Topic 6: Carbohydrates: Structure, Function, and Biological Significance

Why Study Carbohydrates?

- Most abundant biomolecules on Earth

- Major global carbon reservoir

What are carbohydrates central to?

- Energy metabolism

- Structural biology

- Cell recognition

- Extracellular matrix organization

Photosynthesis and Carbon Fixation

- Atmospheric CO₂ converted into carbohydrates

- Catalyzed by: Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO)

- Occurs in chloroplasts

RuBisCO

- Most abundant enzyme on Earth

~50% of total chloroplast protein

Carbohydrates in the Biosphere

- Plants, cyanobacteria, algae synthesize carbohydrates

Non-photosynthetic organisms

Depend on carbohydrates as carbon and energy source

Energy flow through ecosystems depends on what?

carbohydrate synthesis

Primary energy source for most organisms

Glucose, Glycogen, Starch

Where do carnivores obtain significant energy from?

proteins

Structural Functions of Peptidoglycan

Bacterial cell wall

Structural Functions of cellulose

Plant cell wall

Structural Functions of Chitin

Arthropod exoskeleton

Structural Functions of Proteoglycans

Extracellular matrix

Structural Functions of Hyaluronic acid

Lubrication (joints, vitreous humor)

Chemical Definition of Carbohydrates

- Polyhydroxy aldehydes

- Polyhydroxy ketones

- Compounds yielding these upon hydrolysis

Chemical Definition of Carbohydrates- General formula

Often (CH₂O)n

Chemical Definition of Carbohydrates- May Contain

- Nitrogen

- Phosphate

- Sulfate groups

How are carbohydrates are classified?

According to the size of the molecule

Carbohydrate Classification by Size

1. Monosaccharides - simple sugars

2. Oligosaccharides - made up of two or a few monosaccharide units

3. Polysaccharides - made up of many monosaccharide units

Simple Carbohydrates

monosaccharides (glucose, fructose, galactose) and disaccharides (maltose, lactose, sucrose)

Complex carbohydrates

polysaccharides --> starches & fibres

Monosaccharides

- Simplest carbohydrates

- Cannot be hydrolyzed further

- Water soluble

- Sweet taste

- Unbranched carbon chains

Examples of monosachharides

Glucose, Mannose, Galactose, Fructose

Oligosaccharides

- Polymers of 2-20 monosaccharide units

- Monosaccharides linked by glycosidic bonds

- Oligosaccharides (≥3 units) are often attached to: Proteins → Glycoproteins OR Lipids → Glycolipids

How are oligosachharides named?

Named according to the number of units:

- 2 → Disaccharide

- 3 → Trisaccharide

- 4 → Tetrasaccharide

What carbohydrate are the most abundant?

Disaccharides

- Sucrose (cane sugar)

- Lactose (milk sugar)

Polysaccharides

- 20 monosaccharide units

- Linear or branched

- Storage or structural roles

Examples of polysachharides

- Starch

- Glycogen

- Cellulose

Monosaccharide Chemical Nature

- polyhydroxy aldehydes or ketones

- General formula: (CH₂O)n

- Polymeric carbohydrates yield these, upon hydrolysis

Monosaccharide Characteristics

- Water-soluble

- Crystalline solids

- Usually sweet

- Unbranched carbon chains

Monosaccharide Functional Groups

- Aldoses → contain an aldehyde group (-CHO)

- Ketoses → contain a ketone group (C=O)

- Remaining carbons carry hydroxyl (-OH) groups

Biologically Important Monosaccharide Examples

hexose, glucose, pentose

Hexoses

- most common monosaccharides

- Glucose → major metabolic fuel

- Fructose → fruit sugar

Glucose polymers

starch, glycogen, cellulose

Pentoses

- D-ribose → RNA

- 2-deoxy-D-ribose → DNA

Chirality in Monosaccharides

all, except dihydroxyacetone, have a C attached to 4 different groups

chiral (asymmetric) carbon

Carbon attached to four different groups

# stereoisomers vs. # chiral centers

n chiral centers → 2ⁿ stereoisomers

(1 chiral center → 2 stereoisomers)

enantiomers

Stereoisomers that are mirror images

Perspective Structure/ Wedge and Dash Structure

- C chain drawn vertically

- Highest-numbered carbon at bottom

- Vertical bonds → project away from viewer

- Horizontal bonds → project toward viewer

Fischer Projection

- 3D structure projected onto a flat plane

- Widely used for comparing sugar stereochemistry

Glyceraldehyde (The Reference Molecule)

- Smallest chiral monosaccharide

- Contains one asymmetric carbon

- Exists as: D-glyceraldehyde → OH on the right Or L-glyceraldehyde → OH on the left

D and L forms of glyceraldehyde

are mirror images

D/L Nomenclature in Higher Sugars

1. Number carbons normally (carbonyl carbon = C1 in aldoses)

2. Examine the highest-numbered chiral carbon

3. Compare its configuration to glyceraldehyde

4. Most naturally occurring sugars → D-configuration

Aldoses

- Polyhydroxy aldehydes

- Example: Aldohexoses -contain 4 asymmetric (chiral) Cs (therefore 2^4 = 16 stereoisomers with 8D & 8D)

- CHO group at top?

How are higher aldoses derived?

by sequential insertion of -CHOH groups adjacent to the aldehyde group, starting from glyceraldehyde.

Epimers

- Molecules that differ in configuration at only one chiral carbon Examples:

• D-Glucose & D-Mannose → C-2 epimers (where the C differs)

• D-Glucose & D-Galactose → C-4 epimers

What does small stereochemical change result in

major biochemical consequences

Ketoses

- Polyhydroxy ketones

- Carbonyl group located internally (usually C-2)

Naming Ketoses

Naming rule (4- and 5-C ketoses):

- Derived from corresponding aldose by inserting "ul"

Erythrose → Erythrulose; Ribose → Ribulose; Xylose → Xylulose

- exceptions: named by source (fructose -fruit sugar)

Cyclic Structures of Monosaccharides

In aqueous solution:

- Aldoses (≥4 carbons) and ketoses (≥5 carbons) predominantly exist in cyclic form

Why Sugars Form Rings

- Ring formation occurs via Intramolecular hemiacetal formation (aldoses) and intramolecular hemiketal formation (ketoses)

- Rxn bw carbonyl group (aldehyde/ketone) and internal hydroxyl group

Pyranose Structures (6-membered rings)

- cyclic carb molecules resemble pyran ring → called pyranoses

- 2 conformations: Chair (more stable) Boat

- Formation creates new chiral center at Anomeric carbon (C-1 in aldoses; C-2 in ketoses)

Chair conformation stability

- more stable than boat

- Bulky groups prefer equatorial positions

anomeric carbon

- initially not chiral carbon, but becomes one after taking cyclic form

- C in cyclic sugar that was the carbonyl C in linear form

(C-1 in aldoses; C-2 in ketoses)

anomers

- alpha-anomers: OH down

- beta-anomers: OH up

- type of stereoisomer in cyclic sugars that differ only in the configuration around the anomeric carbon

(C-1 in aldoses; C-2 in ketoses)

Anomers Examples

- α-D-glucopyranose

- β-D-glucopyranose

- Differ only at the anomeric carbo

Furanose Structures (5-membered rings)

- Resemble furan ring → called furanoses

- usually attack 2nd C

- Common in Fructose & Ribose

- Aldohexoses can form furanoses, but pyranoses are usually more stable

The same monosaccharide can either create what?

pyranoses and furanoses (more stable b/c can handle bulky groups)

- riboses (5C) like furanose form

Reversibility & Reducing Sugars

- Hemiacetal/hemiketal formation is reversible

- α and β forms exist in equilibrium in solution

- Rings can reopen → regenerate free aldehyde/ketone

- Therefore, monosaccharides can be oxidized

Benedicts test

1. Glucose reduces Cu²⁺ → Cu⁺

2. Forms brick red Cu₂O precipitate

3. Basis of reducing sugar tests (e.g., Benedict's test) - find out if sugas there in urine, normally glucose not there. then diabetic

- benedict solution contains Cu ions (blue), then green, orange, red.

Derivatives of monosaccharides

In addition to simple sugars, living organisms contains sugar derivatives in which OH groups are replaced by other groups

Glycosidic Bonds

- link oligosaccharide monomers by O-glycosidic bonds

- Formed when anomeric Cof one sugar reacts w hydroxyl of another sugar. Water is eliminated (condensation rxn)

Reducing Sugar and disaccharide with 2 glucose residues

The first glucose:

- Its anomeric C is involved in glycosidic bond. Therefore, it's not free, so not a reducing sugar

- The second glucose

- Its anomeric C remains free. Therefore, it is a reducing sugar

Reducing sugars

- ribose and lactose

- sucrose is non-reducing because doesn't have any reducing free ends, therefore cannot work in benedicts solution

Reducing Properties In oligosaccharides and polysaccharides:

- end w free anomeric C→ Reducing end

- end w anomeric C involved in bonding → Nonreducing end

What is the reducing concept important for? (3)

1. Enzyme recognition

2. Metabolism

3. Polysaccharide BD

Oligosaccharides Common abbreviations

Glc = Glucose

Gal = Galactose

Man = Mannose

Fru = Fructose

Fuc = Fucose

GlcN = Glucosamine

GlcNAc = N-acetylglucosamine

Naming Rule

- Sugars written from right to left

- Linkage positions indicated by carbon numbers

- anomeric form (alpha or beta)

Examples:

Gal(β1→4)Glc → Lactose

Glc(α1→4)Glc → Maltose

Glc(α1 β2)Fru → Sucrose

Structural Diversity of Oligosaccharides

- may be Linear or Branched

- Frequently attached to Proteins → Glycoproteins OR Lipids → Glycolipids (mostly in outer cell MB)

Polysaccharides Definition

- Polymers containing >20 monosaccharide units

- Also called glycans: Mannans → polymers of mannose; Galactans → polymers of galactose

- may be linear OR branched

Homopolysaccharides (classification of polysaccharides)

one type of monosaccharide

Heteropolysaccharides (classification of polysaccharides)

more than one type

Plant Storage Form of Glucose

starch

Starch

- storage polysaccaride in plants

- composed of 2 polymers

- 2 types: amylose & amylopectin

Amylose

- Linear polymer/unbranched

- α(1→4) linkages

- Molecular weight: thousands to millions

- Helical structure

Amylopectin

- Branched polymer: Branch points α(1→6) and branch every 24-30 glucose units

- Backbone: α(1→4)

- Up to 10⁶ glucose residues

Ratio of amylose:amylopectin

varies by plant source

Amylopectin storage

Stored as granules in chloroplasts & tubers (e.g., potato, yam)

Animal Storage Form of Glucose

Glycogen

Glycogen

- storage of starch in animals

- similar structure to amylopectin

glycogen structure

- Backbone: α(1→4)

- Branches: α(1→6), More highly branched: every 8-12 residues

- Up to 50,000 glucose residues

- always attach to protein molecule (like enzyme)

glycogen abundance

Especially abundant in liver (~7% liver weight)

Glycogen Functional Significance of Branching

-One reducing end & Many nonreducing ends

- Enzymes (Glycogen phosphorylase) remove glucose from nonreducing ends, allowing rapid, simultaneous glucose release

Glycogen Structural Organization

- Exists as granules in liver cells

- Reducing end attached to Glycogenin

Glycogenin

- Structural anchor

- Enzyme involved in synthesis of glycogen

Why Store Glucose as Glycogen?

- Free glucose at equivalent levels → ~0.4 M concentration

- Would cause: High osmolarity, Water influx, Cell rupture

solution to cell rupturing

Glycogen: Insoluble, Low osmotic impact (conc goes down)

- Facilitates glucose uptake from blood (~5 mM extracellular)

Cellulose

Linear glucose polymer

- structural polysaccharide

cellulose structure

- β(1→4) linkages

- 10,000-15,000 glucose units

- Strong hydrogen bonding bw chains

cellulose characteristics

- Water insoluble

- Major component of plant cell wall

- Most abundant polysaccharide in nature

- Cotton = nearly pure cellulose

- Most animals cannot digest (lack enzyme for β-linkage cleavage)

Chitin

Linear homopolysaccharide

- structural polysaccharide

chitin structure

- Monomer: N-acetylglucosamine

- β(1→4) linkage

Chitin characteristics

- Structural component of insect exoskeleton & crustacean shells

- Provides rigidity and protection

Bacterial & Extracellular Matrix Carbohydrates

Peptidoglycans, Proteoglycans

Peptidoglycans

- Linear heteropolymers

- Bacterial Cell Wall

Peptodoglycan structure

- Alternating N-acetylglucosamine (GlcNAc) & N-acetylmuramic acid (MurNAc)

- Linked by β(1→4) glycosidic bonds

- Cross-linked by short peptide chains

peptidoglycan functions (3)

1. Provide structural strength

2. Prevent osmotic swelling and lysis

3. Especially important in Gram-positive bacteria

Proteoglycans structure

- Core protein + glycosaminoglycan (GAG) chains

- GAGs = long, unbranched heteropolysaccharides

proteoglycans characteristics/functions

- Major components of extracellular matrix (ECM)

- Highly hydrated → provide cushioning & lubrication