

β(1→4) linkages form straight, extended fibers stabilized by H-bonds.

What modification distinguishes chitin from cellulose?

N-acetyl group on C2 of each glucose.

Why does chitin form exoskeletons?

Flexible, strong, but lightweight; extensive H-bonding.

Why isn’t Chitin as strong as Cellulose?

The N-acetyl group on the C2 carbon disrupts the symmetry of the moleculeand doesn’t fit as well. It can use as many hydrogen bonds

Dextran (and all sugars really) linkages allow what structural feature?

Unlimited phi/psi rotation (Ramachandran-like freedom) due to the lack of double bonds.

Why do Glycosaminoglycans attract water?

Negative charge causes strong hydration shell.

What is special about hyaluronan compared to other GAGs?

Not sulfated; extremely long polymer chain.

Physiological role of Glycosaminoglycans?

Lubrication of the joints, cushioning and holding together connective tissue, and forms a meshwork with firous proteins to form ECM structure.

Why does hyaluronan form gel-like matrix?

Massive hydration and extended structure.

What does hyaluronan do in joints?

Acts as lubricant and shock absorber.

Heparin composition?

Repeating sulfated sugars (high charge density).