Biochemistry: Carbohydrates and Polysaccharides

Biochemistry I - CHM219

• Course instructor: Dr. Esra Aydemir
• Course title: Biochemistry I
• Course code: CHM219

Carbohydrates: Sugars, Saccharides, Glycans

• Carbohydrates have various functions in biochemistry, including generating and storing biological energy, molecular recognition (e.g., in the immune system), cellular protection (e.g., in bacterial and plant cell walls), cell signaling, cell adhesion, biological lubrication, controlling protein trafficking, and maintaining biological structure (e.g., cellulose).
• Monosaccharides are the simplest carbohydrates.
  • Glucose is a monosaccharide.
  • Maltose is a disaccharide containing two glucose units.
  • Amylose is a glucose polymer found in starch.

Outline

• Monosaccharides
• Derivatives of the Monosaccharides
• Oligosaccharides
• Polysaccharides
• Glycoproteins
• Oligosaccharides as Cell Markers
• Biosynthesis of Glycoconjugates-Amino Sugars
• Glycoconjugates of Interest

Monosaccharides

• Trioses are the simplest monosaccharides.
• Aldoses and ketoses differ in the placement of the carbonyl group (aldehyde vs. ketone).
• Carbon numbering in aldoses begins with the aldehyde carbon, while in ketoses it begins with the carbon adjacent to the ketone group.
• D and L isomers are nonsuperimposable mirror images and are called enantiomers.
• D-enantiomers are the most important naturally occurring saccharides.

R-S Nomenclature

• The R-S system describes absolute stereochemical configuration according to defined rules.
• Priorities for groups common in carbohydrate chemistry are: SH > OR > OH > NH₂ > CO₂H > CHO > CH₂OH > CH₃ > H.
• View the molecule with the lowest priority group (usually H) away from you.
• If remaining groups decrease in priority in a clockwise direction, the absolute configuration is R.
• If priority decreases counterclockwise, the configuration is S.

Oxidation of Monosaccharides

• Oxidation of monosaccharides can create different products depending on the oxidizing agent used.
• Mild oxidation with alkaline Cu(II) (Fehling's solution) produces aldonic acids.
• Enzyme-catalyzed oxidation can produce uronic acids, such as glucuronic acid.
• Free aldonic acids can exist in equilibrium with lactones in solution.

Reduction of Monosaccharides

• Reduction of the carbonyl group on a sugar forms alditols.
• Important alditols include erythritol, mannitol, and sorbitol (glucitol).

Amino Sugar Derivatives

• Some amino sugars are widely distributed in natural polysaccharides.
• Examples include glucosamine and galactosamine derived from glucose and galactose

Glycosidic Bonds

• Elimination of water between an anomeric hydroxyl group of a cyclic monosaccharide and the hydroxyl group of another compound forms O-glycosidic bonds.
• These bonds are important in oligosaccharides and polysaccharides.

Oligosaccharides

• Two naturally occurring glycosides are ouabain and amygdalin, which are highly toxic.
• Disaccharides include lactose, sucrose, maltose, cellobiose and gentiobiose, each with varying structures.
• The distinguishing features of disaccharides include the specific sugar monomers, stereoconfigurations, the carbons involved in the linkage, the order of the monomers, and the configuration of the anomeric hydroxyl groups.

Glycoproteins

• Oligosaccharides and proteins can form glycoproteins in two ways: O-linked glycans are attached via threonine or serine hydroxyls, and N-linked glycans are via asparagine groups.

The ABO Blood Group Antigens

• The O oligosaccharide does not elicit antibodies in most humans.
• The A and B antigens are formed by the addition of GalNAc or Gal respectively, to the O oligosaccharide.
• Each antigen elicits a specific antibody.
• R can be a protein molecule or a lipid molecule.

Polysaccharides

• Starch (amylose and amylopectin) and glycogen are the principal storage polysaccharides in cells.
• Glycogen is primarily stored in the liver and muscles.
• Starch and glycogen are storage polysaccharides, making them important sources of energy for many organisms.
• Amylose is linear, while amylopectin and glycogen are branched.

Cellulose

• Cellulose is a structural polysaccharide in plants.
• Its (1→4) β-linkages make it a strong and structurally rigid polymer
• Another structural polysaccharide is chitin.

Organization of Plant Cell Walls

• Microfibrils of cellulose embedded in a matrix of hemicellulose.
• Cross-hatched fiber patterns give strength in all directions.

Glycosaminoglycans

• Major structural polysaccharides in vertebrate animals are glycosaminoglycans.
• Examples include the chondroitin sulfates, keratan sulfates, dermatan sulfates, and hyaluronic acid.
• All are repeating disaccharide units with either N-acetylgalactosamine, N-acetylglucosamine, or their derivatives.
• All are acidic due to sulfate or carboxylate groups.

Heparin

• A highly sulfated glycosaminoglycan used as a natural anticoagulant.
• It inhibits blood clotting enzymes.

Peptidoglycan

• Cell walls of Gram-positive bacteria (e.g., S. aureus) are composed of thick peptidoglycan layers.
• Peptides are cross-linked by glycine pentapeptides in the cell wall.

Gram-negative bacteria

• Cell walls of Gram-negative bacteria (e.g., E. coli) contain a thin peptidoglycan layer and an outer lipid membrane.
• Cross-links between tetrapeptides attached to NAM reside in adjacent chains.

Lipoteichoic Acid

• D-Alanyl and NAG groups are arranged irregularly in a chain.
• The chain is anchored in the membrane by lipid.

Influenza Virus Structure

• The influenza virus has a 13,600-nucleotide RNA genome packaged in a sphere about 120 nanometers in diameter.
• Spikes on the virion include hemagglutinin and neuraminidase molecules.

Rational Design of Neuraminidase Inhibitors

• Structures of sialic acid, zanamivir and oseltamivir
• Partial models of the neuraminidase-zanamivir complex show critical amino acid residues near the inhibitor binding site

Oligosaccharides as Cell Markers

• Animal cells have a glycocalyx, a thick sugar coat.
• Glycocalyx oligosaccharides interact with substances like bacteria in the intestine and collagen in the intercellular matrix.

Imaging Cell Surface Glycoproteins

• Zebrafish embryos can incorporate an azido derivative of GaINAc for imaging cell surface glycoproteins.
• Fluorescent reagents allow visualization of glycoproteins in living cells.

Biosynthesis of Glycoconjugates - Amino Sugars

• UDP-N-acetyl glucosamine is synthesized from glucosamine-6-phosphate.
• UDP-N-acetylneuraminic acid (sialic acid) is synthesized from UDP-N-acetylglucosamine.

Structures of N-linked Oligosaccharides

• The red boxes in the image outline the common pentasaccharide core
• All known N-linked structures share this core.

Glycoconjugates of Interest

• Biosynthesis of the lipid-linked oligosaccharide intermediate.
• The five sequential mannosyl transfer reactions from GDP -mannose.
• Four mannosyl transfers from dolichol phosphate mannose are catalyzed by separate glycosyltransferases.
• The lipid-linked oligosaccharide is synthesized in the ER and transferred to the glycoprotein acceptor site.
• Schematic pathway of oligosaccharide processing on newly synthesized glycoproteins.

Synthesis of Linear Peptidoglycan Molecule of S. aureus

• The peptidoglycan molecule is formed by adding N-acetylglucosamine and five glycyl residues to N-acetylmuramylpentapeptide.
• Undecaprenol phosphate acts as a carrier.

Cross-linking Reaction in Peptidoglycan Synthesis

• Cross-links between adjacent peptidoglycan chains are formed by transpeptidase enzymes.
• Penicillin structurally mimics the peptide substrate to inactivate the enzyme.

Biosynthesis of the Repeating Oligosaccharide Unit of the O Antigen of Salmonella Typhimurium

• First four reactions occur in the inner membrane.
• Activated tetrasaccharide unit is transferred to the unactivated terminus of a growing polysaccharide unit on the outside of the outer membrane.

This quiz focuses on the structure and functions of carbohydrates, including glycogen, amylopectin, and various polysaccharides. Explore concepts such as monosaccharides, linkages in structural polysaccharides, and the role of carbohydrates in biological systems.