Carbohydrates
Carbohydrates
• Most abundant class of biological
molecules on Earth
• Originally produced through CO2
fixation during photosynthesis
Roles of Carbohydrates
• Energy storage (glycogen,starch)
• Structural components
(cellulose,chitin)
• Cellular recognition
• Carbohydrate derivatives include
DNA, RNA, co-factors,
glycoproteins, glycolipids
Carbohydrates
• Monosaccharides (simple sugars)
cannot be broken down into simpler
sugars under mild conditions
• Oligosaccharides = "a few" - usually
2 to 10
• Polysaccharides are polymers of the
simple sugars
Monosaccharides
• Polyhydroxy ketones (ketoses)
and aldehydes (aldoses)
• Aldoses and ketoses contain
aldehyde and ketone
functions, respectively
• Ketose named for “equivalent
aldose” + “ul” inserted
• Triose, tetrose, etc. denotes
number of carbons
• Empirical formula = (CH2O)n
O
H
C
CH2OH
H
C*
OH
HO
C*
H
H
C*
OH
CH2OH
D-ribose
C
O
HO
C*
H
H
C*
OH
CH2OH
D-ribulose
Monosaccharides are chiral
• Aldoses with 3C or more and
ketoses with 4C or more are
chiral
• The number of chiral carbons
present in a ketose is always
one less than the number
found in the same length
aldose
• Number of possible
steroisomers = 2n (n = the
number of chiral carbons)
O
H
C
CH2OH
H
C*
OH
HO
C*
H
H
C*
H
C*
C
O
HO
C*
H
OH
H
C*
OH
OH
H
C*
OH
CH2OH
CH2OH
D-glucose
D-fructose
Stereochemistry
Enantiomers
O
H
O
C
O
H
C
HO
C*
H
H
C*
OH
HO
C*
HO
C*
Epimers
Diastereomers
O
H
C
C
C*
OH
HO
C*
H
H
C*
OH
HO
C*
H
HO
C*
H
HO
C*
H
H
C*
OH
H
C*
OH
HO
H
H
C*
OH
H
C*
OH
H
CH2OH
L-glucose
D-glucose
O
H
C
H
CH2OH
O
H
H
C
H
C*
OH
HO
C*
H
H
HO
C*
H
HO
C*
H
C*
H
H
C*
OH
H
C*
OH
C*
OH
H
C*
OH
H
C*
OH
CH2OH
CH2OH
D-mannose
D-galactose
CH2OH
D-glucose
CH2OH
D-mannose
•Enantiomers = mirror images
•Pairs of isomers that have opposite configurations at
one or more chiral centers but are NOT mirror images
are diastereomers
•Epimers = Two sugars that differ in configuration at
only one chiral center
Cyclization of aldose and ketoses
introduces additional chiral center
• Aldose sugars (glucose) can cyclize to form a
H
cyclic hemiacetal H
NEW CHIRAL
ALDEHYDE
O
O
C
H
ALCOHOL
H
R1
C*
R1
O
R2
O
H
CARBON
R2
HEMIACETAL
• Ketose sugars (fructose) can cyclize to form a
H
H
cyclic hemiketal
NEW CHIRAL
KETONE
O
O
CARBON
C
R
ALCOHOL
R
R1
R1
O
R2
O
H
C*
R2
HEMIKETAL
Glucopyranose formation
Fructofuranose formation
Monosaccharides can cyclize to
form Pyranose / Furanose forms
a = 64%
b = 36%
a = 21.5%
b = 58.5%
a = 13.5%
b = 6.5%
Haworth Projections
O
H
-OH up = beta
-OH down = alpha
C1
H
C2
OH
HO
C3
H
H
C4
OH
H
C5
OH
CH2OH
6
5
4
1
3
2
Anomeric carbon
(most oxidized)
For all non-anomeric carbons, -OH groups
point down in Haworth projections if
pointing right in Fischer projections
Conformation of Monosaccharides
Pyranose sugars not planar molecules, prefer to be in
either of the two chair conformations.
Reducing Sugars
• When in the uncyclized
form, monosaccharides
act as reducing agents.
• Free carbonyl group from
aldoses or ketoses can
reduce Cu2+ and Ag+ ions
to insoluble products
Derivatives of
Monosaccharides
Sugar Phosphates
Deoxy Acids
Amino Sugars
Sugar alcohols
Monosaccharide structures
you need to know
1)
2)
3)
4)
5)
6)
Glucose
Fructose
Ribose
Ribulose
Galactose
Glyceraldehyde
Carbohydrates
• Monosaccharides (simple sugars)
cannot be broken down into simpler
sugars under mild conditions
• Oligosaccharides = "a few" - usually
2 to 10
• Polysaccharides are polymers of the
simple sugars
CH2OH
Glycosidic
Linkage
CH2OH
hemiacetal
O
O
OH
OH
OH
OH
OH
OH
alcohol
OH
Hydrolysis
H 2O
H 2O
Condensation
CH2OH
O
CH2OH
acetal
OH
O
OH
OH
O
OH
OH
OH
glycosidic linkage
OH
Disaccharides
CH2OH
H
CH2OH
O H
OH
H
H
O
OH
OH
maltose
H
H
H
OH
H
O
OH
O H
OH
H
H
OH
lactose
H
CH2OH
OH
H
OH
O
sucrose
OH
OH
CH2OH
O
H
OH
H
CH2OH
OH
CH2OH
H
O OH
OH
O
H
O
H
H
H
H
H
OH
(b-D-glucosyl-(1->4)-b-D-glucopyranose)
CH2OH
H
H
H
OH
H
H
O
OH
(a-D-glucosyl-(1->4)-b-D-glucopyranose)
O OH
OH
H
OH
H
CH2OH
O
cellobiose
CH2OH
OH
H
OH
(b-D-galactosyl-(1->4)-b-D-glucopyranose)
H
(a-D-glucosyl-(1->2)-b-D-fructofuranose)
Higher Oligosaccharides
Oligosaccharide groups are incorporated
in to many drug structures
Polysaccharides
• Nomenclature: homopolysaccharide vs.
heteropolysaccharide
• Starch and glycogen are storage
molecules
• Chitin and cellulose are structural
molecules
• Cell surface polysaccharides are
recognition molecules
Starch
• A plant storage polysaccharide
• Two forms: amylose and amylopectin
• Most starch is 10-30% amylose and 70-90%
amylopectin
• Average amylose chain length 100 to 1000
residues
• Branches in amylopectin every 25 residues (1525 residues) a-1->6 linkages
• Amylose has a-1->4 links, one reducing end
Amylose and Amylopectin
Starch
• Amylose is poorly
soluble in water,
but forms micellar
suspensions
• In these
suspensions,
amylose is helical
Glycogen
• Storage polysaccharide in animals
• Glycogen constitutes up to 10% of liver mass
and 1-2% of muscle mass
• Glycogen is stored energy for the organism
• Only difference from starch: number of
branches
• Alpha(1,6) branches every 8-12 residues
• Like amylopectin, glycogen gives a red-violet
color with iodine
Dextrans
• If you change the main linkages between
glucose from alpha(1,4) to alpha(1,6), you get a
new family of polysaccharides - dextrans
• Branches can be (1,2), (1,3), or (1,4)
• Dextrans formed by bacteria are components of
dental plaque
• Cross-linked dextrans are used as "Sephadex"
gels in column chromatography
• These gels are up to 98% water!
Dextrans
Cellulose
• Cellulose is the most abundant
natural polymer on earth
• Cellulose is the principal strength
and support of trees and plants
• Cellulose can also be soft and
fuzzy - in cotton
Cellulose vs Amylose
amylose
cellulose
Glucose units rotated 180o relative to next residue
Cellulose
• Beta(1,4) linkages make all the difference!
• Strands of cellulose form extended ribbons
• Interchain H-bonding allows multi-chain
interactions. Forms cable like structures.
Chitin
• exoskeletons of crustaceans, insects and
spiders, and cell walls of fungi
• similar to cellulose, but instead of glucose
uses N-acetyl glucosamine (C-2s are Nacetyl instead of –OH)
 b-1->4 linked N-acetylglucosamine units
• cellulose strands are parallel, chitins can
be parallell or antiparallel
CH2OH
OH
OH
O
OH
H
H
H
H
NH
C
CH3
O
Chitin vs Cellulose
Peptidoglycan
• N-acetylglucosamine and
N-acetylmuramic acid
groups linked b-1->4
• Heteroglycan linked to a
tetrtapeptide (AlaIsoGlu-Lys-Ala)
• Gram (-) have petantaglycine linker to next
strand
• Gram (+) have directly
cross links to next
strand
Peptidoglycan
Peptidoglycan is target of
antibacterial agents
•Lysozyme = enzyme that cleaves polysaccharide
chain of peptidoglycan
•Penicillin = inhibits linking of peptidoglycan chains.
•Inhibits bond formation between terminal alanine
and pentaglycine linker
•Penicillian looks like an Ala-Ala
Peptidoglycan and Bacterial Cell Walls
Composed of 1 or 2 bilayers and peptidoglycan shell
• Gram-positive: One bilayer and thick
peptidoglycan outer shell
• Gram-negative: Two bilayers with thin
peptidoglycan shell in between
• Gram-positive: pentaglycine bridge connects
tetrapeptides
• Gram-negative: direct amide bond between
tetrapeptides
Glycoproteins
• May be N-linked or O-linked
• N-linked saccharides are
attached via the amide nitrogens
of asparagine residues
• O-linked saccharides are
attached to hydroxyl groups of
serine, threonine or hydroxylysine
O-linked Glycoproteins
• Function in many cases is to
adopt an extended conformation
• These extended conformations
resemble "bristle brushes"
• Bristle brush structure extends
functional domains up from
membrane surface
O-linked Glycoproteins
N-linked Glycoproteins
• Oligosaccharides can alter the chemical and
physical properties of proteins
• Oligosaccharides can stabilize protein
conformations and/or protect against proteolysis
• Cleavage of monosaccharide units from N-linked
glycoproteins in blood targets them for
degradation in the liver
• Involved in targeting proteins to specific
subcellular compartments