Carbohydrate Structure and Function Study Notes

Carbohydrate Structure

Definition of Carbohydrates

• Carbohydrates: Defined as aldehydes or ketones with at least two hydroxyl groups or substances yielding such compounds upon hydrolysis.

• Many carbohydrates exhibit the empirical formula:
  $(CH<em>2O)</em>n$

Classes of Carbohydrates

• Monosaccharides: Simple sugars consisting of a single polyhydroxy aldehyde or ketone unit.

  • Example: D-glucose

• Oligosaccharides: Short chains of monosaccharide units (residues) linked by glycosidic bonds.

• Disaccharides: Special type of oligosaccharide composed of two monosaccharide units.

  • Example: Sucrose (formed from D-glucose and D-fructose)

• Polysaccharides: Sugar polymers containing 10 or more monosaccharide units.

  • Example:

  • Cellulose (linear structure)

  • Glycogen (branched structure)

Stereoisomerism in Sugars

• Stereoisomers arise because many carbon atoms attached to the hydroxyl groups are chiral centers.

• Enzymes that act on sugars demonstrate stereospecificity.

• Stereochemistry provides functional variety in carbohydrates.

Families of Monosaccharides: Aldoses and Ketoses

• Backbones of monosaccharides consist of:

  • Unbranched carbon chains linked by single bonds.

  • One carbon atom double-bonded to an oxygen atom, forming a carbonyl group.

  • Other carbon atoms bonded to hydroxyl groups.

Aldoses and Ketoses

• Aldose: Carbonyl group is located at the end of the carbon chain (aldehyde group).

• Ketose: Carbonyl group resides in any other position (ketone group).

Monosaccharide Types

• Trioses: Simplest monosaccharides with a three-carbon backbone.

  • Example:

  • D-Glyceraldehyde (an aldotriose)

  • Dihydroxyacetone (a ketotriose)

• Tetroses: Monosaccharides with a four-carbon backbone.

• Pentoses: Five-carbon backbone, components of RNA and DNA.

• Hexoses: Six-carbon backbone.

  • Example: D-Glucose (an aldohexose), D-Fructose (a ketohexose)

• Heptoses: Seven-carbon backbone.

Sweetness of Sugars

• Sweetness is mediated by TAS1R2 and TAS1R3, which encode sweet-taste receptors.

• The binding of compatible molecules generates an electrical signal interpreted as “sweet” by the brain, requiring a steric match.

Asymmetric Centers in Monosaccharides

• All monosaccharides (except dihydroxyacetone) contain at least one chiral carbon atom, leading to optically active isomeric forms.

• Enantiomers: Optical isomers that are mirror images of each other.

• Generally, a molecule with $n$ chiral centers has $2^n$ stereoisomers.

Fischer Projection Formulas

• Used to represent three-dimensional sugar structures on paper.

  • Horizontal bonds project out of the plane of the paper.

  • Vertical bonds project behind the plane of the paper.

D and L Isomers

• Reference carbon: Chiral center farthest from the carbonyl carbon.

• D isomers: Configuration at the reference carbon matches that of D-glyceraldehyde; appears on the right in projection formula.

  • Common in hexoses of living organisms.

• L isomers: Configuration at the reference carbon aligns with that of L-glyceraldehyde; appears on the left in projection formula.

Common D-Aldoses and D-Ketoses

• D-Aldoses include:

  • D-Glyceraldehyde

  • D-Erythrose

  • D-Glucose

  • D-Galactose

• D-Ketoses include:

  • Dihydroxyacetone

  • D-Fructose

  • D-Ribulose

Epimers

• Epimers: Sugars that only differ in configuration around one carbon atom.

  • Example:

  • D-Mannose and D-Glucose differ at C-2.

  • D-Galactose and D-Glucose differ at C-4.

Cyclic Structures of Monosaccharides

• In aqueous solutions, aldotetroses and all monosaccharides with 5 or more backbone carbon atoms form cyclic structures through a covalent bond between the carbonyl group and a hydroxyl group.

Hemiacetals and Hemiketals

• Hemiacetals or Hemiketals: Formed by the reaction of alcohols with aldehydes or ketones (the product of the first alcohol's addition).

• If both the hydroxyl and carbonyl groups are in the same molecule, a five- or six-membered ring can form.

• Acetal or Ketal: Result from the addition of a second alcohol molecule and involve glycosidic bonds.

Stereoisomers: Alpha and Beta Configurations

• The reaction with the first alcohol creates an additional chiral center (the carbonyl carbon), producing either α or β stereoisomers.

• Anomers: Isomeric forms that differ only in configuration around the hemiacetal or hemiketal carbon.

• Anomeric carbon: The carbonyl carbon atom in cyclic monosaccharides.

Cyclic Forms of D-Glucose

• The reaction between the aldehyde group at C-1 and the hydroxyl group at C-5 forms a hemiacetal linkage.

• Mutarotation: The interconversion process between α and β anomers of monosaccharides.

Pyranoses and Furanoses

• Pyranoses: Six-membered ring compounds formed when the hydroxyl group at C-6 reacts with the carbonyl.

• Furanoses: Five-membered ring compounds formed when the hydroxyl group at C-5 reacts with the carbonyl.

Haworth Perspective Formulas

• Haworth Perspective: Represents cyclic forms in a way that tilts the six-membered ring, making it appear almost perpendicular to the paper.

• Bonds closest to the viewer are thicker than those farther away.

Conformational Structures of Pyranoses

• Pyranose rings often assume two chair conformations that interconvert without breaking covalent bonds but require energy input.

Hexose Derivatives

• Various hexose derivatives exist, including amino sugars, deoxy sugars, and acidic sugars, each with specific structural features.

Reducing Sugars

• Reducing sugars: Undergo redox reactions where free aldehyde groups react with Cu2+, reducing to Cu+ and forming a brick-red precipitate.

• Ketoses that can tautomerize to form aldehydes qualify as reducing sugars.

O-Glycosidic Bonds

• O-Glycosidic bond: Covalent linkage of two monosaccharides formed when a hydroxyl group of one sugar reacts with an anomeric carbon of another.

• Such bonds can be readily hydrolyzed by acid.

Reducing End of Carbohydrates

• Formation of a glycosidic bond designates a sugar as non-reducing.

• The reducing end of a disaccharide or polysaccharide chain is where a free anomeric carbon is located.

Common Disaccharides

• Lactose: A reducing disaccharide.

• Sucrose and Trehalose: Non-reducing sugars.

• Structures include variations in linkage types (e.g., β-D-galactopyranosyl-(1-4)-β-D-glucopyranose for lactose).

Homopolysaccharides and Heteropolysaccharides

• Homopolysaccharides: Composed of a single type of monomer, serving for storage and structural elements.

• Heteropolysaccharides: Composed of multiple types of monomers, providing extracellular support.

Polysaccharides: Length and Molecular Weight

• Polysaccharides generally do not have defined lengths or molecular weights, differing from proteins due to their synthesis mechanisms.

• No template for polysaccharide synthesis exists; it's intrinsic to the enzymes catalyzing polymerization.

Storage Polysaccharides

• Storage polysaccharides include starch in plants and glycogen in animals, which hold significant hydration due to many exposed hydroxyl groups.

Structure of Starch and Glycogen

• Starch consists of two glucose polymers:

  • Amylose: Long, unbranched chains of D-glucose linked by (α1→4) bonds.

  • Amylopectin: Larger with (α1→4) linkages and (α1→6) branches.

• Glycogen: A polymer of (α1→4)-linked glucose, more extensively branched and compact than starch.

Helical Structure of Starch and Glycogen

• The most stable structure for (α1→4)-linked chains forms a helical structure with six residues per turn.

Structural Roles of Homopolysaccharides

• Cellulose: Tough, fibrous, and water-insoluble, composed of linear chains of D-glucose units linked by (β1→4) bonds.

• Mammals cannot hydrolyze (β1→4) bonds due to the absence of the requisite enzyme.

Chitin

• Chitin: Composed of N-acetylglucosamine residues linked by (β1→4) bonds.

• The acetylated amino group enhances its hydrophobic and water-resistant properties compared to cellulose.

Glycosaminoglycans in ECM

• Glycosaminoglycans: Heteropolysaccharides in ECM, composed of repeating disaccharide units. One monosaccharide is N-acetylglucosamine or N-acetylgalactosamine, and the other is a uronic acid.

Peptidoglycan in Bacterial Cell Walls

• Peptidoglycan: Rigid component of bacterial cell walls, alternating between (β1→4)-linked N-acetylglucosamine and N-acetylmuramic acid residues, cross-linked by short peptides.

Determining Carbohydrate Structures

• More complex than proteins, determination methods include traditional chemical, enzymatic methods, mass spectrometry, and high-resolution NMR spectroscopy.

Solid-Phase Synthetic Methods

• Carbohydrate chemists can synthesize segments of glycosaminoglycans, utilizing solid-phase oligosaccharide synthesis principles to yield precise oligosaccharides useful for studying lectin-oligosaccharide interactions.

Glycoconjugates

• Glycoconjugate: Biologically active molecules composed of an informational carbohydrate attached to a protein or lipid.

Glycoproteins

• Glycoproteins: Molecules with one or more covalently attached oligosaccharides. Found on plasma membranes, ECM, blood, and organelles; oligosaccharides provide informational diversity.

Types of Glycoprotein Attachments

• O-linked: Glycosidic bond linking carbohydrate anomeric carbon to an —OH of Ser or Thr residue.

• N-linked: An N-glycosyl bond connecting anomeric carbon of sugar to amide nitrogen of an Asn residue.

Proteoglycans

• Proteoglycan Unit: A core protein connected to covalently attached glycosaminoglycans; a tetrasaccharide linker connects a glycosaminoglycan to a Ser residue of the protein.

Families of Membrane Heparan Sulfate Proteoglycans

• Syndecans: Features a single transmembrane domain and extracellular domain with multiple heparan sulfate and chondroitin sulfate chains.

• Glypicans: Attaches to membranes via GPI anchor.

Fibronectin and Integrins

• Fibronectin: Binds fibrin, heparan sulfate, and collagen; incorporates the RGD sequence (Arg–Gly–Asp) for integrin binding.

• Integrins: Facilitate signaling between cell interiors and ECM molecules.

Glycolipids and Lipopolysaccharides in Membranes

• Gangliosides: Membrane lipids of eukaryotic cells featuring complex oligosaccharide polar head groups.

• Lipopolysaccharides: Major surface features of gram-negative bacterial outer membranes.

Role of Lectins

• Lectins: Proteins that specifically bind carbohydrates, mediating cell-cell recognition and adhesion, signaling, and protein targeting within cells.

Selectin Functions

• Selectins: Plasma membrane lectins facilitating cell-cell recognition and adhesion, critical for immune cell movement, inflammatory responses, and organ transplant rejections.

Lectin-Carbohydrate Interactions

• These interactions are highly specific and often multivalent due to subtle molecular complementarity, enhancing binding accuracy to correct carbohydrate partners.

Hydrophobic Effects in Sugar Interactions

• Sugar interactions occur due to the polar and less polar sides affecting their behavior in various environments.