David L. Nelson and Michael M.

Cox

Lehninger Principles of
Biochemistry
Fourth Edition

Chapter 7:
Carbohydrates and Glycobiology

Copyright © 2004 by W. H. Freeman & Company

• polyhydroxy aldehydes or ketones,
ketones or substances that
yields such compounds on hydrolysis
• Most abundant biomolecules
• By photosynthesis, 100 billion CO2 & H2O

cellulose and plant products
• (not all) empirical formula
(CH2O)n
• Their Functions in livings
– A dietary staple
– Energy-yield pathway in non-plants
– Structural & protective element in cell wall of bacteria,
plants and in connective tissue of animals
– Lubricant in skeletal joints
– Recognation & adhesion between cells
– Signals (L+C or L+P: glycoconjugates)
• Types (size)
– Monosaccharides (monomer)
• Simple sugar
• A single polyhydroxy aldehyde or ketone unit
• Most abundant
six-carbon sugar D-glucose
(dextrose)
– Oligosaccharides (2-20 monomer)
• Disaccharides: 2 monomers
– Sucrose (abundant):D-Glucose+D-Fructose
• Not free, linked to other biomolecules in cell
– Polysaccharides (>20 monomer)
• Starch: chain
Glycosidic linkage
• Glycogen:branched
Monosaccharides and Disaccharides
• Either aldehydes or ketones with two or
more hydroxyl groups
• Colorless, soluble in water, crystalline
• Most sweet
• A carbonyl (aldehyde or ketone) group +
many hydroxyl group
– Aldose: if carbonyl at the tip
– Ketose: if carbonyl at any other
Monosaccharides and Disaccharides

• Simplest: 2-carbon trioses:

• Glyceraldehyde (an aldotriose)
• Dihydroxyacetone (a ketotriose)
• How to name MS acc. # of Carbon
• 3C
triose
• 4C
tetrose
• 5C
pentose
• 6C
hexose
• 7C
heptose
 CH
asymetric centers
• # of Chiral center: >1
• Glyceraldehyde
1 chiral center
• # of stereoisomer= 2n (n=# of chiral center)
• X-ray crystalography for 3D but
• Fisher projection formulas to represent them 3D
on paper
• Stereoisomers of sugar can be L or D
– 6 C means 4 chiral C. So 24=16 stereoisomers
– 8
D; 8
L
 How to define which one is D or L
Find the carbonyl Carbon •Find the farest carbon

Compare with gyceraldehyde; if hydroxyl

on left
D; if not
L
Epimers: sugars
configuratonal
difference only
one C atom
4-5 carbon ketoses
“ul” into the corresponding aldose
 In aqueous solution:Cyclic
• >4 carbon backbonded MS
cyclic (ring)
• Carbonyl (aldehyde or ketone)--- O of
hydroxyl of (mostly last) any C
• Aldehyde + alchol = hemiacetal
• Ketone + alcohol = hemiketals
 Two stereoisomers while cyclic

α and β stereoisomers
Six-membered ring
pyranose

Mutaration
interconvertion of alfa to

beta
Five-membered
furanose
In normal aquoes soltion
1/3
α-D glucopyranose
2/3
β -D glucopyranose
Very small
linear and glucofuranose
2 possible
conformation
(without bond
breaking)
2 chair forms of
pyranose rings
Hexose Derivatives

Bacterial cell wall

Bacterial cell wall

In animals as glycoconjugate
Reducing sugars: sugars that reduce Fe3+
(ferric) or Cu2+ (cupric)
Reducing agent:Monosaccharides
carboxyl
carbonyl
BUT TODAY WE USE A DIFFERENT METHOD
Disaccharides’ Glycosidic Bond
• DS =MS + O-glycosidic bond + MS
Between anomeric carbon of
one and hydroxyl of another

glycosidic bond:easly hydrolyzed by acid

but base

Boil wth dilute acid
monosaccharides

Non-reducing Reducing end
end Why
Why because it is
because it is free.
not free.
 How to name DS
3.
1. Glycosidic bond’s
Look at first onedirection is α or β.
whetherinitparanthesis 4. Name
2. Name-Nonreducing
second residueend
In example,
Example:
it4)is
(1
β sugar;
If 3.residuefurano
write the or
bondpyrona
İn milk

D enintomer and pyronose is common
abbreviated nomenculator

In plant not by animals

is nonreducing sugar

It means no free anomeric carbon

Double headed arrow
Circulating fluid (hemolymph) of insects, energy fuil
 Polysaccharides (glycans)
• Classification
– identity of their recurring MS
– Size
– Branch
– Types of bonds
 Polysaccharides (glycans)
• Homopolysaccharides
– Single type of monomer
• Storage (glycogen, starch)
• Structural (chitin, cellulose)
• Heteropolysaccharides
– 2 or > types
– Extrocellular support
Homopolysaccharides as energy source

• Starch (plants) and Glycogen

(animals)
• Both
intracellular granules
• Heavily hydrated (many –OH)
• Readly dissolved
 Starch
• Two types
• Amylose
• Amylopectin
• Amylose:
• Long, unbranched
• (α 1-4) linkages of D-glucose
• Amylopectin
– Up to 100 million Dalton
– Branched
• (α 1-6) at branches
• One branch/(24-30 residues)
 One reducing end

Many nonreducing end

 Glycogen
• Storage in animals (mostly liver; some skel)
• Like amylopectin but more branched (1/8-12
residue)
• More compact than starch
• Several million
• Degraded enzyme work from nonreducing end
• Q:Why glycogen? Why not all glucoses one by
one?
– A: [glycogen]:0.01 µM but if it were degraded
[glucose]: 400.000 µM
osmolarity
 Dextran
• Bacterial and yeast PS
• (α1
6) linked poly-D-glucose
• Branched with (α1
3) in all, ((α1
2)&
(α1
6) in some)
• Some sticky dextran by bacteria (streptococcus
mutant) makes dental plaque
• Synthetic dextran in
• artifical blood
• Sephadex
• etc
 Homopolysaccharides as structural
roles
1. Cellulose

2. Chitin
 1. Cellulose
• Fibrous, tough, water-insoluble
• in cell walls of plants (stems, trunks etc.)
– Cotton ~100% cellulose
• Linear, unbranched (10000-15000 D-glucose units)
• Like amylose, amylopectin, glycogen
– Main difference
β (β
β 1


4)
• α-amylase: enzyme breaking (α 1
4) amylose,
starch, glycogen but not cellulose
• Cellulase: enzyme breaking (β 1
4) of cellulose
– Trichonympha
Termites
– Wood-rot fungi and bacteria
 2. Chitin
• Linear with N-acetylglucosamine in β-
linkage
• Exoskeloton of nearly a million species of
arthropodsinsects, lobsters, crabs etc
• Most abondunt PS after cellulose in nature
Only difference betwen chitin and cellulose: Acetylated amine

Cellulose
 3D of PS
• Depends on interactions
• Hydrogen bonding
• Hydrophobic
• Van der-Walls
• Electrostatic interaction (polymer with charged res.)
 Bacterial&Algal Cell Walls

Heteropolysaccharides

• Cell wall against lysis

• Lysozyme
degrade cell wall (β1-4)gylcosidic
bond btwen them
• Tears
• Baacteral viruses
 Extracellular matrix:
Glycosaminoglycans
• Heteropolsaccharides
• Gel-like
• Extracellular matrix: glycosaminoglycans +
proteins
• Glycosaminoglycans: polymers of repeting
disaccharides (monomer)
>1 million D

Vitrous Component of
humor extracellular
(liquid matrix of tendons
inside the and cartilage
eye ball)
 Other glycosaminglycans

• Shorter than hyaluronate

• Proteoglycans (linked to proteins)

Tensile strength of cartilage, tendons, ligaments, walls of aorta.
In cornea, cartilage, bone and a variety of horny structure (horn,
hair etc)
 Glycoconjugates: Proteoglycans,
Glycoproteins, Glycolipids

• Cell-cell recognation
• Cell-cell adhesion
• Cell migration during development
• Blood cloting
• İmmune response
• Wound healing
• Glycoconjugates: charbohydrates + (lipid or protein)
– Proteoglycans: CH + membrane or secreted protein
• Glycosaiminoglycans moiety
main part
• Major parts of connective tissue
– Glycoproteins: a few oligosacch.
• Outher surface of plasma membrane
• In extracellular matrix
• Blood
• İn cell (golgi, lysosomes, secretory granules)
• Their cahins
specific, informative
– Glycolipids
• Membrane lipids attached oligosac.
 Proteoglycans
• Glycosaminoglycan-coating
macromolecules (30 members of the family)
– Cell surface (integral protein)
– Extracellular matrix
• Basal lamina: heparin sulfate chain + trisaccharide
bridge + core protein (20kD-40 kD)
1

3
Proteoglycan aggregates
(~2000kD) =aggrecan core
protein(250kD) +CS +KS

Function:make the extracellular

matrix strength (with collagen
etc)
Multiple binding sites for matrix elements and
ligands (signal)

Multiple binding sites

 Glycoproteins
• Protein + carbohydrate (its moiety small)
Glycolipids and Lipopolysaccharides
• Membrabe components
• Glycolipids: Ganglioisedes (membrane lipid +
CH)
– Blood groups
• Lipopolysaccharides
– Found on the surface of some bacteria
– Target for antibiotics
– Toxic
• Lower blood pressure
 CH as informative molecule
• CH more nformative than others
• 14 units :
– CH 1.44x1015
– NA: 4096
– Peptide: 6.4x107
• Lectin: proteins that bind CH with high affinity
and specificity
– Function:
• Cell-cell recognation
• Signaling
• Adhesion process
• İntacelullar targeting of newly synthesized proteins
• Some hormones and RBC are marked with
Oligos. Moiteies
– Funciton: affect their half-life: if you remove,
half-life decrease

Selectins: a family of plasma membrane

lectins
• F: cell adhesion
• Cell-cell recognation
Cholera toxin (vibrio cholera)
oligosaccharide of GM1, ganglioside, of
intestinal epithelial cells
diarrhea
Lectins
~intracellular and highley
specific for oligos.
FIGURE 7–35 Details of lectin-
carbohydrate interaction. (a)
X-ray crystallographic studies
of a sialic acid–specific lectin
(derived from PDB ID 1QFO)
show how a protein can
recognize and bind to a sialic
acid (Neu5Ac) residue.
Sialoadhesin (also called siglec-
1), a membranebound lectin of
the surface of mouse
macrophages, has a sandwich
domain (gray) that contains the
Neu5Ac binding site (dark
blue). Neu5Ac is shown as a
stick structure.
(b) Each ring substituent
unique to Neu5Ac is
involved in the interaction
between sugar and lectin:
the acetyl group at C-5 has
both hydrogen-bond and
van der Waals interactions
with the protein; the
carboxyl group makes a salt
bridge with Arg97; and the
hydroxyls of the glycerol
moiety hydrogen-bond with
the protein
(c) Structure of the bovine
mannose 6-phosphate receptor
complexed with mannose 6-
phosphate (PDB ID 1M6P). The
protein is represented here as a
surface contour image, with
color to indicate the surface
electrostatic potential: red,
predominantly negative charge;
blue, predominantly positive
charge. Mannose 6-phosphate is
shown as a stick structure; a
manganese ion is shown in
green.
Mannose 6-phosphate is
hydrogen-bonded to Arg111 and
coordinated with the manganese
ion (green). The His105
hydrogen-bonded to a
phosphate oxygen of mannose 6-
phosphate may be the residue
that, when protonated at low pH,
causes the receptor to release
mannose 6-phosphate into the
lysosome.
Polar sidec of galactose with polar ones of protein and
hydrophobic sides with indolyl moiety of Trp.
FIGURE 7–37 Roles of
oligosacharides in recognition and
adhesion at the cell surface.(a)
Oligosaccharides with unique structures
(represented as strings of hexagons),
components of a variety of
glycoproteins or glycolipids on the outer
surface of plasma membranes, interact
with high specificity and affinity with
lectins in the extracellular milieu. (b)
Viruses that infect animal cells, such as
the influenza virus, bind to cell surface
glycoproteins as the first step in
infection. (c) Bacterial toxins, such as
the cholera and pertussis toxins, bind to
a surface glycolipid before entering a
cell. (d) Some bacteria, such as H.
pylori, adhere to and then colonize or
infect animal cells.
(e) Selectins (lectins) in the plasma
membrane of certain cells mediate cell-
cell interactions, such as those of T
lymphocytes with the endothelial cells
of the capillary wall at an infection site.
(f) The mannose 6-phosphate
receptor/lectin of the trans Golgi
complex binds to the oligosaccharide of
lysosomal enzymes, targeting them for
transfer into the lysosome.