Download Carbohydrates

Carbohydrates (glycans) have the following
basic composition:
(CH2O)n
I
or H - C - OH
I
 Monosaccharides - simple sugars with multiple OH
groups. Based on number of carbons (3, 4, 5, 6), a
monosaccharide is a triose, tetrose, pentose or hexose.
 Disaccharides - 2 monosaccharides covalently linked.
 Oligosaccharides - a few monosaccharides covalently
linked.
 Polysaccharides - polymers consisting of chains of
monosaccharide or disaccharide units.
Monosaccharides
Aldoses (e.g., glucose) have
Ketoses (e.g., fructose) have
an aldehyde group at one end. a keto group, usually at C2.
H
O
CH2OH
C
C
O
HO
C
H
OH
H
C
OH
OH
H
C
OH
H
C
OH
HO
C
H
H
C
H
C
CH2OH
CH2OH
D-glucose
D-fructose
D vs L Designation
CHO
CHO
D & L designations
are based on the
configuration about
the single asymmetric
C in glyceraldehyde.
H
C
OH
HO
L-glyceraldehyde
CHO
The lower
representations are
Fischer Projections.
H
C
OH
CH2OH
D-glyceraldehyde
H
CH2OH
CH2OH
D-glyceraldehyde
C
CHO
HO
C
H
CH2OH
L-glyceraldehyde
Sugar Nomenclature
For sugars with more
than one chiral center,
D or L refers to the
asymmetric C farthest
from the aldehyde or
keto group.
Most naturally occurring
sugars are D isomers.
O
H
C
H – C – OH
HO – C – H
H – C – OH
H – C – OH
CH2OH
D-glucose
O
H
C
HO – C – H
H – C – OH
HO – C – H
HO – C – H
CH2OH
L-glucose
D & L sugars are mirror
images of one another.
They have the same
name, e.g., D-glucose
& L-glucose.
Other stereoisomers
have unique names,
e.g., glucose, mannose,
galactose, etc.
O
H
C
H – C – OH
HO – C – H
H – C – OH
H – C – OH
CH2OH
D-glucose
O
H
C
HO – C – H
H – C – OH
HO – C – H
HO – C – H
CH2OH
L-glucose
The number of stereoisomers is 2n, where n is the
number of asymmetric centers.
The 6-C aldoses have 4 asymmetric centers. Thus there
are 16 stereoisomers (8 D-sugars and 8 L-sugars).
Hemiacetal & hemiketal formation
R'
An aldehyde can R' O
H
react with an
alcohol to form
a hemiacetal. alcohol
A ketone can
react with an
alcohol to form
a hemiketal.
R
R
O
C O
H
R
H
alcohol
H
hemiacetal (C-O-C-O-H)
aldehyde
O
O
H
R'
R'
C
C O
R''
R
O
C
O
H
R''
ketone
hemiketal (C-O-C-O-H)
Ring Closure in
glucose…hemiacetal formation
O
CH2OH
H
OH
CH2OH
O
HO
OH
CH2OH
O
C
OH
OH
OH
O
OH
OH
OH
OH
OH
From Fischer to Haworth
• OH on the right appear below the ring
• OH on left appear above ring
Ring Closure in
Fructose…hemiketal formation
CH2OH
C O
H
CH2OH
HO
CH2OH
O
OH
C OH
CH2OH
C
HO
OH
C
O
CH2OH
CH2OH
O
C
C
HO
OH
OH
Anomers
• Anomeric carbon is carbonyl carbon
• Depending on orientation during
nucleophilic attack, can get two orientations
• If ring closes with OH below ring, then is
called α
• If ring closes with OH above ring, then is
called β
Anomer formation in glucose
H
O
CH2OH
H
OH
O
HO
O
C
OH
OH
CH2OH
H
OH
OH
O
OH
OH
OH
CH2OH
H
OH
OH
alpha glucose
H
O
CH2OH
H
OH
O
HO
CH2OH
CH2OH
O
C
OH
OH
O
OH
OH
H
OH
OH
OH
OH
H
OH
beta glucose
Draw the following in the closed
form… do the first as α galactose
an the second as β ribose
H
O
OH
HO
H
HO
H
H
OH
CH2OH
galactose
H
O
OH
H
OH
H
OH
CH2OH
ribose
Answers
HO
CH2OH
O
OH
OH
OH
alpha galactose
CH2OH
OH
OH
O
OH
beta ribose
Sugar derivatives
CHO
COOH
CH2OH
H
C
OH
H
C
OH
H
C
OH
CH2OH
D-ribitol
H
C
OH
HO
C
H
OH
H
C
OH
OH
H
C
OH
H
C
OH
HO
C
H
H
C
H
C
CH2OH
D-gluconic acid
COOH
D-glucuronic acid
 sugar alcohol - lacks an aldehyde or ketone; e.g., ribitol.
 sugar acid - the aldehyde at C1, or OH at C6, is oxidized
to a carboxylic acid; e.g., gluconic acid, glucuronic acid.
Sugar derivatives
CH2OH
CH2OH
O
H
H
OH
H
H
OH
H
OH
OH
H
NH2
-D-glucosamine
O
H
H
H
O OH
OH
H
N
C
CH3
H
-D-N-acetylglucosamine
amino sugar - an amino group substitutes for a hydroxyl.
An example is glucosamine.
The amino group may be acetylated, as in
N-acetylglucosamine.
H
O
H3C
C
O
NH
R
H
COO
H
R=
OH
H
HC
OH
HC
OH
CH2OH
OH
H
N-acetylneuraminate (sialic acid)
N-acetylneuraminate (N-acetylneuraminic acid, also
called sialic acid) is often found as a terminal residue
of oligosaccharide chains of glycoproteins.
Sialic acid imparts negative charge to glycoproteins,
because its carboxyl group tends to dissociate a proton
at physiological pH, as shown here.
Reducing Sugars
• Sugars that contain aldehyde groups that are oxidized to
carboxylic acids are classified as reducing sugars.
• Common test reagents are :
• Benedicts reagent (CuSO4 / citrate)
• Fehlings reagent (CuSO4 / tartrate)
• They are classified as reducing sugars since they
reduce the Cu2+ to Cu+ which forms as a red
precipitate, copper (I) oxide.
• So any sugar that contains a hemi-acetal will be a
reducing sugar.
Hemiacetals are reducing sugars
• In equilibrium with the aldehyde
O
OH
HO
CH2OH
O
OH
OH
OH
CH2OH
OH
OH
OH
Are hemiketals reducing?
• What are they in equilibrium with?
• Is this oxidizable?
Fructose, however is reducing
CH2OH
C O
HO C
CHOH
H
C OH
HO C
O
C
C OH
HO C
OH
OH
OH
OH
OH
CH2OH
OH
CH2OH
CH2OH
fructose
ene-diol intermediate
glucose
Acetal/ketal Formation
R'O
R''
O
H
R'O
H
H
C
R''O
OH
R
C
+
H2O
R
hemiacetal
alcohol
R'O
R'''
O
H
R'O
R''
R''
C
R
acetal
OH
R'''O
C
R
alcohol
hemiketal
Ketal
+
H2O
Glycosidic Bonds
Acetal or ketal linkage between sugars
CH2OH
O
CH2OH
H
O
OH
OH
O
C
OH
hemiacetal
OH
H
OH
OH
OH
O
O
+
OH
OH
OH
alcohol
CH2OH
CH2OH
O
OH
acetal
OH
OH
H2O
Disaccharide nomenclature
• Sugars named
• Linkages named as to from what carbon on sugar
1 to what carbon on sugar 2
• Anomeric carbon has to be specified as α or β
• Next slide has glucose-glucose in an α 1,4 linkage
– Carbon 1 is α and attaches to carbon 4 on the next
glucose
• Also shown is β 1,4 linkage
– Carbon 1 is β and attaches to carbon 4 on the next
glucose
Disaccharides:
Maltose, a cleavage
product of starch
(e.g., amylose), is a
disaccharide with an
(1 4) glycosidic
link between C1 - C4
OH of 2 glucoses.
It is the  anomer
(C1 O points down).
CH2OH
CH2OH
O
O
OH
OH
OH
OH
O
OH
OH
alpha 1,4 glucose-glucose (maltose)
CH2OH
O
CH2OH
O
OH
OH
OH
O
OH
OH
OH
beta-1,4-glucose-glucose (cellobiose
Cellobiose, a product of cellulose breakdown, is the
otherwise equivalent b anomer (O on C1 points up).
The b(1 4) glycosidic linkage is represented as a zig-zag,
but one glucose is actually flipped over relative to the other.
Draw the following
• Glucose-glucose in an α-1,6 linkage
• Glucose-galactose in an α-1, β -1 linkage
– (glucose is alpha and galactose in beta)
Answers
CH2OH
O
• Glucose-glucose in
α 1,6 linkage
OH
HO
O
OH
CH2
O
OH
OH
HO
• Glucose α -1 –
galactose β - 1
OH
CH2OH
O
OH
OH
O
O
OH
CH2OH
OH
OH
OH
Other disaccharides include:
 Sucrose, common table sugar, has a glycosidic bond
linking the anomeric hydroxyls of glucose & fructose.
Because the configuration at the anomeric C of glucose
is  (O points down from ring), the linkage is (12).
 Lactose, milk sugar, is composed of galactose &
glucose, with b(14) linkage from the anomeric OH of
galactose. Its full name is b-D-galactopyranosyl-(1 4)-D-glucopyranose
Sucrose
Lactose
Lactose Intolerance
• Lactose or milk sugar occurs in the milk of mammals - 46% in cow's milk and 5-8% in human milk. It is also a by
product in the the manufacture of cheese.
• Lactose intolerance is the inability to digest significant
amounts of lactose, the predominant sugar of milk. This
inability results from a shortage of the enzyme lactase,
which is normally produced by the cells that line the small
intestine. Lactase breaks down the lactose, milk sugar, into
glucose and galactose that can then be absorbed into the
bloodstream.
Polysaccharides
CH2OH
H
O
H
OH
H
H
H
1
O
OH
6CH OH
2
5
O
H
4 OH
3
H
OH
H
H
H
H 1
O
H
OH
CH2OH
CH2OH
CH2OH
H
H
H
O
H
OH
H
O
O
H
H
O
H
OH
H
O
OH
2
OH
H
OH
H
OH
H
H
OH
amylose
Plants store glucose as amylose or amylopectin, glucose
polymers collectively called starch. Glucose storage in
polymeric form minimizes osmotic effects.
Amylose is a glucose polymer with (14) linkages. It
adopts a helical conformation.
The end of the polysaccharide with an anomeric C1 not
involved in a glycosidic bond is called the reducing end.
CH2OH
CH2OH
O
H
H
OH
H
H
OH
H
O
OH
CH2OH
H
H
OH
H
H
OH
H
H
OH
CH2OH
O
H
OH
O
H
OH
H
H
O
O
H
OH
H
H
OH
H
H
O
4
amylopectin
H
1
O
6 CH2
5
H
OH
3
H
CH2OH
O
H
2
OH
H
H
1
O
CH2OH
O
H
4 OH
H
H
H
H
O
OH
O
H
OH
H
H
OH
H
OH
Amylopectin is a glucose polymer with mainly (14)
linkages, but it also has branches formed by (16)
linkages. Branches are generally longer than shown above.
The branches produce a compact structure & provide
multiple chain ends at which enzymatic cleavage can occur.
CH2OH
CH2OH
O
H
H
OH
H
H
OH
H
O
OH
CH2OH
H
H
OH
H
H
OH
H
H
OH
CH2OH
O
H
OH
O
H
OH
H
H
O
O
H
OH
H
H
OH
H
H
O
4
glycogen
H
1
O
6 CH2
5
H
OH
3
H
CH2OH
O
H
2
OH
H
H
1
O
CH2OH
O
H
4 OH
H
H
H
H
O
OH
O
H
OH
H
H
OH
H
OH
Glycogen, the glucose storage polymer in animals, is
similar in structure to amylopectin. But glycogen has
more (16) branches.
The highly branched structure permits rapid release of
glucose from glycogen stores, e.g., in muscle during
exercise. The ability to rapidly mobilize glucose is more
essential to animals than to plants.
Review quiz
• Which hormone signals the release of
glycogen into glucose?
• What was the mechanism of signal
transduction?
CH2OH
O
CH2OH
O
OH
CH2OH
O
CH2OH
O
OH
CH2OH
O
CH2OH
O
OH
OH
O
O
OH
OH
O
OH
OH
OH
O
OH
OH
OH
O
OH
OH
Cellulose, a major constituent of plant cell walls, consists
of long linear chains of glucose with b(14) linkages.
.
1. How does the structure in cellulose affects it bonding?
2. Animals lack the enzymes needed to break down these
linkages. How do animals, like cattle, subsist on
cellulose?
Answer 1
• The van der Waals interactions cause cellulose
chains to be straight & rigid, and pack with a
crystalline arrangement in thick bundles called
microfibrils
• The role of cellulose is to impart strength and
rigidity to plant cell walls, which can withstand
high hydrostatic pressure gradients. Osmotic
swelling is prevented.
Answer 2
• Animals, like cattle, have commensal
bacteria in their gut that can break the
linkages of cellulose.
Chitin
CH2OH
O
O
OH
CH2OH
•Similar to cellulose
b(14) linkages.
O
O
OH
CH2OH
O
O
OH
OH
NH
C CH3
NH
C CH3
O
NH
C CH3
O
O
•The monomer is N-acetyl-bD-glucosamine
•Plays a structural role
•Structural components of exoskeleton of
invertebrates
C
CH2OH
Oligosaccharides
that are covalently
attached to proteins
or to membrane
lipids may be linear
or branched chains.
O
H
H
OH
O
CH2
CH
NH
H
O
serine
residue
O H
OH
H
HN
C
CH3
b-D-N-acetylglucosamine
O-linked oligosaccharide chains of glycoproteins vary
in complexity.
They link to a protein via a glycosidic bond between a
sugar residue & a serine or threonine OH.
O-linked oligosaccharides have roles in recognition,
interaction, and enzyme regulation.
C
CH2OH
O
H
H
OH
O
CH2
CH
NH
H
O
serine
residue
O H
OH
H
HN
C
CH3
b-D-N-acetylglucosamine
•N-acetylglucosamine (GlcNAc) is a common O-linked
glycosylation of protein serine or threonine residues.
•Many cellular proteins, including enzymes & transcription factors,
are regulated by reversible GlcNAc attachment.
•Often attachment of GlcNAc to a protein OH alternates with
phosphorylation, with these 2 modifications having opposite
regulatory effects (stimulation or inhibition).
CH2OH
O
O
H
H
OH
HN
C
HN
CH2
C
H
H
OH
H
HN
C
CH3
O
N-acetylglucosamine
Initial sugar in N-linked
glycoprotein oligosaccharide
Asn
CH
O
HN
HC
R
C
O
X
HN
HC
R
C
O
Ser or Thr
N-linked oligosaccharides of glycoproteins tend to be
complex and branched. First N-acetylglucosamine is
linked to a protein via the side-chain N of an asparagine
residue in a particular 3-amino acid sequence.
Many proteins secreted by cells have attached
N-linked oligosaccharide chains.
Carbohydrate chains of plasma membrane
glycoproteins and glycolipids usually face the
outside of the cell.
They have roles in cell-cell interaction and
signaling, and in forming a protective layer on the
surface of some cells.