Chapter 7: Carbohydrates and Glycobiology

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Chapter 7: Carbohydrates and Glycobiology Powered By Docstoc
					    Chapter 7:
Carbohydrates and
  Glycobiology
    Dr. Clower
    Chem 4202
Outline, part 1 (sections 7.1-7.2)
   Types of Carbohydrates
       Monosaccharides
            Classification
            Stereochemistry
            Structure
            Chemical Properties
       Disaccharides
            Structure
            Nomenclature
       Polysaccharides
            Structural
            Storage
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 (C·H2O)n where n ≥ 3
Types of Carbohydrates
  Monosaccharides
     Cannot be hydrolyzed to give a smaller carbohydrate
     Simple carbohydrates
  Complex carbohydrates:
     Disaccharides: two monosaccharides
     Polysaccharides: many monosaccharides
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)
                                                      CH2OH
                                                        O
                               CHO             HO       H
             CHO
                         HO      H                H     OH
        HO     H
                           H     OH               H     OH
             CH2OH
                               CH2OH                  CH
                                                      OH 2OH
Monosaccharides
   Classification according to the number of C atoms
       triose = three carbons
       tetrose = four carbons
       pentose = five carbons
       hexose = six carbons, etc.
                                             CH2OH
                                               O

                                CHO     HO     H
          CHO             HO      H     H      OH
     HO      H              H     OH    H      OH
          CH2OH                 CH2OH        CH
                                             OH 2OH
Learning Check
Classify the following monosaccharides:


                                  CH2OH
         CHO                          O
    HO       H              HO        H
    HO       H                H       OH
    HO       H                H       OH
         CH2OH                    CH2OH
         A                        B
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
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
D and L Monosaccharides
   Stereochemistry determined by the asymmetric
    center farthest from the carbonyl group
   Most monosaccharides found in living organisms
    are D                  O                  O
                           C   H              C OH
          CHO
                       H       OH        HO       H
      H      OH
      H      OH       HO       H          H       OH
      H      OH        H       OH         H       OH
          CH 2OH       H       OH        HO       H
           D
          D-Ribose         CH2OH             CH2OH
                           D              L
                                          L-Galactose
                           D-Glucose
Learning Check
   Indicate whether each is the D or L isomer:

                                           CH2OH
         CHO
                          CHO                O
    HO     H
                      H     OH       HO      H
    HO     H
                    HO      H          H     OH
    HO     H
                          CH2OH        H     OH
         CH2OH
                                           CH2OH
     Ribose           Threose           Fructose
Epimers
   Sugars that differ at only one stereocenter
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
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
D-Fructose
   Ketohexose C6H12O6
   Differ from glucose at C1 and C2
    (location of carbonyl)
                                           CH2OH
   The sweetest carbohydrate (2x
    sucrose)                               C O
   Found in fruit juices and honey     HO C H
   Formed from hydrolysis of sucrose   H C OH
   Converts to glucose in the body     H C OH
                                           CH2OH

                                         D-Fructose
D-Galactose
   Aldohexose
   Differ from D-glucose at C4      CHO
   Not found in the free form    H C OH
    in nature                     HO C H

   Obtained from lactose, a      HO C H

    disaccharide (milk            H C OH

    products)                        CH2OH

   Important in cellular           D-Galactose
    membranes in CNS
Memorize!
Memorize!
Hemiacetal Review
   What is a hemiacetal?
   How is a hemiacetal formed?
                           O                                                 OH
                                                                   +
                                                               H
                     CH3   C   H       +       CH3OH                   CH3   C       H


                                                                             OCH3



   What if the alcohol and carbonyl are attached?
                                                               H
                                                                                                 H
                               O                       O
                                                                   O                     O
                                                                        H+                           O
                                           =               C
                               C                                                             C
        HO                         H                           H
                                                                                                 H


                                       HOCH2
                                                                             HOCH2
                                                               H
                                                                                                 H
             CH2OH             O                       O
                                                                   O                     O
                                                                        H+                           O
                                           =               C
                               C                                                             C
        HO                         H                           H
                                                                                                 H
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)
Pyranose


       6 CH2OH
                                  Analogous to Pyran
       5         O
   H
                          H
        H
  4              H    1                     O
        OH
                          OH
  OH
           3     2

        H        OH
                                           pyran
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
                                 6 CH2OH

                                 5         O
                            H
                                                     H
                                  H
                            4              H     1
                                  OH
                                                     OH
                            OH
                                     3     2

   -anomer                      H        OH


       -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
 and b Anomers for D-Glucose
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
                                         O
    Anomeric carbon is C2
    A furanose: analogous to furan
                                           furan
      CH2OH
      C O             CH2OH      CH2OH   CH2OH      OH
                           O                  O
HO C H                         OH                  OH
 H C OH                          OH                 CH2OH
 H C OH                OH                 OH

      CH2OH
    D-Fructose        -D-Fructose        b-D-Fructose
Pyranoses and Furanoses
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
Stability of Anomer
Conformations

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


              HO
                                      OH                 H OH

                        OH                                          H   O
               H             O             H   HO
          H                           H             HO                           OH
                                                                H       OH
                    H

               OH                OH                        H                 H
Learning Check
Write the cyclic form of -D-galactose:

    H       O
        C
   H C OH
  HO C H
  HO C H
   H C OH
        CH2OH
                           -D-galactose
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)
Some Hexose Derivatives
Review:
Reactions of aldehydes
   Oxidation to form carboxylic acids
   Reduction to form alcohols
   Formation of hemiacetal
   Hemiacetal + alcohol → acetal
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
Oxidation of Monosaccharides
   Aldose → aldonic acid
Reducing Sugars
   Reducing sugars
       Free anomeric carbon
   Benedict’s test
       Carbonyl group oxidized to give carboxylic acid
       Copper ion is reduced

               O       H              O       OH
                   C                      C
               H C OH                H C OH
             HO C H                 HO C H
                           + Cu2+                     + Cu2O(s)
               H C OH                H C OH
               H C OH                H C OH
                   CH2OH                  CH2OH

              D-Glucose             D-Gluconic acid
Reduction of Monosaccharides

   The reduction of
    the carbonyl
    group produces
    sugar alcohols, or
    alditols
   D-Glucose is
    reduced to D-
    glucitol (also
    called sorbitol)
Learning Check
 Write the products of the oxidation and
 reduction of D-mannose.


                     O
                     C H
                HO       H
                HO       H
                 H       OH
                 H       OH
                     CH2OH
                 D-Mannose
Glycosides and
Glycosidic Bonds
   When a cyclic monosaccharide reacts with an
    alcohol:
       A glycoside is produced (acetal)
       The bond is a glycosidic bond ( or b)

                                                       glycosidic bond
         CH2OH                               CH2OH
               O                                  O    O CH3
                    OH

         OH              + HOCH3             OH                   + H2O
    OH                                  OH

               OH                                 OH

        b-D-Glucose      Methanol      Methyl-b-D-glucoside
Polysaccharides
   aka glycans
   Complex carbohydrates
   Monosaccharides linked by
    glycosidic bonds
   Can be branched (unlike
    polypeptides)
   Homopolysaccharides
       One type of monosaccharide
   Heteropolysaccharides
       > 1 type of monosaccharide
       Repetitive sequence
   Structure determined by
    hydrolysis (glycosidase) and NMR
Disaccharides
   Simplest polysaccharide
   Consists of two monosaccharides


     Disaccharide              Monosaccharides
                         H+
   Maltose + H2O             Glucose + Glucose
   Lactose + H2O             Glucose + Galactose
   Sucrose + H2O             Glucose + Fructose
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
Naming Disaccharides
   Non-reducing end on the left
   Give configuration ( or b) at anomeric carbon
    joining residues
   Name non-reducing residue
       Add furano or pyrano
   Glycosidic bond in parenthesis (# → #)
   Name second residue
Lactose and Sucrose
   Lactose
       Milk sugar
       Galactose and glucose
       b-1,4-glycosidic bond
       Lactose intolerance
       A reducing sugar
   Sucrose
       Table sugar
       Glucose and fructose
       ,b-1,2-glycosidic bond
       Has no isomers
            mutarotation
             is blocked
       Not a reducing sugar
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

                                HO

                     H2N             O




                 O

             O             NH




             O
Polysaccharides
   Polymers of D-glucose
   Structural:
                                                6 CH2OH

       Cellulose                          H
                                                5         O
                                                                   H

        Chitin
                                                 H
                                          4
                                                 OH       H    1

                                                                   OH

    Storage
                                           OH
                                                   3     2

                                                 H        OH

       Starch (Amylose and Amylopectin)
       Glycogen
                                                D-Glucose
   Glucosaminoglycans
Cellulose
   Plant cell walls
   Linear polymer
   Up to 15000 Glc residues
   b-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
Cellulose Structure
   Parallel extended
    chains
   Intrachain H-bonds
   Sheets stack vertically
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
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
Glycogen
 Same function (as starch) in animals
 Similar to amylopectin, but more highly
  branched
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 b-1,4
    glycosidic bonds in cellulose
Folding of Polysaccharides
   Maximize H-bonding, minimize steric strain
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
Glycosaminoglycans
Summary of Polysaccharides
Outline, part 2 (sections 7.3, 7.5)
   Glycoconjugates
       Glycolipids
       Glycoproteins
            Proteoglycans
            Peptidoglycans

   Determination of carbohydrate structure
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
Glycolipids
   Membrane lipids
   Hydrophilic heads are
    oligosaccharides
   Recognition sites
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
Proteoglycans
   Extracellular aggregate of
    protein and
    glycosaminoglycans
   Core protein
   Oligosaccharide glycosidic
    bond to O of Ser or Thr
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
N- and O-linkages


                    b-glycosidic
                        bond
-glycosidic
    bond
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)
Determination of Structure
Chapter 7 Problems
   2-5, 8-11, 13-17

				
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