sugars and polysaccharides - mason.gmu.edu
TRANSCRIPT
Sugars and Polysaccharides
March 24, 2015
Sugars and Polysaccharides• Carbohydrates or Saccharides are the most
abundant class of biological molecules.• General formula (C•H2O)n where n≥3. • Monosaccharides are basic building blocks.• Oligosaccharides: a few covalently linked
monosaccharides.• Polysaccharides: many covalently linked
monosaccharides.!
Major Carbohydrate Classes• Monosaccharides
– Single polyhydroxy aldehyde or ketone units• Oligosaccharides
– Short chains of monosaccharides, <20– Most abundant are the disaccharides– Most oligosaccharides of 3 or more units are joined
to nonsugar molecules• Polysaccharides
– Contain more than 20 monosaccharide units– Many contain hundreds or thousands of
monosaccharides– May be in linear (cellulose) or branched (glycogen)
chains
Monosaccharides• Consist of aldehydes or ketones with one or more
hydroxyl groups.• Identified based on the nature of the carbonyl group:
– Aldehyde -> aldose– Ketone -> ketose
• Further classified based on the number of carbon atoms.– 3 -> trioses– 4 -> tetroses– 5 -> pentoses– Etc…
• Often contain multiple chiral centers.– D sugars have the same configuration as does D-glyceraldehyde
at the asymmetric center farthest from the carbonyl group. [Fischer Convention]
– Aldoses generally have 2n-2 stereoisomers.!
CH2OH
CHOH OH
HO CH2OH
CHOH
CH2OH
CHOH OH
D-Glyceraldehyde D-Glyceraldehyde
CH2OH
CHOHO H
H CH2OH
CHOHO
CH2OH
CHOHO H
L-Glyceraldehyde L-Glyceraldehyde
Fischer Projections and Stereochemistry
R
S
Monosaccharide Stereoisomers
• The L sugars are the mirror images of their D isomer counterparts.
• Epimers are stereoisomers that differ only in their configuration at one chiral carbon atom.!
CH2OH
H OH
H OH
HO H
H OH
CHO
CH2OH
HO H
HO H
H OH
HO H
CHO
CH2OH
H OH
H OH
HO H
H OH
CHO
CH2OH
H OH
H OH
HO H
HO H
CHO
D-Glucose L-Glucose
D-mannoseD-Glucose
D isomer L isomer
Epimers
Enantiomers
Aldoses: Stereochemical RelationshipsCCHO
CH2OHH OH
CCHO
CH OH
CH2OHH OH
CCHO
CHO H
CH2OHH OH
D-Glyceraldehyde
D-Erythrose D-Threose
CC
CHO H
CH2OHH OH
CC
CHO H
CH2OHH OH
CC
CH OH
CH2OHH OH
CC
CH OH
CH2OHH OH
CHO CHO CHO CHOHO HH OHHO HH OH
D-Ribose (Rib) D-Arabinose (Ara) D-Xylose (Xyl) D-Lyxose (Lyx)
CC
CHO H
CH2OHH OH
CH OH
CC
CHO H
CH2OHH OH
CH OH
CC
CHO H
CH2OHH OH
CHO H
CC
CHO H
CH2OHH OH
CHO H
CC
CH OH
CH2OHH OH
CHO H
CC
CH OH
CH2OHH OH
CHO H
CC
CH OH
CH2OHH OH
CH OH
CC
CH OH
CH2OHH OH
CH OH
CHO CHOHOH OH
CHOCHOCHOCHOCHOCHOH HO H HO H HOH OH H OH H OH H
D-Allose D-Altrose D-Mannose (Man)
D-Gulose D-Idose D-Galactose (Gal)
D-TaloseD-Glucose (Glc)
Aldopentoses
Aldotetroses
Aldotriose
Aldohexoses
Ketoses: Stereochemical Relationships
• Ketoses have one less chiral center than their aldose counterparts.
• Ketoses have 2n-3 stereoisomers (n = number of carbon atoms).
• Ketoses with the carbonyl at the C2 position are most prevalent.
• Nomenclature: insert -ul- before the -ose ending in the name of the corresponding aldose.
CH2OHCCH2OH
O
Dihydroxyacetone
CCCH2OH
O
CH2OHH OH
D-Erythrulose
CCCH2OH
O
CH OH
CH2OHOHH
CCCH2OH
O
CHO H
CH2OHOHH
D-Ribulose D-Xylulose
CCCH2OH
O
CH OH
COHH
CH2OHOHH
CCCH2OH
O
CHO H
COHH
CH2OHOHH
CCCH2OH
O
CH OH
CHHO
CH2OHOHH
CCCH2OH
O
CHO H
CHHO
CH2OHOHH
D-Sorbose D-TagatoseD-Psicose D-Fructose
Configurations and Conformations• Aldehydes and ketones
can react with alcohols to form hemiacetals and hemiketals respectively.
• Aldehydes/ketones of monosaccharides can react with hydroxyl groups intramolecularly to form cyclic hemiacetals/hemiketals.
• Haworth projection formulas.!
CH2OHCCC
H OHH OH
HO HCH OHC
O H
OH
OH
CH2OH
HO
H
H
OH
OH
H1
2
3
4
5
6
61
2
34
5OH
HO
CH2OH
H
H
OH H
OHOH
H
CH2OHCCC
H OHH OH
HO HC OCH2OH
2
3
4
5
6
1
OH O CH2OHHOCH2
OHHH
OH
HO
H
HOCH2
HOH
OH
H
OCH2OH
D-Glucoseα-D-Glucopyranose
α-D-FructofuranoseD-Fructose
Cyclic Sugars• 6-membered rings:
pyranoses.• 5-membered rings:
furanoses.• Anomers differ in
configuration at the hemiacetal or hemiketal carbon.
• This carbon is called the anomeric carbon.!
• Anomers: α and β isomers.!
Pyran
Furan
O
O OH
HO
CH2OH
H
H
OH H
OHOH
H
O CH2OHHOCH2
OHHH
OH
HO
H
α-D-Glucopyranose
α-D-Fructoruranose
OH
HO
CH2OH
H
H
OH H
OHOH
H
α-D-Glucopyranose
anomeric carbon
OH
HO
CH2OH
H
H
OH H
OHH
OH
β-D-Glucopyranose
Anomers
Fischer -> Haworth• Haworth projections used to
represent cyclic saccharide structures.
• Substituents extend either above or below the ring.– Substituents on the left in a
Fischer projection are drawn above the ring.
– Substituents on the right in a Fischer projection are drawn below the ring.
– Exception: the carbon whose hydroxyl group forms the hemiacetal/hemiketal. !
– Remember α- and β-configurations. !
CH2OHCCC
H OHH OH
HO HCH OHC
O H
2
3
4
5
6
1
OH
HO
CH2OH
H
H
OH H
OHOH
H
CH2OHCCC
H OHH OH
HO HC OCH2OH
2
3
4
5
6
1
O CH2OHHOCH2
OHHH
OH
HO
H
D-Glucoseα-D-Glucopyranose
α-D-FructoruranoseD-Fructose
Fischer Projection Haworth Projection
Anomers and Interconversion• Anomers are defined based on the relative position of the
OH group on the anomeric carbon.!α - OH on the opposite side of the ring from the CH2OH.β - OH on the same side of the ring from the CH2OH.
• Monosaccharide anomers in solution interconvert readily.• Interconvesion proceeds via the linear form.!
OH
HO
CH2OH
H
H
OH H
OHOH
H
α-D-Glucopyranose
OH
HO
CH2OH
H
H
OH H
OHH
OH
β-D-GlucopyranoseCH2OHCH OHCH OHCHO HCH OHC
H O
D-Glucose
Conformational Variability• Pyranoses can assume
boat and chair conformations.
• Ring conformation effects chemical reactivity.– Equatorial OH
groups esterify more readily than axial OH groups.
• Furanose rings have similar conformational variability.
• Substituents influence conformational preferences.!
OH
HO
H
HO
H
HOHH OH
OH
O
OH
H
OH
H
OH
OHH
HH
HO
a
e
a
e
a
aea
e
e
ae
Possible chair confomrations for β-D-glucopyranose
Boat Chair
Pyranoses
Furanoses
Glycosidic Bonds
• Glycosidic bonds are formed by the condensation of the anomeric OH and another OH group (or in the case of nucleosides, N).
• Formation of glycosidic bonds is acid catalyzed.• Glycosidic bonds link sugar monomers in di- and
polysaccharides.!
OH
HO
CH2OH
H
H
OH H
OHOH
H
α-D-Glucopyranose
OH
HO
CH2OH
H
H
OH H
OHOCH3
H OH
HO
CH2OH
H
H
OH H
OHH
OCH3
+ CH3OHH+
Methyl−α-D-Glucoside Methyl−β-D-Glucoside
Oxidation and Reduction• Aldehydes of aldoses can be
oxidized to carboxylic acids under mild conditions (resulting in aldonic acids).
• Saccharides bearing anomeric carbons that are not involved in glycosidic bonds are called reducing sugars.
• Oxidation of the terminal primary alcohol to the carboxylic acid results in uronic acids.
• Both aldoses and ketoses can be reduced to their alcohols resulting in sugar alcohols.!
CH2OH
HO HH OHH OH
HO H
H O
D-Mannose
CH2OH
HO HH OHH OH
HO H
HO O
D-Mannic acid
CH2OH
HO HH OHH OH
HO HCH2OH
Mannitol
CO2H
HO HH OHH OH
HO H
H O
D-Mannuronic Acid
Oxidation Oxidation
Reduction
Sugar Derivatives• In deoxy sugars, an -OH
group has been replaced with and H.
• In amino sugars, one or more OH groups have been replaced with amino groups or acetylated amino groups.
• Amino sugars are common components in polysaccharides.!
O OHHOCH2
HHH
OH
H
OH
β-Ribose
O OHHOCH2
HHH
OH
H
H
β-2-Deoxyribose
OH
HO
CH2OH
H
H
OH H
OHOH
H
α-D-Glucose
OH
HO
CH2OH
H
H
OH H
NH2
OH
H
α-D-Glucosamine
OH
HO
CH2OH
H
H
OH H
HN
OH
H
N-Acetyl-α-D-Glucosamine
OCH3
Intro to Polysaccharides• Most carbohydrates in nature are
polysaccharides.• Have four characteristics:
– Identity of monosaccharide units– Length of chains– Types of bonds linking units– Degree of branching in chains
Polysaccharides!• Polysaccharides (glycans): monosaccharides linked
together by glycosidic bonds.• Homopolysaccharides are composed of one type of
monosaccharide.• Heteropolysaccharides are composed of more than
one type of monosaccharide. Their composition is usually repetitive.
• Polysaccharides are not limited to linear construction. They can be branched.
• Exoglycosidases and endoglycosidases: enzymes that cleave glycosidic bonds. !
Disaccharides!
• Disaccharides are two monosaccharides joined by an O-glycosidic bond.
• The reaction generally involves the anomeric carbon.
• They end with a free anomeric carbon is the reducing end.
• Few tri- or higher oligosaccharides.
O HHOCH2
CH2OHH
OH
HO
HGlucose Fructose
OH
HO
CH2OH
H
H
OH H
OH
H
Oα β1
2 3
1
2
3
Sucrose
OHO
H
CH2OH
H
H
OH H
OHH
OHCH2OH
H
H
OH H
OHOH
H
O
GlucoseGalactose
β1 4
Lactose
OH
HO
CH2OH
H
H
OH H
OH
H OHCH2OH
H
H
OH H
OHOH
H
Glucose
α1 4
Glucose
O
Maltose
Naming of Disaccharides• Anomeric configuration of left
monosaccharide is given first.• Nonreducing residue is named,
including furanosyl or pyranosyl.• The two carbons in the glycosidic
bond are identified: (1! 4), (1->6) etc.
• The second residue is named.– Sucrose : O-α-D-glucopyranosyl-(1-
>2)-β-D-fructofuranoside [note -ide ending].
– Lactose : O-β-D-galactopyranosyl-(1->4)-D-glucopyranose.
O HHOCH2
CH2OHH
OH
HO
HGlucose Fructose
OH
HO
CH2OH
H
H
OH H
OH
H
Oα β1
2 3
1
2
3
Sucrose
OHO
H
CH2OH
H
H
OH H
OHH
OHCH2OH
H
H
OH H
OHOH
H
O
GlucoseGalactose
β1 4
Lactose
OH
HO
CH2OH
H
H
OH H
OH
H OHCH2OH
H
H
OH H
OHOH
H
Glucose
α1 4
Glucose
O
Maltose
Polysaccharides!• Structural Polysaccharides:
Cellulose and Chitin.• Cellulose is the primary
component of plant cell walls. • Linear polymer of D-glucose.• Linkages, β(1->4).• Up to 15,000 saccharide
units.• Extensive interstrand
hydrogen bonding.• Accounts for almost half the
carbon in the biosphere.!
OHCH2OH
H
H
OH H
OHH
OHCH2OH
H
H
OH H
OHH
β1 4
Glucose
O
nGlucose
Cellulose
OHCH2OH
H
H
OH H
HNH
OHCH2OH
H
H
OH H
HNH
β1 4O O
n
N-Acetylglucosamine
Chitin
OCH3
OCH3
N-Acetylglucosamine
Structural Polysaccharides!• Structural Polysaccharides:
Cellulose and Chitin.• Chitin is the primary
component of invertebrate exoskeletons.
• Almost as abundant as cellulose.
• Linear homopolymer of N-acetyl-D-glucosamine.
• Linkages, β(1->4).• Structure is similar to that of
cellulose.
OHCH2OH
H
H
OH H
OHH
OHCH2OH
H
H
OH H
OHH
β1 4
Glucose
O
nGlucose
Cellulose
OHCH2OH
H
H
OH H
HNH
OHCH2OH
H
H
OH H
HNH
β1 4O O
n
N-Acetylglucosamine
Chitin
OCH3
OCH3
N-Acetylglucosamine
Storage Polysaccharides!• Starch: storage in plants.• Mixture of glycans:
– The linear homopolymer α-amylose (1->4).
– The branched homopolymer amylopectin (1->4) and (1->6).
– Amylopectin molecules can be as large as 106 glucose residues.
• Glycogen: storage in animals.– Resembles amylopectin.– More highly branched.!
OHCH2OH
H
H
OH H
OH
H OHCH2OH
H
H
OH H
OH
H
α1 4
Glucose
O
n
OHCH2OH
H
H
OH H
OH
H4
O Oα α1 1
OHCH2OH
H
H
OH H
OH
H OHCH2
H
H
OH H
OH
H
α1 4
Glucose
O
n
OHCH2OH
H
H
OH H
OH
H4
O Oα α1 1
OHCH2OH
H
H
OH H
HOO
H4
Oα1
6
α-Amylose (1->4 linkages)
OHCH2OH
H
H
OH H
OH
H4
Oα1
Amylopectin (1->4 linkages, 1->6 branches every 24-30 residues.)Glycogen (1->4 linkages, 1->6 branches every 8-12 residues.)
Glycosaminoglycans!• Glycosaminoglycans =
mucopolysaccharides.• Primary component of
ground substance, gel-like matrix.
• Extracellular spaces contain collagen and elastin fibres embedded in ground substance.
• Linear polysaccharides consisting of alternating uronic acid and hexosamine.
• Solutions are viscous and demonstrate elasticity.!
OH
HO
CH2OH
H
H
H
HNH
4β1
OHCO2
-
H
H
OH H
OHH
4O β
1
D-Glucuronate
N-Acetyl-D-glucosamine
O O
OCH3
Hyaluronate (hyaluronan)
O-O3SO
H
CH2OH
H
H
H
HNH
4β1
OHCO2
-
H
H
OH H
OHH
4O β
1
D-Glucuronate
N-Acetyl-D-galactosamine-4-sulfate
O O
OCH3
Chondroitin-4-sulfateComponent of cartiledge and connective tissues
Important component of ground substance, synovial fluid and vitrious humor of the eye. (also in bacterial capsules)
OHH
CO2-
H
OH H
OSO3-
H
OHCH2OSO3
-
H
H
OH H
NHOSO3-
H
α1 4O
Oα
L-Iduronate-2-sulfate
N-Sulfo-D-glucosamine-6-sulfate
HeparinVariably sulfated, most negaive polyelectrolyte in mammalian tissues. Inhibits blood clotting.