Transcript Lecture 13

Carbohydrates and Glycobiology
• Carbohydrate function and classification
• Monosaccharides
– Chemical structure and properties
– Linear and cyclized forms
– Common monosaccharides and disaccharides
• Carbohydrates can be joined to phosphates, alcohols and
amines
– Hexose derivatives important in biology
• Polysacchardies: Glycogen, Starch, Cellulose, and Chitin
“The chemistry and biology of carbohydrates
has been a Cinderella field: an area that
involves much work but, alas, does not get
to show off at the ball with her cousins, the
genomes and proteins.”
Stella Hurtley, Robert Service, Phil Szuromi,
Science Vol 291, 23 March 2001
“What has rescued this Cinderella from the
shadows is no fairy godmother but a plethora
of new synthetic and analytic methods that a
previous generations of researchers would
have found nearly magical nonetheless.”
“Glycobiology has finally become part of the mainstream”
Carbohydrates
• Functions:
– As energy stores and fuels
– As metabolic intermediates
– As part of many important molecules (ATP, ribose sugar..)
– In polysaccharides (e.g. cell walls of bacterial and plant)
– Linked to proteins and lipids (glycoconjugates)
• In the extra cellular milieu, they exert effects on
cellular recognition in infection, cancer, and
immune response.
• Carbohydrates are central to many processes that are at the
core of important diseases  drug design targeting a wide
spectrum of diseases
• Classification: mono- and polysaccharides
Monosaccharides
• Two families of monosaccharides
– Aldehydes with multiple OH groups (aldose)
– Ketones with multiple OH groups (ketose)
• Chemical structures of monosaccharides
– Triose, tetrose, pentose, hexose, heptose
• Smallest one: (CH2O)3
e.g.: D(L)-glyceraldehyde
• Hexoses are the most common monosaccharides in nature
• D-ribose and 2-deoxy-D-ribose are components of
nucleotides and nucleic acids
– All except one monosaccharides have asymmetric centers
• Fisher projection representation
• Perspective representation
Cyclized forms are predominant for pentoses and hexoses
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Furanose (hemiacetal): cyclized pentose
Pyranose (hemiketal): cyclized hexose
Haworth projections
Anomers
Conformation of pyranose/furanose rings
– Pyranose ring: Chair vs. boat form
– Furanose ring: puckered
Common Monosaccharides and Disaccharides
• Common monosaccharides
– D-ribose, D-glucose, D-mannose,
D-galactose, D-fructose
• Common disaccharides and
enzymes that hydrolyze them
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Sucrose: glucose-fructose (sucrase)
Lactose: galactose-glucose (lactase)
Maltose: glucose-glucose (maltase)
Enzymes are located on epithelial
cells lining the small intestine
• Many monosaccharides are
reducing agents
• Lactose intolerance: lack of lactase
Carbohydrates Can be Joined to
Phosphates, Alcohols and Amines
• Sugars can be phosphorylated
– Key intermediates in energy generation and biosynthesis
• Carbohydrates can be joined to alcohols and amines
by glycosidic bonds
– N-glycosidic
– O-glycosidic
• Important hexose derivatives in biology
(next slide)
Some hexose derivatives important in biology
a uronic acid
a aldonic acid
Polysaccharides: Glycogen
• Polysaccharides
– Homosaccharides
(branched and unbranched)
– Heterosaccharides
(branched and unbranched)
• Glycogen
– Store of glucose in animal
cells
• 14 linkage with 16
branch
– Exist in granules inside the
cell tightly bound with
enzymes for glycogen
synthesis and degradation
Polysaccharides: Starch
• Starch
– Store of sugar in plants
– Two forms
• Amylose: unbranched
– Glucose, -1,4 linkage
• Amylopectin: branched
– Glucose, 1 -1,6 per 30 -1,4
– -amylase: hydrolyze -1,4 linkages
Curved Polysaccharide Chain in amylose-Unbranched Starch
Polysaccharides: Cellulose and Chitin
• Cellulose
– Plant polysaccharide
– Serve as a structural not nutritional role
– Unbranched polymer of glucose, -1,4 linkages
– Linear chains; forming fibers; high tensile strength
– Mammals lack cellulases and so cannot digest wood and vegetable
fibers
• Chitin
– Exoskeletons of insects
– Unbranched polymer of NAG, -1,4 linkages
– Long straight chains; structural roles
Linear Structure of Cellulose (D-glucose  1 4 Linkage)
Extended
chain
Give extended chain
Intra-chain
H-bonds
Inter-chain
H-bonds
Bacterial Cell Walls Contain Peptidoglycans
NAG: N-acetylglucosamine
NAM: N-acetylmuramic acid
 1 4 linkage
A number of layers;
Provide strength to the cell;
Keep shape of the cell;
Antibacterial agent act on
cell wall –peptidoglycan;
Pennicillin; Lysozyme
Structure of the cell wall of
staphylococcus aureus
Glycosaminoglycans are components of the extracellular matrix
Heteropolysaccharide;
linear
a gel-like material
the extracellular space
in the tissues of
multicellular animals
Repreating disaccharides;
C-6 carbon in glucose/galactose/
mannose is oxidized to carboxyl
N-acetylglucosamine (NAG) or
N-acetylgalactosamine;
Uronic acid (in most cases):
D-glucuronic acid, or
L-iduronic acid
One or more –OH is esterified with sulfate
High density of negative charges on glycosaminoglycans
(-COO-, -OSO3-)
extended
conformation
Uronic acid
(most cases)
NAG or N-acetylgalactosamine
Hyaluronate
Very long!
In some glycosaminoglycans,
The amino sugar is
Chondroitin
4-sulfate
short
Keratin
sulfate
short
esterified with sulfate
High density of negative charges
extended conformation in solution
Glycosaminoglycans are attached
To extracellular proteins to
form proteoglycans