Chapter 11
Carbohydrates
Carbohydrates are aldehydes or ketone with multiple
hydroxyl groups
<Role of Carbohydrate>
• Energy stores, fuels, and metabolic
intermediates
• Structural framework of DNA and RNA
• Structural elements in the cell walls of
bacteria and plans
• Linked to many proteins and lipids (cell-cell
communication)
Carbohydrates as mediators of cellular
interactions
• Structural diversity in size and
stereochemical configuration
• Built from monosaccharides
• Attach to lipids and proteins
Glycomics: Studies on oligosaccharide
structures and functions
11.1 Monosaccharides are aldehydes or ketones with
multiple hydroxyl group
Aldehyde group
Ketone group
-Monosaccharides : the simplest carbohydrate. Important
fuel, building blocks for nuclearic acid
-The smallest monosaccharides:
Stereoisomer
- Enantiomer = mirror images of each other
※ Fischer projection
-Horizontal bond : in frond of the page
-Vertical bond : behind of the page
-Clear and simple views of the
stereochemistry at each carbon center.
D- aldose
Three carbon
triose
Four carbon
tetrose
Five carbon
pentose
Six carbon
hexose
D- ketose
Three carbon
triose
Four carbon
tetrose
Five carbon
pentose
Six carbon
hexose
Pentoses and hexoses cyclize to form furanose and
pyranose rings
-The predominant forms of ribose, glucose, fructose, and
many other sugars are cyclized into rings.
-Ring forms are energetically stable.
-Aldohexose glucose : C-1 aldehyde reacts with the C-5.
-Ketohexose fructose : C-2 keto group reacts with a
hydroxyl group of C-5 or C-6.
pyranose
- α-D-glucopyranose: Hydroxyl
group is on the opposite side of
the ring from the CH2OH.
C-1
- β-D-glucopyranose: Hydroxyl
group is on the same side of the
ring from the CH2OH.
- C-1 carbon atom : anomeric carbon atom
- α and β form : anomer
- In case of glucose : 1/3 α anomer, 2/3 β anomer
furanose
※ Haworth projection : The
approximate plane of the ring is
perpendicular to the plane of the paper.
-Heavy line : projecting toward the
reader.
-Easy depiction of the stereochemistry
of sugars.
- Fructose forms both pyranose and furanose ring.
Pyranose and furanose rings can assume different
conformations
-The six-membered pyranose ring is not planar.
-Pyranose rings adopt two classes of conformations
-Chair : substituents on the ring carbon atoms have two
orientation ; axial and equatorial.
-Boat : glucose boat form disfavored because it is quite
sterically hindered.
a : axial
e : equatorial
-The chair form is more stable owing to less steric
hindrance because the axial positions are occupied by
hydrogen atoms.
-The five-membered furanose ring is also not planar.
-Envelope form : four atoms are nearly coplanar and the
fifth is about 0.5Å away from this plane.
Monosaccharides are joined to alcohols and amines
through glycosidic bonds
-Monosaccharides react with alcohols and amines to
form modified monosaccharide.
-Ex> D-glucose react with methanol.
-O-glucosidic bond : OCH3
-N-glucosidic bond : NR2
Ex) Nucleotide; ribose+adenine
- Methyl glycopyranoside differ in reactivity from the
parent monosaccharides.
Fehling’s solution
-Unmodified glucose reacts with oxidizing agents such as Cu2+ because
the open-chain form has a free aldehyde group that is readily
oxidized.(=reducing sugar)
-Methyl glucopyranoside do not react .(=non-reducing sugar)
-Glucose react with hemoglobin to form glycosylated hemoglobin. diabete
- Carbohydrates can be modified by the addition of
substituents. Such modified carbohydrates are often
expressed on cell surfaces.
Phosphorylated sugars are key intermediates in energy
generation and biosyntheses
- Phosphorylation is a common modification of sugars.
Ex> The first step in the breakdown of glucose to obtain energy is its
conversion into glucose 6-phosphate.
-Phosphorylation makes sugars anionic(negative charge) to prevent sugars from
leave the cell spontaneously by crossing membrane
-Reactive intermediates in purine and pyrimidine biosyntesis
11.2 Complex carbohydrates are formed by the
linkage of monosaccharides
-Glycosidic bond : the linkage of two or more monosaccharides
by O-glycosidic bond.
-Various glycosidic linkage is possible.
-Structurally diverse molecules.
Sucrose, lactose, and maltose are the common
disaccharides
-A transport form of carbohydrates in plants.
-Obtained commercially from cane or beet.
-Glucose + fructose
-Can be cleaved by sucrase.
-Disaccharide of milk.
-Galactose + glucose. By β-1,4-glycosidic linkage
-Can be cleaved by lactase in human being.
-Can be cleaved by β-galactosidase in bacteria.
-Glucose + glucose. By α-1,4-glycosidic bond.
-Can be cleaved by maltase.
-Sucrase, lactase, maltase are located on the outer
surfaces of epithelial cells lining the small intestine.
Microvillus
Glycogen and starch are mobilizable stores of glucose
-Polysaccharides : the linkage of multiple monosaccharides.
-Role : energy storage and maintaining the structural
integrity.
-Homopolymer : all of the monosaccharides are the same.
-Glycogen : storage form of glucose.
large, branched polymer.
-Branch point : α-1,6-glycosidic bond.
present about once
in 10 unit.
-Starch : nutritional reservoir of carbohydrates in plants.
-Two types of starch = amylose and amylopectin.
-Amylose : unbranched, α-1,4-linkage.
-Amylopectin : branched, one α-1,6-linkage per 30 α-1,4linkages.
Cellulose, the major structural polymer of plants, consists
of linear chains of glucose units
-Cellulose : major polysaccharide of glucose found in plants.
structural role rather than nutritional role.
most abundant organic compound in the biosphere.
β-1,4-linkage of glucose = long, straight chains. Optimal for
fiber having a high tense strength
α-1,4-linkage (starch and glycogen) = helix conformation. Suitable
for accessible store of sugar.
- Proteoglycan : proteins attached to a particular type of
polysaccharide called glycosaminoglycan (95% by weight). As joint
lubricants and structural components in connective tissue
-Many glycosaminoglycans are anionic polysaccharide chains made of
repeating disaccharide units containing glucosamine or galactose.
-Sugars have a negatively charged carboxylate or sulfate.
Cartilage key components: aggrecan, collagen
- collagen: triple helix provides structure and tensile strength.
※ Aggrecan : shock aborber.
- Large protein of 2397 amino acids.
- Three globular domain.
-The first domain binds to
glycosaminoglycanname (=hyaluron).
Specific enzymes are responsible for oligosaccharide
assembly
- Glycosyltransferase : catalyze the formation of the
glycosidic bonds that link monosaccharide.
intermediates
ABO blood
type
-Carbohydrates are attached to proteins and lipids on the surfaces of the red
blood cells.
-The A and B antigens are formed by the addition of one extra
monosaccharide by type A transferase and type B transferase respectively.
-Why are different blood types present in the human population? Arms race!
11.3 Carbohydrates can be attached to proteins to
form glycoproteins
-A carbohydrate group can be covalently attached to a
protein to form a glycoprotein.
-Many glycoproteins are components of cell membranes.
-Sugars are attached either to the amide nitrogen atom or
to the oxygen atom
N-linkage
O-linkage
Attach atom
Amide nitrogen atom
Oxygen atom
Residue
Asparagine
Serine or threonine
sequence
Asn-X-Ser / Asn-X-Thr
no
Carbohydrates can be linked to proteins through
asparagine (N-linked) or through serine or threonine(Olinked) residues
- All N-linked oligosaccharides have in common a
pentasaccharides core consisting of three mannose and
two N-acetylglucosamine residue.
※ Erythropoietin (EPO)
- Glycoprotein hormone.
- Secreted by the kidneys and
stimulates the production of
red blood cells.
- 165 amino acids.
- Three N-glycosylation and one O-glycosylation.
(40% carbohydrate by weight)
- Glycosylation of EPO enhances the stability of the
protein in blood.
- Unglycosylated EPO has only about 10% of the
bioactivity of the glycosylated. Removed by kidney
- recombinant human EPO for anemias, Drug-testing
Protein glycosylation takes place in the lumen of the
Endoplasmic Reticulum and in the Golgi complex
- Protein glycosylation takes
place inside the lumen of the
ER and in the Golgi complex.
-N-linked glycosylation begins
in the ER and continues in the
Golgi.
-O-linked glycosylation takes
place in the Golgi.
※ Dolichol phosphate : lipid molecule located in ER
membrane and containing about 20 isoprene units.
20X
※ Phosphate group : the site of attachment of the large activated
oligosaccharide. And is transferred to Asn residue of the growing
polypeptide chain.
Activated sugar and complex enzyme are located on the ER lumen;
- O-inked sugar units are
fashioned.
- N-linked sugar are
modified in many
different ways.
Golgi is Major Sorting
Center
Errors in glycosylation can result in pathological conditions
-Glycosylation is important for the processing,
stability, and targeting of proteins.
Ex> I-cell disease. (=mucolipidosis)
-Lysosomal storage disease.
-A carbohydrate marker directs degradative enzymes from
Golgi to lysosome.
-Patients having I-cell disease cannot attach sugar(mannose) to
degradative enzymes. Enzymes cannot be targeted to lysosome
but secreted to blood.
-Inclusion body of undigested glycosaminoglycans and glyco
lipids in lysosome.
-Psychomotor retardation and skeletal deformities.
Lysosome target marker
Oligosaccharides can be “sequenced”
Detachment of oligosaccharide from the protein by N-glycosidase F
MALDI-TOF or other mass spectrometric techniques
Cleavage of the oligosaccharide with enzymes of varying specificities
MALDI-TOF or other mass spectrometric techniques
Glycosylation site?
Repeat and collect information
11.4 Lectins are specific carbohydrate-binding
proteins
• An enormous number of patterns in the composition and
structure of surface sugars are possible because…
1). Different monosaccharides can be joined
2). C-1 linkage can have either α and β configuration
3). Branching
Carbohydrate = information rich molecule.
Lectins promote interactions between cells
-The diverse carbohydrate structures displayed on cell
surface → cell-cell and cell-environment interaction.
※ Lectin(from the Latin “to select”)
-Bind to specific carbohydrate.
-Function : cell-cell contact.
-Contain two or more binding sites for carbohydrate.
-C type lectin : Ca2+ requiring, found in animal.
※ Selectin : member of C type family. Bind to sites of
injury in the inflammatory response.
L selectin: Lymph-node vessel
E selectin: endothelium
P selectin: activated blood platelet
Embryo implantation: L selection of embryo
-Plants also are rich in lectins. Potent insecticides
-The binding specificities of lectins from plants have been
well characterized.
-E.coli bacteria adhere to the gastrointestinal tract by lectins on the
E.coli surface
Influenza virus binds to sialic acid residues
-Some viruses gain entry into host cells by adhering to
cell-surface carbohydrates.
Ex> influenza virus recognizes sialic acid residues through
“hamagglutinin” protein. (H)
After the virus penetrates
the host cell, another viral
protein,
“neuraminidase”(N),
cleaves the glycosidic bond
to free the virus.
Tamiflu and Relenza are
the inhibitor of
neuraminidase
Ex> H5N1(Avian Influenza),
H1N1(Swine Influenza)