Contributed by:
The highlights are:
• structures of some important monosaccharides
• structures and properties of disaccharides
• structures and biological roles of polysaccharides
• functions of glycosaminoglycans as structural components of the extracellular matrix
• functions glycoconjugates in regulating a variety of biological functions
1.
7 | Carbohydrates and
Glycobiology
© 2017 W. H. Freeman and Company
2.
Energy storage Structural materials
and more….
Carbohydrates are the most abundant biological molecule.
(C·H2O)n (n≥3)
Chapter 8 Opener
3.
Carbohydrates
• Named so because many have formula Cn(H2O)n
• Produced from CO2 and H2O via photosynthesis in plants
• Range from as small as glyceraldehyde (Mw = 90 g/mol) to as
large as amylopectin (Mw > 200,000,000 g/mol)
• Fulfill a variety of functions, including:
– energy source and energy storage
– structural component of cell walls and exoskeletons
– informational molecules in cell-cell signaling
• Can be covalently linked with proteins and lipids
4.
Carbohydrates
• Basic nomenclature:
– number of carbon atoms in the carbohydrate + -ose
– example: three carbons = triose
• Common functional groups:
– All carbohydrates initially had a carbonyl functional
group.
– aldehydes = aldose
– ketones = ketose
5.
Carbohydrates Can Be Constitutional Isomers
• An aldose is a carbohydrate with aldehyde functionality.
• A ketose is a carbohydrate with ketone functionality.
6.
Enantiomers Are Mirror Images
7.
Carbohydrates Can Be Stereoisomers
• Enantiomers
– stereoisomers that are nonsuperimposable mirror images
• In sugars that contain many chiral centers, only the one
that is most distant from the carbonyl carbon is
designated as d (right) or l (left).
• d and l isomers of a sugar are enantiomers.
– For example, l- and d-glucose have the same water solubility.
• Most hexoses in living organisms are d stereoisomers.
• Some simple sugars occur in the l form, such as
l-arabinose.
8.
Drawing Monosaccharides
• Chiral compounds can be
drawn using perspective
formulas.
• However, chiral
carbohydrates are usually
represented by Fischer
projections.
• Horizontal bonds are
pointing toward you;
vertical bonds are
projecting away from you.
9.
Carbohydrates Can Be Stereoisomers
• Epimers are stereoisomers that differ at only one chiral center.
• Epimers are NOT mirror images, and therefore are NOT
enantiomers.
• Epimers are diastereomers; diastereomers have different
physical properties (i.e., water solubility, melting temp).
• example: D-Threose is the C-2 epimer of D-erythrose.
• Both are D sugars because they both have the same
orientation around the last chiral carbon in the chain.
10.
Diastereomers
• Diastereomers: stereoisomers that are not mirror
images
• Diastereomers have different physical properties.
– For example, water solubilities of threose and erythrose are
different.
11.
Epimers
• D-Mannose and D-galactose are both epimers of
D-glucose.
• D-Mannose and D-galactose vary at more than one
chiral center and are diastereomers, but not epimers.
12.
Common Carbohydrates
in Biochemistry
• Ribose is the standard five-carbon sugar.
• Glucose is the standard six-carbon sugar.
• Galactose is an epimer of glucose.
• Mannose is an epimer of glucose.
• Fructose is the ketose form of glucose.
16.
The D-aldoses with up to six carbon atoms
D sugars have the same
absolute configuration at the
asymmetric center farthest
from their carbonyl group.
Figure 8-1
17.
D sugars
2n-2 possible
CHO CHO stereoisomers
HOCH HCOH
Here, n = 4,
HOCH L sugars HOCH so there are 4 stereoisomers
CH2OH CH2OH
L-Erythrose L-Threose
Figure 8-1 part 1
18.
Ribose is the most common aldo-pentose
Figure 8-1 part 2
19.
Glucose and mannose are “epimers”, as they differ by at only one chiral center.
Figure 8-1 part 3
20.
Carbon atom number in D-glucose:
2n-2 possible
stereoisomers,
as C1 and C6 are
not chiral centers.
Page 221
21.
The D-ketoses up to six carbon atoms
Only 2n-3 possible stereoisomers,
as there is one less stereo center
as compared to the aldoses.
Figure 8-2
22.
These ketoses will be seen again
when we cover to metabolism.
Figure 8-2
23.
Reactivity of Carbohydrates: Hemiacetals and
Hemiketals
• Aldehyde and ketone carbons are electrophilic.
• Alcohol oxygen atom is nucleophilic.
• When aldehydes are attacked by alcohols, hemiacetals form.
• When ketones are attacked by alcohols, hemiketals form.
• These reactions form the basis of cyclization of sugars.
24.
Be sure to know this!
Page 221
25.
Cyclization of
• The nucleophilic alcohol attacks
the electrophilic carbonyl
carbon, allowing formation of a
hemiacetal.
• As a result, the linear
carbohydrate forms a ring
structure.
• At the completion of this
structure, the carbonyl carbon is
reduced to an alcohol
• The orientation of the alcohol
around the carbon is variable
and transient.
26.
The interconversion of D-glucopyranose between
its and forms.
C1 is the called anomeric carbon, hence, each sugar
has two “anomers”, the and anomers.
Figure 8-4
27.
Cyclization of Monosaccharides
• Pentoses and hexoses readily undergo intramolecular
cyclization.
• The former carbonyl carbon becomes a new chiral
center, called the anomeric carbon.
– When the former carbonyl oxygen becomes a hydroxyl group,
the position of this group determines if the anomer is or .
– If the hydroxyl group is on the opposite side (trans) of the ring
as the CH2OH moiety, the configuration is .
– If the hydroxyl group is on the same side (cis) of the ring as
the CH2OH moiety, the configuration is .
28.
Cyclization of Monosaccharides:
Pyranoses and Furanoses
• Six-membered oxygen-containing rings are called
pyranoses after the pyran ring structure.
• Five-membered oxygen-containing rings are called
furanoses after the furan ring structure.
• The anomeric carbon is usually drawn on the right
side.
30.
Conformational Formulas of Cyclized
Monosaccharides
• Cyclohexane rings have “chair” or “boat” conformations.
• Pyranose rings favor “chair” conformations.
• Multiple “chair” conformations are possible but require energy
for interconversion (~46 kJ/mole).
31.
Two chair conformation of -D-glucopyranose
Less crowding with bulky More crowding with bulky
OH and CH2OH groups in OH and CH2OH groups in
the equitorial positions the axial positions
Dominant form in solution.
Only -D-glucose can simultaneously have
all five non-H substituents in equatorial positions.
Figure 8-5
32.
Important Hexose Derivatives
33.
Often seen along with table sugar:
Box 8-2a
34.
Also seen at the table, and in diet sodas:
Box 8-2b
35.
Sometimes used with aspartame, acts synergistically to make both
compounds sweeter.
Box 8-2c
36.
Still room for improvement…
Since 1879
Carcinogen ?
Since 1981
Causes cancer in rats in
VERY high dosages.
(problem for phenylketonuria)
37.
Reducing Sugars
• Reducing sugars have a free anomeric carbon.
– Aldehyde can reduce Cu2+ to Cu+ (Fehling’s test).
– Aldehyde can reduce Ag+ to Ag0 (Tollens’ test).
– It allows detection of reducing sugars, such as glucose.
– Modern detection techniques use colorimetric and
electrochemical tests.
38.
Colorimetric Glucose Analysis
-D-Gluconolactone
• Enzymatic methods are used to
-D-Glucose
quantify reducing sugars such as
CH2OH CH2OH
glucose.
O OH O
Glucose oxidase
OH OH O – The enzyme glucose oxidase
HO HO catalyzes the conversion of glucose
OH O2 OH
to glucono--lactone and hydrogen
peroxide.
H2O2
NH – Hydrogen peroxide oxidizes organic
OCH3 NH2
OCH3
molecules into highly colored
2 H2O
compounds.
– Concentrations of such compounds
Peroxidase
is measured colorimetrically.
OCH3
NH OCH3
NH2
Oxidized Reduced • Electrochemical detection is
o-dianisidine o-dianisidine
(bright orange) (faint orange) used in portable glucose
sensors.
39.
The Glycosidic Bond
• Two sugar molecules can be joined via a glycosidic bond between an
anomeric carbon and a hydroxyl carbon.
• The glycosidic bond (an acetal) between monomers is more stable and
less reactive than the hemiacetal at the second monomer.
– The second monomer, with the hemiacetal, is reducing.
– The anomeric carbon involved in the glycosidic linkage is nonreducing.
• Disacharides can be named by the organization and linkage or a
common name.
– The disaccharide formed upon condensation of two glucose molecules via a
1 4 bond is described as α-D-glucopyranosyl-(14)-D-glucopyranose.
– The common name for this disaccharide is maltose.
41.
Nonreducing Disaccharides
• Two sugar molecules can be
also joined via a glycosidic
bond between two anomeric
carbons.
• The product has two acetal
groups and no hemiacetals.
• There are no reducing ends;
this is a nonreducing sugar.
42.
Polysaccharides
• Natural carbohydrates are usually found as polymers.
• These polysaccharides can be:
– homopolysaccharides (one monomer unit)
– heteropolysaccharides (multiple monomer units)
– linear (one type of glycosidic bond)
– branched (multiple types of glycosidic bonds)
• Polysaccharides do not have a defined molecular weight.
– This is in contrast to proteins because, unlike proteins, no
template is used to make polysaccharides.
– Polysaccharides are often in a state of flux; monomer
units are added and removed as needed by the organism.
44.
Homopolymers of Glucose:
Glycogen
• Glycogen is a branched homopolysaccharide of
glucose.
– Glucose monomers form (1 4) linked chains.
– There are branch points with (1 6) linkers every
8–12 residues.
– Molecular weight reaches several millions.
– It functions as the main storage polysaccharide in
animals.
45.
Homopolymers of Glucose:
Starch
• Starch is a mixture of two homopolysaccharides of
glucose.
• Amylose is an unbranched polymer of (1 4)
linked residues.
• Amylopectin is branched like glycogen, but the
branch points with (1 6) linkers occur every 24–
30 residues.
• Molecular weight of amylopectin is up to 200
million.
• Starch is the main storage polysaccharide in plants.
46.
Glycosidic Linkages in Glycogen and Starch
47.
Mixture of Amylose and
Amylopectin in Starch
48.
Metabolism of Glycogen and Starch
• Glycogen and starch are insoluble due to their high
molecular weight and often form granules in cells.
• Granules contain enzymes that synthesize and degrade
these polymers.
• Glycogen and amylopectin have one reducing end but
many nonreducing ends.
• Enzymatic processing occurs simultaneously in many
nonreducing ends.
49.
Homopolymers of Glucose:
Cellulose
• Cellulose is a linear homopolysaccharide of glucose.
– Glucose monomers form (1 4) linked chains.
– Hydrogen bonds form between adjacent monomers.
– There are additional H-bonds between chains.
– Structure is tough and water insoluble.
– It is the most abundant polysaccharide in nature.
– Cotton is nearly pure fibrous cellulose.
50.
Hydrogen Bonding in Cellulose
51.
Cellulose Metabolism
• The fibrous structure and water insolubility make cellulose a
difficult substrate to act upon.
• Most animals cannot use cellulose as a fuel source because they
lack the enzyme to hydrolyze (1 4) linkages.
• Fungi, bacteria, and protozoa secrete cellulase, which allows
them to use wood as source of glucose.
• Ruminants and termites live symbiotically with microorganisms
that produce cellulase and are able to absorb the freed glucose
into their bloodstreams.
• Cellulases hold promise in the fermentation of biomass into
biofuels.
52.
Q: What do these two have in common?
A: They both have a “sugary” shell
80% sucrose
100% N-acetylglucosamine. 10% glucose
10% fructose
53.
Chitin Is a Homopolysaccharide
• Chitin is a linear homopolysaccharide of N-acetylglucosamine.
– N-acetylglucosamine monomers form (1 4)-linked chains.
– forms extended fibers that are similar to those of cellulose
– hard, insoluble, cannot be digested by vertebrates
– structure is tough but flexible, and water insoluble
– found in cell walls in mushrooms and in exoskeletons of insects,
spiders, crabs, and other arthropods
54.
Agar and Agarose
• Agar is a branched heteropolysaccharide composed
of agarose and agaropectin.
• Agar serves as a component of cell wall in some
seaweeds.
• Agar solutions form gels that are commonly used in
the laboratory as a surface for growing bacteria.
• Agarose solutions form gels that are commonly
used in the laboratory for separation DNA by
electrophoresis.
55.
Agarose Is a Heteropolysaccharide
56.
Glycosaminoglycans
• Linear polymers of repeating disaccharide units
• One monomer is either:
– N-acetyl-glucosamine or
– N-acetyl-galactosamine
• Negatively charged
– uronic acids (C6 oxidation)
– sulfate esters
• Extended hydrated molecule
– minimizes charge repulsion
• Forms meshwork with fibrous proteins to form extracellular
matrix
– connective tissue
– lubrication of joints
60.
Heparin and Heparan Sulfate
• Heparin is linear polymer, 3–40 kDa.
• Heparan sulfate is heparin-like polysaccharide but
attached to proteins.
• Highest negative-charge density biomolecules
• Prevent blood clotting by activating protease
inhibitor antithrombin
• Binding to various cells regulates development and
formation of blood vessels.
• Can also bind to viruses and bacteria and decrease
their virulence
62.
TABLE 7-2 Structures and Roles of Some Polysaccharides
Size (number of
monosaccharide
Primer Typea Repeating unitb units) Roles/significance
Starch Energy storage: in plants
Amylose Homo- (α1S4) Glc, linear 50–5,000
Amylopectin Homo- (α1S4) Glc, with (α1S6) Up to 106
Glc branches every 24–30
residues
Glycogen Homo- (α1S4) Glc, with (α1S6) Up to 50,000 Energy storage: in bacteria and animal cells
Glc branches every 8–12
residues
Cellulose Homo- (β1S4) Glc Up to 15,000 Structural: in plants, gives rigidity and
strength to cell walls
Chitin Homo- (β1S4) GlcNAc Very large Structural: in insects, spiders, crustaceans,
gives rigidity and strength to exoskeletons
Dextran Homo- (α1S6) Glc, with (α1S3) Wide range Structural: in bacteria, extracellular adhesive
branches
Peptidoglycan Hetero-; peptides 4)Mur2Ac(β1S4) GlcNAc(β1 Very large Structural: in bacteria, gives rigidity and
attached strength to cell envelope
Agarose Hetero- 3)D-Gal (β1S4)3,6- anhydro- 1,000 Structural: in algae, cell wall material
L-Gal(α1
Hyaluronan (a Hetero-; acidic 4)GlcA (β1S3) GlcNAc(β1 Up to 100,000 Structural: in vertebrates, extracellular matrix
glycosaminoglycan) of skin and connective tissue; viscosity and
lubrication in joints
Each polymer is classified as a homopolysaccharide (homo-) or heteropolysaccharide (hetero-).
The abbreviated names for the peptidoglycan, agarose, and hyaluronan repeating units indicate that the polymer contains repeats of this disaccharide unit. For
example, in peptidoglycan, the GlcNAc of one disaccharide unit is (β1S4)-linked to the first residue of the next disaccharide unit.
63.
Glycoconjugates: Glycoprotein
• A protein with small oligosaccharides attached
– Carbohydrate ia attached via its anomeric carbon to amino acids on the
protein.
• Common connections occur at Ser, Thr, and Asn.
– About half of mammalian proteins are glycoproteins.
– Only some bacteria glycosylate a few of their proteins.
– Carbohydrates play role in protein-protein recognition.
– Viral proteins are heavily glycosylated; this helps evade the immune
system.
65.
Glycoconjugates: Glycolipids
• Lipids with covalently bound oligosaccharide
– They are parts of plant and animal cell membranes.
– In vertebrates, ganglioside carbohydrate
composition determines blood groups.
– In gram-negative bacteria, lipopolysaccharides
cover the peptidoglycan layer.
67.
Glycoconjugates: Proteoglycans
• Sulfated glucoseaminoglycans attached to a large rod-
shaped protein in cell membrane
– syndecans: protein has a single transmembrane
domain
– glypicans: protein is anchored to a lipid membrane
– interact with a variety of receptors from neighboring
cells and regulate cell growth
70.
Proteoglycans
• Different glycosaminoglycans are linked to the core
protein.
• Linkage from anomeric carbon of xylose to serine
hydroxyl
• Our tissues have many different core proteins;
aggrecan is the best studied.
72.
Proteoglycan Aggregates
• Hyaluronan and aggrecan form huge (Mr > 2 • 108)
noncovalent aggregates.
• They hold a lot of water (1000 its weight) and
provide lubrication.
• Very low friction material
• Covers joint surfaces: articular cartilage
– reduced friction
– load balancing
74.
Extracellular Matrix (ECM)
• Material outside the cell
• Strength, elasticity, and physical barrier in tissues
• Main components
– proteoglycan aggregates
– collagen fibers
– elastin (a fibrous protein)
• ECM is a barrier for tumor cells seeking to invade new
tissues.
– Some tumor cells secrete heparinase that degrades ECM.
75.
Interaction of the Cells with ECM
• Some integral membrane proteins are proteoglycans.
– syndecans
• Other integral membrane proteins are receptors for extracellular
proteoglycans.
– integrins
• These proteins link cellular cytoskeleton to the ECM and transmit
signals into the cell to regulate:
– cell growth
– cell mobility
– apoptosis
– wound healing
77.
Oligosaccharides in Recognition
78.
Glycoconjugates: Analysis
79.
Chapter 7: Summary
In this chapter, we learned about:
• structures of some important monosaccharides
• structures and properties of disaccharides
• structures and biological roles of polysaccharides
• functions of glycosylaminoglycans as structural
components of the extracellular matrix
• functions glycoconjugates in regulating a variety of
biological functions
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