Carbohydrates and Glycobiology Quiz

Carbohydrates and Glycobiology

• Carbohydrates are aldehydes or ketones with at least two hydroxyl groups, or substances that yield such compounds on hydrolysis. Many carbohydrates have the empirical formula (CH₂O)ₙ.
• Carbohydrates are produced from CO₂ and H₂O via photosynthesis in plants.
• They range in size. Examples include glyceraldehyde (MW = 90 g/mol) and amylopectin (MW > 200,000,000 g/mol).
• Carbohydrates can be covalently linked with proteins and lipids.
• Carbohydrates fulfill many functions, including: (a list of functions is not provided).

Classes of Carbohydrates

• Monosaccharides: Simple sugars; consist of a single polyhydroxy aldehyde or ketone unit. e.g., D-glucose
• Disaccharides: Oligosaccharides with two monosaccharide units; e.g., sucrose (D-glucose and D-fructose)
• Oligosaccharides: Short chains of monosaccharide units, or residues, joined by glycosidic bonds.
• Polysaccharides: Sugar polymers.

Clicker Question 1

• A disaccharide is a(n) oligosaccharide with two monosaccharide units.

Clicker Question 2

• The position of the carbonyl carbon determines if a sugar is an aldose or a ketose.

Monosaccharides

• Monosaccharides have multiple chiral carbons. The configuration of groups around each carbon atom determines how the compound interacts with other biomolecules. Biological evolution selected the D-series for sugars.
• Sugar stereoisomers arise because many of the carbon atoms to which hydroxyl groups are attached are chiral centers. Enzymes that act on sugars are stereospecific.
• Monosaccharides have backbones of carbon chains, all linked by single bonds. One carbon is double-bonded to an oxygen atom. Other carbons are bonded to a hydroxyl group.
• Aldoses have carbonyl groups at an end of the carbon chain (aldehyde group).
• Ketoses have carbonyl groups at any other position (ketone group).

Monosaccharide Carbon Backbone

• 3C = triose
• 4C = tetrose
• 5C = pentose
• 6C = hexose
• 7C = heptose

Trioses

• Simplest monosaccharides; three-carbon backbone.
• Examples: D-glyceraldehyde (aldose) and dihydroxyacetone (ketose)

Tetroses & Pentoses

• Tetroses = four carbon backbone
• Pentoses = five carbon backbone
  • Examples = D-ribose (aldose) and 2-deoxy-D-ribose (aldose).

Hexoses & Heptoses

• Hexose = six carbon backbone
• Heptose = seven carbon backbone

Clicker Question 3

• Glucose is a monosaccharide with a(n) aldehyde functional group and six carbons.

What Makes Sugar Sweet?

• TAS1R2 and TAS1R3 encode sweet-taste receptors.
• Binding of a compatible molecule generates a "sweet" electrical signal in the brain. The interaction requires a steric match.

Clicker Question 4

• (R,S)-aspartame does NOT stimulate the sweet receptor because site X cannot accommodate the hydrophobic benzene ring.

Monosaccharides Have Asymmetric Centers

• All monosaccharides (except dihydroxyacetone) contain one or more chiral carbon atoms and occur in optically active isomeric forms.
• Enantiomers are mirror images.
• A molecule with n chiral centers can have 2ⁿ stereoisomers.

Fischer Projection Formulas

• Used to represent three-dimensional sugar structures on paper.
• Horizontal bonds project out of the plane.
• Vertical bonds project behind the plane.

Enantiomers of Glyceraldehyde

• Displayed as mirror images.

Numbering Carbons of a Sugar

• Numbering begins at the end of the chain near the carbonyl group.

D Isomers and L Isomers

• Reference carbon = chiral center most distant from the carbonyl carbon.
• D-isomers have the configuration at the reference carbon the same as D-glyceraldehyde (on the right).
• L-isomers have the configuration at the reference carbon the same as L-glyceraldehyde (on the left).

Clicker Question 5

• The false statement regarding the enantiomers of glyceraldehyde is that glyceraldehyde does not occur in optically active isomeric forms.

D-Aldoses

• (a list of structures is provided)*

D-Ketoses

• (a list of structures is provided)*

Epimers

• Epimers = two sugars that differ only in the configuration around one carbon atom.
• Examples: D-mannose (epimer at C2) and D-galactose (epimer at C-4) are both epimers of D-glucose.

Structures to Know

• Glyceraldehyde & dihydroxyacetone
• Ribose
• Glucose
• Galactose
• Mannose
• Fructose

(a) D-Aldoses

(structures provided)

(b) D-Ketoses

(structures provided)

Clicker Question 6

• A monosaccharide with a ketone functional group and seven carbons is a ketoheptose.

Hemiacetals and Hemiketals

• Hemiacetals or Hemiketals are derivatives from alcohols and aldehydes/ketones.
• Five or six membered rings can form if the OH and carbonyl groups are on the same molecule.
• Acetal or Ketal is the product from the second alcohol molecule addition to form a glycosidic bond.

α and β Stereoisomeric Configurations

• The reaction with the first alcohol molecule creates an additional chiral center (carbonyl carbon).
• This produces either α (trans) or β (cis) configurations.
• Anomers are isomeric forms of monosaccharides that are different in configuration around the hemiacetals or hemiketals carbon atom.

Clicker Question 7

• Anomers are monosaccharides that differ in configuration around the hemiacetal or hemiketal carbon atom.

Formation of Cyclic Forms of D-Glucose

• A reaction between the aldehyde group at C-1 and the hydroxyl group at C-5 forms a hemiacetal linkage.
• Mutarotation = interconversion of α and β anomers.

Clicker Question 8

• Cyclization of monosaccharides is the reaction of hemiketal or hemiacetal formation.

Pyranoses and Furanoses

• Pyranoses: Six-membered ring compounds where the hydroxyl group at C-6 reacts with the keto group at C-2.
• Furanoses: Five-membered ring compounds where the hydroxyl group at C-5 reacts with the keto group at C-2.

Aldonic and Uronic Acids

• Aldonic acids form following oxidation of the carbonyl carbon of aldoses.
• Uronic acids form following oxidation at C-6.
• Both form stable intramolecular esters called lactones.

Phosphorylated Derivatives

• Some sugar intermediates are phosphate esters (e.g., glucose-6-phosphate).
• These are stable at neutral pH and bear a negative charge.
• This helps to trap sugars inside cells.

Sugars that are, or Can Form, Aldehydes are Reducing Sugars

• Reducing sugars undergo a redox reaction with Cu²⁺ under alkaline conditions. The reduction of Cu²⁺ to Cu⁺ forms a brick-red precipitate.
• Ketoses that can tautomerize to form aldehydes are also reducing sugars.

Chain-Ring Equilibrium & Reducing Sugars

• Rings are in equilibrium with open-chain forms.
• Reducing sugars have a free anomeric carbon. The aldehyde can reduce Cu²⁺ to Cu⁺ (Fehling's test) and Ag+ to Ag⁰ (Tollens' test).
• These tests allow detection of reducing sugars.

Clicker Question 10

• Glucose does not undergo oxidation by reducing sugars.

Blood Glucose Measurements in the Diagnosis and Treatment of Diabetes

• Untreated diabetes has long-term consequences like kidney failure, cardiovascular disease, blindness, etc.
• Average blood glucose over days can be measured due to a nonenzymatic reaction between glucose and primary amino groups in hemoglobin. This is reflected in glycated hemoglobin (GHb).
• Normal levels are ~5% of hemoglobin as GHb. Diabetic levels may reach 13%.

O-Glycosidic Bonds

• O-glycosidic bond = covalent linkage joining two monosaccharides
• The hydroxyl group of one sugar molecule reacts with the anomeric carbon of the other resulting in a glycoside.

The Reducing End

• Formation of a glycosidic bond makes a sugar nonreducing.
• The reducing end of a disaccharide or polysaccharide chain has a free anomeric carbon.

Clicker Question 11

• Non-reducing sugars refer to carbohydrates linked by their anomeric carbons.

Naming Reducing Oligosaccharides

Clicker Question 12

• The name of lactose is β-D-galactopyranosyl-(1→4)-β-D-glucopyranose where the non-reducing end is located on the left, and the configuration of the anomeric carbon is β.

Symbols and Abbreviations for Monosaccharides

• (Table provided explaining common abbreviations for specific monosaccharides)*

Three Common Disaccharides

• Lactose is a reducing disaccharide. Sucrose and Trehalose are non-reducing.

Clicker Question 13

• Trehalose is a non-reducing sugar

Clicker Question 14

• Disaccharides do not always lack free anomeric carbons.

Polysaccharides

• Most carbohydrates in nature occur as polysaccharides (MW > 20,000), also called glycans.

Homopolysaccharides and Heteropolysaccharides

• Homopolysaccharides: Contain only one type of monosaccharide monomer. Serve as storage forms (starch, glycogen) or structural elements (cellulose, chitin).
• Heteropolysaccharides: Contain two or more types of monosaccharide monomers. Provide extracellular support.

Clicker Question 15

• Heteropolysaccharides are not the common form of storage for monosaccharides for energy.

Principle 4

• The order of complex polysaccharides is directed by the biosynthetic enzymes that add each monomeric unit to the growing polymer, contrasted with DNA, RNA, and proteins, which use templates for synthesis.

Polysaccharides Generally Do Not Have Defined Lengths

• Length is not defined; this contrasts with the defined lengths of proteins or DNA sequences. The synthesis program is intrinsic to the enzymes that catalyze the polymerization of monomer units.

Some Homopolysaccharides Are Storage Forms of Fuel

• Storage polysaccharides (starch in plants, glycogen in animals).
• The molecules are heavily hydrated because they have many exposed hydroxyl groups available to hydrogen bond with water.

Starch and Glycogen

• Starch: Contains two glucose polymers, amylose and amylopectin.
  • Amylose: Long, unbranched chains of α(1→4)-linked glucose residues.
  • Amylopectin: Larger than amylose, with α(1→4) linkages and highly branched due to α(1→6) linkages.
• Glycogen: A polymer of α(1→4)-linked glucose subunits, with α(1→6)-linked branches (more extensively branched than amylopectin).

Structure of Starch and Glycogen

(Structures are provided)

Clicker Question 16

• The α(1→4) O-glycosidic bond is common in amylose, amylopectin and glycogen.

Clicker Question 17

• A glycogen molecule with 28 branches has 29 non-reducing ends and 1 reducing end.

Principle 3

• Storage of low molecular weight metabolites as polymers avoids very high osmolarity. This would cause cells to swell and potentially lyse from excess water entry.

Storage of Glucose as Polymers Avoids High Osmolarity

• Hepatocytes in the fed state store glycogen equivalent to 0.4 M glucose.
• 0.4M glucose in the cytosol would elevate the osmolarity causing the cell to swell and potentially lyse.

Clicker Question 18

• Glycogen molecules with many nonreducing ends allow the rapid glucose storage and release.

Some Homopolysaccharides Serve Structural Roles

• Cellulose: Tough, fibrous, water-insoluble substance.
  • Linear, unbranched homopolysaccharide of 10,000-15,000 β(1→4)-linked D-glucose residues.

Clicker Question 19

• The β-glycosidic linkage of glucose molecules in cellulose produces straight, stable fibers that exclude water.

The Challenge of Glycobiology

• Glycobiology is the study of the structure and function of glycoconjugates. The challenge is understanding how cells use specific oligosaccharides to encode information, intracellular targeting of proteins, cell-cell interactions, cell differentiation, and extracellular signals.

Oligosaccharide Structures Are Information-Dense

• Branched structures, not found in nucleic acids or proteins, are common in oligosaccharides.
• Almost limitless variety due to stereochemistry, position of glycosidic bonds, types and orientations of substituent groups, number and type of branches.

Lectins Are Proteins That Read the Sugar Code

• Lectins bind carbohydrates with high specificity and high affinity.
• Functions: cell-cell recognition, signaling, adhesion, and the intracellular targeting of proteins.

Selectins

• Selectins are a family of plasma membrane lectins mediating cell-cell recognition and adhesion in diverse cellular processes.
• they move immune cells through the capillary wall, mediate inflammation, and rejection of transplanted organs.

Clicker Question 30

• Selectins are not intracellular.

Role of Lectin-Ligand Interactions in Leukocyte Movement

(Diagram provided)

Binding Site on Influenza Neuraminidase

(Diagram provided)

Lectin-Carbohydrate Interactions Are Highly Specific

• Subtle molecular complementarity allows interaction only with the lectin's correct carbohydrate binding partners.

Lectin Multivalency

• Single lectin molecules have multiple carbohydrate-binding domains, which increases the effective affinity of the interaction.

Interactions of Sugar Residues Due to the Hydrophobic Effect

(Diagram provided)

Clicker Question 31

• Lectins often bind their ligands via multiple weak interactions.

Biological Interactions Mediated by the Sugar Code

(Diagram provided)