Chapter 7: Carbohydrates and Glycobiology

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Chapter 7Carbohydrates and Glycobiology

• Dr. Clower
• Chem 4202

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Outline, part 1 (sections 7.1-7.2)

• Types of Carbohydrates
• Monosaccharides
• Classification
• Stereochemistry
• Structure
• Chemical Properties
• Disaccharides
• Structure
• Nomenclature
• Polysaccharides
• Structural
• Storage

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Carbohydrates

• Most abundant organic compounds in nature
• A major source of energy from our diet
• Composed of the elements C, H and O
• Synthesized from CO2, H2O
• aka saccharides, which means sugars
• In general, empirical formula (CH2O)n where n 3

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Types of Carbohydrates

• Monosaccharides
• Cannot be hydrolyzed to give a smaller
  carbohydrate
• Simple carbohydrates
• Complex carbohydrates
• Disaccharides two monosaccharides
• Polysaccharides many monosaccharides

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Classification of Monosaccharides

• Monosaccharide
• Unbranched chain of 3-8 C atoms
• One is carbonyl others attached to -OH
• Aldoses
• contain an aldehyde group (carbon 1)
• Ketoses
• contain a ketone group (carbon 2)

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Monosaccharides

• Classification according to the number of C atoms
• triose three carbons
• tetrose four carbons
• pentose five carbons
• hexose six carbons, etc.

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Learning Check

• Classify the following monosaccharides

A B
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Fischer Projections

• Used to represent carbohydrates (chiral carbons)
• Places the most oxidized group at the top (C1)
• Uses horizontal lines for bonds that come forward
• Uses vertical lines for bonds that go back

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D and L Notations

• By convention, the letter L is assigned to the
  structure with the OH on the left
• The letter D is assigned to the structure with
  OH on the right

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D and L Monosaccharides

• Stereochemistry determined by the asymmetric
  center farthest from the carbonyl group
• Most monosaccharides found in living organisms
  are D

D
D
L
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Learning Check

• Indicate whether each is the D or L
  isomer
• Ribose Threose
  Fructose

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Epimers

• Sugars that differ at only one stereocenter

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D-Glucose

• Most common hexose
• Found in fruits, corn syrup, and honey
• An aldohexose with the formula C6H12O6
• Known as blood sugar in the body
• Building block for many disaccharides and
  polysaccharides

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Blood Glucose Level

• In the body, glucose has a normal concentration
  of 70-90 mg/dL
• Depends on time since last meal (rise after eat
  decrease as used or stored)
• In a glucose tolerance test, blood glucose is
  measured for several hours after ingesting glucose

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D-Fructose

• Ketohexose C6H12O6
• Differ from glucose at C1 and C2 (location of
  carbonyl)
• The sweetest carbohydrate (2x sucrose)
• Found in fruit juices and honey
• Formed from hydrolysis of sucrose
• Converts to glucose in the body

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D-Galactose

• Aldohexose
• Differ from D-glucose at C4
• Not found in the free form in nature
• Obtained from lactose, a disaccharide (milk
  products)
• Important in cellular membranes in CNS

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Memorize!
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Memorize!
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Hemiacetal Review

• What is a hemiacetal?
• How is a hemiacetal formed?
• What if the alcohol and carbonyl are attached?

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Hexose hemiacetals

• Favor formation of 5- or 6-membered rings
• Hydroxyl group on C5 reacts with the aldehyde or
  ketone
• Haworth perspective formulas
• Can be written from the Fischer projection
• C1 drawn on the right (anomeric C)
• The cyclic structure of a D-isomer has the last
  CH2OH group located above the ring (C6)
• OH groups on the left are drawn up (C3)
• OH groups on the right are drawn down (C2, C4)

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Pyranose

• Analogous to Pyran

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Anomers

• The carbonyl carbon is the anomeric carbon
• Becomes chiral in Hayworth perspective formulas
• Anomers
• Isomers which differ in placement of hydroxyl on
  C1
• Slightly different chemical and physical
  properties
• ?-anomer
• -OH on anomeric C on opposite side of ring from
  CH2OH
• down for D-sugars
• b-anomer
• -OH on anomeric C on same side of ring as CH2OH
• up for D-sugars

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? and ? Anomers for D-Glucose
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Cyclic Structure of Fructose

• As a ketohexose, fructose forms a cyclic
  structure when the OH on C5 reacts with the
  ketone on C2
• Result is 5-atom ring
• Anomeric carbon is C2
• A furanose analogous to furan

?-D-Fructose
?-D-Fructose
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Pyranoses and Furanoses
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Mutarotation

• In solution, anomers interconvert (slowly)
• Mutarotation involves the conversion of the
  cyclic anomers into the open chain
• At any time, there is only a small amount of
  linear saccharide

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Stability of Anomer Conformations

• Pyranose rings are not planar
• The most stable chair conformation will dominate

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Learning Check

• Write the cyclic form of ?-D-galactose

?-D-galactose
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Sugar Derivatives

• Formed from reactions of sugar
• Carbonyl
• linear form
• Hydroxyl groups
• Linear or ring, depending on reaction
• Some common derivatives
• Oxidation of 1 alcohol of aldose
• Formation of uronic acids (uronate)
• Deoxy sugars replace OH with H
• Amino sugars replace OH with NH2
• Can be acylated (-NH-C(O)-CH3)

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Some Hexose Derivatives
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ReviewReactions of aldehydes

• Oxidation to form carboxylic acids
• Reduction to form alcohols
• Formation of hemiacetal
• Hemiacetal alcohol ? acetal

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Other common derivatives

• Oxidation of aldehyde of aldose
• Aldonic acids
• Reduction of carbonyl of aldose or ketose
• Alditols
• Condensation reactions between anomeric OH and
  alcohols to form acetals or ketals
• Glycosides

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Oxidation of Monosaccharides

• Aldose ? aldonic acid

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Reducing Sugars

• Reducing sugars
• Free anomeric carbon
• Benedicts test
• Carbonyl group oxidized to give carboxylic acid
• Copper ion is reduced

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Reduction of Monosaccharides

• The reduction of the carbonyl group produces
  sugar alcohols, or alditols
• D-Glucose is reduced to D-glucitol (also called
  sorbitol)

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Learning Check

• Write the products of the oxidation and
  reduction of D-mannose.

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Glycosides and Glycosidic Bonds

• When a cyclic monosaccharide reacts with an
  alcohol
• A glycoside is produced (acetal)
• The bond is a glycosidic bond (a or b)
• ?-D-Glucose Methanol
  Methyl-?-D-glucoside

H2O
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Polysaccharides

• aka glycans
• Complex carbohydrates
• Monosaccharides linked by glycosidic bonds
• Can be branched (unlike polypeptides)
• Homopolysaccharides
• One type of monosaccharide
• Heteropolysaccharides
• gt 1 type of monosaccharide
• Repetitive sequence
• Structure determined by hydrolysis (glycosidase)
  and NMR

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Disaccharides

• Simplest polysaccharide
• Consists of two monosaccharides
• Disaccharide Monosaccharides
• Maltose H2O Glucose Glucose
• Lactose H2O Glucose Galactose
• Sucrose H2O Glucose Fructose

H
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Maltose

• Malt sugar
• A disaccharide in which two D-glucose molecules
  are joined by an ?-1,4-glycosidic bond
• Obtained from starch
• Used in cereals, candies, and brewing
• A reducing sugar

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Naming Disaccharides

• Non-reducing end on the left
• Give configuration (a or b) at anomeric carbon
  joining residues
• Name non-reducing residue
• Add furano or pyrano
• Glycosidic bond in parenthesis ( ? )
• Name second residue

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Lactose and Sucrose

• Lactose
• Milk sugar
• Galactose and glucose
• ?-1,4-glycosidic bond
• Lactose intolerance
• A reducing sugar
• Sucrose
• Table sugar
• Glucose and fructose
• ?,?-1,2-glycosidic bond
• Has no isomers
• mutarotation is blocked
• Not a reducing sugar

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Sweetness of Sweeteners

• Sugars and artificial sweeteners differ in
  sweetness
• Each sweetener is compared to sucrose (table
  sugar), which is assigned a value of 100
• Aspartame
• Components?
• Danger to phenylketonurics

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Polysaccharides

• Polymers of D-glucose
• Structural
• Cellulose
• Chitin
• Storage
• Starch (Amylose and Amylopectin)
• Glycogen
• Glucosaminoglycans

D-Glucose
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Cellulose

• Plant cell walls
• Linear polymer
• Up to 15000 Glc residues
• ?-1?4 glycosidic bonds
• Exceptionally strong fiber
• Water insoluble (no room for water to H-bond)
• Hydrolyzed by cellulases (slowly)
• Found in herbivores, termites, wood fungi

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Cellulose Structure

• Parallel extended chains
• Intrachain H-bonds
• Sheets stack vertically

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Chitin

• Same as cellulose, except OH on C2 replaced with
  acetamide
• Amino sugar
• Homopolymer of N-acetyl-D-glucosamine
• Very strong
• Structural component of exoskeleton of arthropods

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Starch

• Main carb in human diet
• Primary source of energy in many foods
• Composed of amylose (20) and amylopectin (80)
• Amylose
• Continuous chain linked by ?-1,4 glycosidic bonds
• Forms left-handed helix
• Amylopectin
• Branched chain ( every 25 residues) linked by
  ?-1,4- and ?-1,6-glycosidic bonds

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Glycogen

• Same function (as starch) in animals
• Similar to amylopectin, but more highly branched

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Hydrolysis of polysaccharides

• Mashed potatoes or mashed paper?
• Enzymes in saliva and stomach (amylase, a
  glycosidase) can hydrolyze ?-1,4 glycosidic bonds
  in starch, but not ?-1,4 glycosidic bonds in
  cellulose

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Folding of Polysaccharides

• Maximize H-bonding, minimize steric strain

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Glycosaminoglycans

• Gel-like matrix surrounding collagen in
  cartilage, tendons, skin
• Unbranched polysaccharides
• High elasticity and viscosity
• Alternating uronic acid and hexosamine
• Frequently contain sulfate groups

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Glycosaminoglycans
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Summary of Polysaccharides
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Outline, part 2 (sections 7.3, 7.5)

• Glycoconjugates
• Glycolipids
• Glycoproteins
• Proteoglycans
• Peptidoglycans
• Determination of carbohydrate structure

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Glycoconjugates

• Covalent bond between carbohydrate and
  biomolecule
• Glycoproteins
• Glycolipids
• Function of oilgosaccharides
• Structural
• Hydrophilic (protein surface)
• Limit conformations
• Reactivity
• Shield surface and affect reactivity
• Surface Recognition
• Label proteins
• Intracellular communication

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Glycolipids

• Membrane lipids
• Hydrophilic heads are oligosaccharides
• Recognition sites

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Glycoproteins

• Proteins with carbohydrates
• Microheterogeneity
• Variable composition
• Range from 1-90
• Large array of functions
• Structure, transport, enzymes, receptors, etc.
• Carbohydrate chains
• Often short (oligosaccharide)
• May be branched
• Synthesized by enzymatic reaction
• Covalently linked to polypeptide

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Proteoglycans

• Extracellular aggregate of protein and
  glycosaminoglycans
• Core protein
• Oligosaccharide glycosidic bond to O of Ser or Thr

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Proteoglycan Aggregates

• Backbone
• 4000-40000 Å
• Single hyalurnoate molecule
• Core proteins
• Up to 100
• Many types
• Oligosaccharides
• N-linked
• O-linked
• Sulfonated
• Highly hydrated
• Anionic
• Extended structure
• High resilience

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N- and O-linkages
b-glycosidic bond
a-glycosidic bond
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Peptidoglycan

• Bacterial cell walls
• Covalently linked polysaccharide and polypeptide
  chains
• D-AAs resist hydrolysis by peptidases
• Lysozyme can break down cell wall
• Penicillins can prohibit synthesis (cross-linking)

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Determination of Structure
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Chapter 7 Problems

• 2-5, 8-11, 13-17