Download Document

Biochemistry
An Introduction to the Chemistry of Life
for Students of veterinary medicine
Dr Nader Vojdanifar
What is Life Made of?
 Physical and Chemical sciences alone
may not completely explain the nature of
life, but they at least provide the essential
framework for such an explanation.
 All students of VM must have a
fundamental understanding of organic
chemistry and biochemistry.
Organic Chemistry
 Organic chemistry is the study of Carbon
compounds.
 Organic compounds are compounds
composed primarily of a Carbon
skeleton.
 All living things are composed of organic
compounds.
Organic Chemistry
 What makes Carbon Special? Why is
Carbon so different from all the other
elements on the periodic table?
 The answer derives from the ability of
Carbon atoms to bond together to form
long chains and rings.
Organic Chemistry
Organic Chemistry
Carbon can covalently bond with up
to four other atoms.
Carbon can form immensely
diverse compounds, from simple
to complex.
Methane with 1 Carbon
atom
DNA with tens of Billions of
Carbon atoms
Biochemistry
 Biochemistry is a special branch of
organic chemistry that deals with matter
inside the living cell called Protoplasm.
 Protoplasm is an enormously complex
mixture of organic compounds where
high levels of chemical activity occur.
Biochemistry
 How much
biochemistry do you
need to know for this
course?
 1. You need to know
the structure of
organic molecules
important to major
biological processes.
2. You will be
expected to learn
the basic
biochemical
processes of
major cell
functions, such as
photosynthesis,
respiration, and
protein synthesis.
Primary Organic
Compounds
You are expected to
learn the structure
and functions of
these organic
compounds:
1.
2.
3.
4.
Carbohydrates
Lipids
Proteins
Nucleic Acids
Polymers ands Monomers
 Each of these types of molecules are
polymers that are assembled from single
units called monomers.
 Each type of macromolecule is an
assemblage of a different type of
monomer.
Monomers
Macromolecule
Carbohydrates
Monomer
Monosaccharide
Lipids
Proteins
Not always polymers;
Hydrocarbon chains
Amino acids
Nucleic acids
Nucleotides
How do monomers form
polymers?
 In condensation reactions (also called
dehydration synthesis), a molecule of
water is removed from two monomers as
they are connected together.
Hydrolysis
 In a reaction opposite to condensation, a
water molecule can be added (along with
the use of an enzyme) to split a polymer
in two.
Carbohydrates
 Carbohydrates are made of carbon,
hydrogen, and oxygen atoms, always in a
ratio of 1:2:1.
 Carbohydrates are the key source of
energy used by living things.
 The building blocks of carbohydrates are
sugars, such as glucose and fructose.
Carbohydrates

We may think of carbohydrates as
sugar and spice and everything nice
Carbohydrates
 What do the roots
mono-, di-, oligo-,
and poly mean?
 Each of these roots
can be added to the
word saccharide to
describe the type of
carbohydrate you
have.

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
Monosaccharides
Aldoses (e.g., glucose)
Ketoses (e.g., fructose)
have an aldehyde group at have a keto group, usually
one end.
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
How do two monosaccharides
combine to make a
polysaccharide?

Polysaccharides
homopolysaccharide
heteropolysaccharide
Numbers, Groups and Names
“OSE” is the suffix denoting a sugar and “ULOSE” denotes a keto sugar. The
monosaccharides you will encounter in biochemistry have 3, 4, 5, 6, and 7 carbons. Prefixes
such as tri, tetra, penta, hexa, and hepta alert you to the number. Know these prefixes (click
1). You will also see “aldo” and “keto” to denote the type of functional group (click 1). The
term aldopentose denotes two structural features, chain length and functional group. Aldo
refers to aldehyde and keto to ketone. The figures show an aldopentose and a ketohexose.
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
Tri-
C
C
C
C
Tetra-
C
C
C
C
C
Penta-
Hexa-
C
O
C
H
C=O
C
C
C
C
C
Aldopentose
C
C
C
C
Ketohexose
Hepta-
An aldo sugar always has the “carbonyl” group on C-1, a keto sugar has it on C-2. This is good
to remember. –OH groups are not indicated by this terminology. More terms are need,
therefore, to describe a specific sugar. Click to go on.
Balls and Sticks:
All sugars have one carbonyl group and at least two –OH groups. All
have at least one –CH2OH group. What distinguishes one from another is the
right-left orientations of internal –OH groups. Stereochemistry is best learned by
using balls and sticks. For example, D-glucose, an aldohexose, is show as (click
1). The ball represents the –CHO group, the sticks –OH groups. Because a –
CH2OH group is common to all sugars, it is not necessary to draw this group each
time.
D-glucose
L-glucose
D-fructose
D-mannose
L-mannose
D-ribose
The red line shows the –OH group whose left/right orientation determines if its a D- or
L-sugar. L-glucose is the mirror image of D-glucose (click 1). Focus on chiral center
orientations to learn the sugars. Keto sugars can only be represented by sticks, with
a = to show the keto group (click 1). Ball and stick representations are a quick way
to help you see differences between sugars and imprint these in you memory (click 1)
Rules for Configurations
What you saw on the previous slide was the importance of –OH group
orientation to pinpoint a specific sugar’s name. Now you will see that internal
configurations have their own prefixes, such as “gluco, manno, galacto, fructo,
etc. Configuration prefixes help you compare sugars. Here are examples of D
sugar configurations (click 1).
Note that glucose and galactose differ
by orientation around C-4 (click 1) and
glucose and mannose differ at C-2
(click 1). The other aldohexoses are
allose with all –OH groups on the same
side (click 1) to idose (the idiot sugar)
that can decide which side to put its –
OH groups (click 1).
gluco
ribo
galacto
arabino
manno
xylo
lyxo
gulo
allo
erythro
ido
threo
altro
talo
fructo
In the pentoses, one sees that
ribose has all –OH groups on the
same side (click 1). The tetroses
differ by orientation around C-2.
Fructose is set apart because of
the keto group on C-2 (click 1).
But, note that C-3 to C-6 of
fructose have the same
configuration as glucose (click 1).
Click to go on.
D vs L Designation
CHO
CHO
D & L designations
are based on the
configuration about
the single
asymmetric C in
glyceraldehyde.
H
OH
HO
D-glyceraldehyde
OH
CH2OH
D-glyceraldehyde
H
L-glyceraldehyde
CHO
C
C
CH2OH
CH2OH
H
The lower
representations are
Fischer Projections.
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).
D vs L Classification Simplifies Names
Recall, aldohexoses have 4 chiral centers, or 16 (24) stereoisomers possible. Does
that mean 16 individual sugar names? No. When we denote aldohexoses as D or L, only 8 (23)
D-steroisomers are possible. This is because the D, L designation fixes one of the centers.
Therefore, of the 16, 8 D and 8 L will have the same name. Common aldohexoses you will
encounter in your studies are D-glucose, D-mannose, and D-galactose. Know these and Dfructose (click 1).
D-glucose
L-glucose
D-mannose
D-galactose
D-fructose
D-ribose
D-xylose
D-erythrose
D-threose
Applying the same rule, there are 4, D-aldopentoses and 2, D-aldotetroses. The common Daldopentoses are D-ribose and D-xylose (pronounced zy-lose) (click 1). If you use your
imagination you should see an X in the structure of xylose (click 1). Perhaps calling xylose
the “idiot sugar of pentoses” will help you remember the structure. The aldotetroses are
represented by D-erythrose and D threose (click 1). D-erythrose, like D-ribose has all –OH
groups on the right. D-threose has one right and one left (another idiot sugar?). Click to go
on.
Terminology
We end the lesson by considering the terminology that describes the
properties of sugars. Understand that terminology is needed to draw comparisons
between structures. So, the question you must ask is “how does this term tell me how
two sugars differ? Remember isomers must have something in common as well as
different.
1. Glucose and galactose are epimers (click 1).
The word epimer is used when comparing sugars with multiple chiral centers. It literally
says only one center is different.
2. L-glucose is the enantiomer of D-glucose (click 1)
This means that one is the mirror image of the other.
3. Alpha D-glucose is the anomer of beta D-glucose (click 1)
Anomers differ in the stereochemistry around the ring-forming carbon. Since alpha and beta
differ in only one chiral center, anomers can also be considered epimers
4. Glucose and galactose are diastereoisomers (click 1)
Diastereoisomers have different physical properties. Generally optical isomers with one chiral
center differ only in the direction they rotate plane-polarized light. Diastereoisomers differ both in
rotation and physical properties. D-galactose and D-glucose, for example have the same
chemical formulas (C6H12O6), the same straight carbon chain and the same number of –OH
groups. But, besides rotation, they also differ in melting point, solubility, heat of vaporization, etc.
That is why they are considered “dia” (lit., opposed to being simple) “stereoisomers”.
D-Stereochemistry of Glucose
Convention for
the Fischer
projection:
CHO
H C OH
HO C H
Carbonyl (#1C) is
at the top.
OH to right = "D"
OH to left = "L"
H C OH
H C OH
Penultimate C
CH2 -OH
Glucose is assigned the D stereochemistry
because the penultimate carbon atom is D.
Hemiacetal & hemiketal
formation
H
An aldehyde
can react with
an alcohol to
form a
hemiacetal.
C
H
O
+
R'
OH
R'
O
R
aldehyde
C
OH
R
alcohol
hemiacetal
R
A ketone can
react with an
alcohol to form
a hemiketal.
C
R
O
+
"R
OH
R'
ketone
"R
O
C
R'
alcohol
hemiketal
OH
Pentoses and
hexoses can cyclize
as the ketone or
aldehyde reacts
with a distal OH.
Glucose forms an
intra-molecular
hemiacetal, as the
C1 aldehyde & C5
OH react, to form
a 6-member
pyranose ring,
named after pyran.
1
H
HO
H
H
2
3
4
5
6
CHO
C
OH
C
H
D-glucose
C
OH
(linear form)
C
OH
CH2OH
6 CH2OH
6 CH2OH
5
H
4
OH
H
OH
3
H
O
H
H
1
2
OH
-D-glucose
OH
5
H
4
OH
H
OH
3
H
O
OH
H
1
2
OH
-D-glucose
These representations of the cyclic sugars are
called Haworth projections.
H
Rings
Only 5-, 6-, and 7-carbon sugars form rings. The ring can either have 6 atoms
(pyranose) or 5 atoms (furanose). The –OH group on a hexose will attack C-1 to form a ring
(click 1). When the ring forms, a new asymmetric carbon is introduced into the molecule
(click 1). The –OH on the new asymmetric carbon can be drawn so as to appear on the
same side of the ring-forming oxygen (alpha sugar) (click one), or it can be drawn to be on
the side away from the ring-forming oxygen (beta sugar) (click 1).
O
C
H
C-OH
HO-C
H
OH
HO
*C
C-OH
H
C
C-OH
HO-C
HO-C
C-OH
C-OH
C-OH
C-OH
C
CH2OH
CH2OH
CH2OH
alpha D-glucopyranose
beta D-glucopyranose
O
C
O
You should now be able to see how all the nomenclature discussed thus far is needed to
pin down a specific monosaccharide. To help you see this, consider the alternatives to
alpha D-glucose. Its alpha (not beta), D (not L), gluco (not galacto, manno, fructo, etc.)
pyranose (not furanose). The nomenclature is precise for just one sugar. Click one to
go on.
CH2OH
1
HO
H
H
2C
O
C
H
C
OH
C
OH
3
4
5
6
HOH2C 6
CH2OH
D-fructose (linear)
H
5
H
1 CH2OH
O
4
OH
HO
2
3
OH
H
-D-fructofuranose
Fructose forms either
 a 6-member pyranose ring, by reaction of the C2
keto group with the OH on C6, or
 a 5-member furanose ring, by reaction of the C2
keto group with the OH on C5.
6 CH2OH
6 CH2OH
5
H
4
OH
H
OH
3
H
O
H
H
1
2
OH
-D-glucose
OH
5
H
4
OH
H
OH
3
H
O
OH
H
1
2
H
OH
-D-glucose
Cyclization of glucose produces a new asymmetric
center at C1. The 2 stereoisomers are called
anomers,  & .
Haworth projections represent the cyclic sugars as
having essentially planar rings, with the OH at the
anomeric C1:
  (OH below the ring)
  (OH above the ring).
H OH
H OH
4 6
H O
HO
HO
H O
HO
H
HO
5
3
H
H
2
H
OH 1
OH
-D-glucopyranose
H
OH
OH
H
-D-glucopyranose
Because of the tetrahedral nature of carbon bonds,
pyranose sugars actually assume a "chair" or
"boat" configuration, depending on the sugar.
The representation above reflects the chair
configuration of the glucopyranose ring more
accurately than the Haworth projection.
Pyranose and Furanose forms
Hemiacetal,
Haworth
structure
Hemiketal,
Haworth
structure
Haworth Structure of Glucose
Draw Fischer, rotate 90o,
then form the hemiacetal
-anomer
-anomer
Haworth Structure of Fructose
Ribose and Deoxyribse
Haworth structures
Mutarotation of Fructose
Open
chain
form
Mutarotation of Glucose
-D-glucofuranose
~0.5%
-D-glucofuranose
~0.5%
Open
chain
Form
~0.003%
-D-glucopyranose
36%, D = 112o
-D-glucopyranose
63%, D = 18.7o
Observed rotation = 52.7o
Test and Extend Your Understanding
Q: Don’t make the mistake of thinking that left/right orientation of the critical –OH group
changes a D into an L sugar. To show this, what sugar would you form if C-5 on D-glucose
was oriented to the left instead of the right?
A: L-idose
Q: Are D-glucose and D-ribose isomers? If so, what term describes the relationship?
A: D-glucose and D-ribose are not isomers of one another because they have different chemical
formulas. To be considered a structural or stereoisomer, the two molecules must have the same
empirical formula but differ only in the positioning of the atoms.
Q: What is the relationship between D-glucose and D-fructose?
A: This is a tough call. Both have the same formula and both have a carbonyl functional group. Dglucose has an aldehyde as its functional group and D-fructose has a ketone. The two must, therefore,
be considered “structural isomers” and not stereoisomers.
Q: How many epimers are there of D-glucose? Of -D-glucose?
A: Two, D-mannose and D-galactose. -D-glucose has 3: -D-glucose, -D-mannose, -D-galactose.
Q: How many stereoisomers of a heptulose are possible? How many are D and how many
are L sugars? How many names will be needed for all the isomers? (hint: the name tells you
the structure of this sugar).
A: A heptulose is a 7 carbon keto sugar. Therefore, it has 4 chiral centers, which means the straight
chain form has 16 isomers; 8 are D and 8 are L, just like glucose. There will be 8 names needed.
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.
Glycosidic Bonds
The anomeric hydroxyl and a hydroxyl of another
sugar or some other compound can join together,
splitting out water to form a glycosidic bond:
R-OH + HO-R'  R-O-R' + H2O
E.g., methanol reacts with the anomeric OH on
glucose to form methyl glucoside (methylglucopyranose).
H OH
H OH
H2O
H O
HO
HO
H
H
H
+
CH3-OH
H O
HO
HO
H
OH
H
OH
-D-glucopyranose
methanol
H
OH
OCH3
methyl--D-glucopyranose
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).
6 CH2OH
6 CH2OH
H
4
5
O
H
OH
OH
3
H
H
H
H
1
4
4
OH
5
H
OH
H
OH
maltose
H
H
1
OH
OH
6 CH2OH
H
H
1
O
4
5
O
H
OH
H
H
3
H
2
3
O
H
OH
O
O
2
6 CH2OH
H
5
2
OH
3
cellobiose
H
2
OH
1
H
OH
Cellobiose, a product of cellulose breakdown, is the
otherwise equivalent  anomer (O on C1 points up).
The (1 4) glycosidic linkage is represented as a zigzag, but one glucose is actually flipped over relative to
the other.
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).
The full name of sucrose is -D-glucopyranosyl(12)--D-fructopyranose.)
 Lactose, milk sugar, is composed of galactose &
glucose, with (14) linkage from the anomeric
OH of galactose. Its full name is -D-
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
H
O
OH
2
OH
H
OH
H
OH
H
OH
amylose
Polysaccharides:
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.
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
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 glucose
release from glycogen stores, e.g., in muscle during
exercise.
The ability to rapidly mobilize glucose is more
essential to animals than to plants.
CH2OH
H
O
H
OH
H
OH
H
1
O
H
H
OH
6CH OH
2
5
O
H
4 OH
3
H
H
H 1
2
OH
O
O
H
OH
CH2OH
CH2OH
CH2OH
H
H
O
O
H
OH
H
OH
O
H
O
H
OH
H
OH
H
H
OH
cellulose
Cellulose, a major constituent of plant cell walls, consists of
long linear chains of glucose with (14) linkages.
Every other glucose is flipped over, due to  linkages.
This promotes intra-chain and inter-chain H-bonds and
van der Waals interactions, that
cause cellulose chains to be
straight & rigid, and pack with a
crystalline arrangement in thick
bundles - microfibrils.
See: Botany online website;
website at Georgia Tech.
OH
H
H
H
H
H
Schematic of arrangement of
cellulose chains in a microfibril.
CH2OH
H
O
H
OH
H
OH
H
1
O
H
H
OH
6CH OH
2
5
O
H
4 OH
3
H
H
H 1
2
OH
O
O
H
OH
CH2OH
CH2OH
CH2OH
H
H
O
O
H
OH
H
OH
O
H
O
H
OH
H
OH
OH
H
H
H
H
H
H
H
OH
cellulose
Multisubunit Cellulose Synthase complexes in the plasma
membrane spin out from the cell surface microfibrils consisting
of 36 parallel, interacting cellulose chains.
These microfibrils are very strong.
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.
Explore and compare structures of amylose & cellulose using
Chime.
CH 2OH
D-glucuronate
6COO
H
4
6

5
H
OH
3
H
H
2
OH
1
H
H
OH
O
O
H
4
O
H
5
3
H
2
1 O
H
NHCOCH 3
N-acetyl-D-glucosamine
hyaluronate
Glycosaminoglycans (mucopolysaccharides) are linear
polymers of repeating disaccharides.
The constituent monosaccharides tend to be modified, with
acidic groups, amino groups, sulfated hydroxyl and amino
groups, etc.
Glycosaminoglycans tend to be negatively charged,
because of the prevalence of acidic groups.
CH 2OH
D-glucuronate
6

6COO
H
4
5
H
OH
3
H
H
2
OH
1
H
H
OH
O
O
H
4
O
H
5
3
H
2
1 O
H
NHCOCH 3
N-acetyl-D-glucosamine
hyaluronate
Hyaluronate (hyaluronan) is a glycosaminoglycan
with a repeating disaccharide consisting of 2 glucose
derivatives, glucuronate (glucuronic acid) & N-acetylglucosamine.
The glycosidic linkages are (13) & (14).
core
protein
heparan sulfate
glycosaminoglycan
transmembrane
-helix
cytosol
Proteoglycans are glycosaminoglycans that
are covalently linked to serine residues of specific
core proteins.
The glycosaminoglycan chain is synthesized by
sequential addition of sugar residues to the core
protein.
Some proteoglycans of the extracellular matrix
bind
non-covalently to hyaluronate via protein
domains called link modules. E.g.:
• Multiple copies of the aggrecan proteoglycan
associate with hyaluronate in cartilage to form
large complexes.
• Versican, another proteoglycan, binds
hyaluronate in the extracellular matrix of loose
connective tissues.
Websites
on:
Aggrecan
Aggrecan &
versican.
CH 2OH
D-glucuronate
6

6COO
H
4
5
H
OH
3
H
hyaluronate
H
2
OH
1
H
H
OH
O
O
H
4
O
H
5
3
H
2
1 O
H
NHCOCH 3
N-acetyl-D-glucosamine
N-sulfo-glucosamine-6-sulfate
iduronate-2-sulfate
CH2OSO3
H
H
COO
OH
O
O
H
O
H
H
OH
H
H
H
H
OSO3
O
H
NHSO3
heparin or heparan sulfate - examples of residues
Heparan sulfate is initially synthesized on a
membrane-embedded core protein as a polymer of
alternating
N-acetylglucosamine and
glucuronate residues.
Later, in segments of the polymer, glucuronate
residues may be converted to the sulfated sugar
iduronic acid, while N-acetylglucosamine residues
Heparin, a soluble glycosaminoglycan
found in granules of mast cells, has a
structure similar to that of heparan
sulfates, but is more highly sulfated.
PDB 1RID
When released into the blood, it
inhibits clot formation by interacting
with the protein antithrombin.
heparin: (IDS-SGN)5
Heparin has an extended helical
conformation.
C O N S
Charge repulsion by the many negatively charged
groups may contribute to this conformation.
Heparin shown has 10 residues, alternating IDS
(iduronate-2-sulfate) & SGN (N-sulfo-glucosamine-6sulfate).
Some cell surface heparan
sulfate glycosaminoglycans
remain covalently linked to
core proteins embedded in
the plasma membrane.
core
protein
heparan sulfate
glycosaminoglycan
transmembrane
-helix
cytosol
 The core protein of a syndecan heparan sulfate
proteoglycan includes a single transmembrane helix, as in the simplified diagram above.
 The core protein of a glypican heparan sulfate
proteoglycan is attached to the outer surface of the
plasma membrane via covalent linkage to a modified
phosphatidylinositol lipid.
Proteins involved in signaling & adhesion at the cell
surface recognize & bind heparan sulfate chains.
E.g., binding of some growth factors (small proteins)
to cell surface receptors is enhanced by their binding
also to heparan sulfates.
Regulated cell surface Sulf enzymes may remove
sulfate groups at particular locations on heparan
sulfate chains to alter affinity
for signal
proteins, e.g.,
N-sulfo-glucosamine-6-sulfate
iduronate-2-sulfate
CH OSO
H
growth factors.
O
O
2
H
Diagram
by Kirkpatrick &
Selleck.

H
H

COO
OH
3
O
H
H
OH
H
H
H
OSO3
O
H
NHSO3
heparin or heparan sulfate - examples of residues
Oligosaccharides
that are covalently
attached to proteins
or to membrane lipids
may be linear or
branched chains.
C
CH2OH
O
H
H
OH
O
CH2
CH
NH
H
O
serine
residue
O H
OH
H
HN
C
CH3
-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
-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.
NAN
NAN
NAN
Gal
Gal
Gal
NAG
NAG
NAG
Man
Man
Man
Key:
NAG
NAG
Asn
N-linked oligosaccharide
Fuc
NAN = N-acetylneuraminate
Gal = galactose
NAG = N-acetylglucosamine
Man = mannose
Fuc = fucose
Additional monosaccharides are added, and the Nlinked oligosaccharide chain is modified by removal
and addition of residues, to yield a characteristic
branched structure.
Many proteins secreted by cells have attached N-linked
oligosaccharide chains.
Genetic diseases have been attributed to deficiency of
particular enzymes involved in synthesizing or modifying
oligosaccharide chains of these glycoproteins.
Such diseases, and gene knockout studies in mice, have
been used to define pathways of modification of
oligosaccharide chains of glycoproteins and glycolipids.
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.
Lectins are glycoproteins that recognize and bind to
specific oligosaccharides.
Concanavalin A & wheat germ agglutinin are plant
lectins that have been useful research tools.
The C-type lectin-like domain is a Ca++-binding
carbohydrate recognition domain in many animal lectins.
Recognition/binding of CHO moieties of glycoproteins,
glycolipids & proteoglycans by animal lectins is a factor
in:
• cell-cell recognition
• adhesion of cells to the extracellular matrix
• interaction of cells with chemokines and growth factors
• recognition of disease-causing microorganisms
• initiation and control of inflammation.
Examples of animal lectins:
Mannan-binding lectin (MBL) is a glycoprotein
found in blood plasma.
It binds cell surface carbohydrates of diseasecausing microorganisms & promotes
phagocytosis of these organisms as part of the
immune response.
Selectins are integral proteins
of mammalian cell plasma
membranes with roles in
cell-cell recognition &
binding.
selectin
lectin domain
outside
The C-type lectin-like domain
transmembrane
is at the end of a multi-domain
-helix
cytosol
extracellular segment
cytoskeleton
binding domain
extending out from the cell
surface.
A cleavage site just outside the transmembrane -helix
provides a mechanism for regulated release of some
lectins from the cell surface.
A cytosolic domain participates in regulated interaction
with the actin cytoskeleton.
Lipids
 Lipids are molecules that consist of long
hydrocarbon chains. Attaching the three
chains together is usually a glycerol
molecule. Lipids are NONpolar.
Saturated vs. Unsaturated
Fat

Proteins
 Proteins are building blocks of structures
called amino acids. Proteins are what
your DNA codes to make (we will talk
about this in great detail in a month or
so).
 A peptide bond forms between amino
acids by dehydration synthesis.
Levels of Protein
Structure

Protein Structure
Level
Primary
Secondary
Description
The amino acid
sequence
Helices and Sheets
Disulfide bridges
Tertiary
Quaternary
Multiple polypeptides
connect