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Transcript
Nature’s Monte Carlo Bakery:
The Story of Life as a Complex System
GEK1530
Frederick H. Willeboordse
[email protected]
1
Fibers, Proteins & Membranes
Lecture 2
In this lecture we continue our
quest for building blocks and see
how Fibers, proteins and
membranes are constructed.
2
GEK1530
The Bakery
Flour
Water
Get some units
- ergo building blocks
Add
Ingredients
mix n bake
Get something
wonderful!
Process
Knead
Yeast
Wait
Bake
Eat & Live
3
GEK1530
Flour
Thus far, we’ve discussed:
Carbohydrates
Water
Fiber
Protein
Fat
Ash
66
11
10
9
2
2
Let us now look at fibers
4
GEK1530
Fibers
The fibers found in flour consist of cellulose which is the
material that makes up the cell walls in plants (note cell walls –
i.e. cell membranes - in animals are made up of a different
material).
It is a long chain of glucose, or in other words, a polysaccharide.
But wait a moment! Didn’t we say that
starch is a polysaccharide made with
glucose monomers too?
!
5
GEK1530
Glucose Building Blocks
Six Carbon Sugar
H
CH2OH
6
O
C
H 2C
HO 3C
H 4C
H 5C
H 6C
H
C5
H
1
OH
H
OH
OH
OH
H
O
C
H 2C OH
HO 3C H
H 4C OH
H 5C OH
CH2OH
6
Aldehyde group
1
H
C4
OH OH
C3
H
O
H
C1
H OH
C2
OH
Glucose
Hydroxyl group
6
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a,b – D,L
Isomers
Isomers are molecules with the same
chemical formula but a different structure.
D- and L- sugars are mirror images of one another
and the designation is with respect to the asymmetric
carbon the furthest from the aldehyde or keto group.
(a ketone is a functional group where we have R1C(=O)-R2 instead of R1-C(=O)-H as in aldehyde)
a and b indicate whether the C1 hydroxyl
extends above or below the ring.
Note: Some isomers have unique names and others don’t.
7
GEK1530
Glucose Chains
Starch  a - linked
Cellulose  b - linked
8
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Proteins
The last major ingredient of
flour is proteins
Carbohydrates
Water
Fiber
Protein
Fat
Ash
66
11
10
9
2
2
Usually we think of proteins as meat. But proteins are essential
for all cells.
9
GEK1530
Proteins
Most of the dry mass of a cell consists of proteins. Proteins
fulfill a myriad of functions in a cell. Yet, they are built up of
relatively simple building blocks.
These building blocks are 20 types of amino acids (recently the
existence of 2 more amino acids in proteins has been reported)
Abbrev.
Full Name
Side chain type
Abbrev.
Full Name
Side chain type
A
Ala
Alanine
hydrophobic
M
Met
Methionine
hydrophobic
C
Cys
Cysteine
hydrophilic
N
Asn
Asparagine
hydrophilic
D
Asp
Aspartic acid
acidic
P
Pro
Proline
hydrophobic
E
Glu
Glutamic acid
acidic
Q
Gln
Glutamine
hydrophilic
F
Phe
Phenylalanine
hydrophobic
R
Arg
Arginine
basic
G
Gly
Glycine
hydrophilic
S
Ser
Serine
hydrophilic
H
His
Histidine
basic
T
Thr
Threonine
hydrophilic
I
Ile
Isoleucine
hydrophobic
V
Val
Valine
hydrophobic
K
Lys
Lysine
basic
W
Trp
Tryptophan
hydrophobic
L
Leu
Leucine
hydrophobic
Y
Tyr
Tyrosine
hydrophilic
10
GEK1530
Amino Acids
Amino Acids only contain five! Elements:
H – Hydrogen
H
C – Carbon
C
O - Oxygen
S – Sulfur
N – Nitrogen
O
S
N
11
GEK1530
Amino Acids
Structure
Amino Acids have a well defined structure and are built up of 3 parts.
A carboxyl group
O
C
H
A amino group
A side chain
OH
N
H
Polar  soluble
Often looses the H+  becomes negatively
charged acid
Polar  soluble
Often gains an H+  becomes positively
charged base
R
An acid is a substance that increases the concentration of Hydrogen (H+) ions in water
A base is a substance that decreases the concentration of Hydrogen (H+) ions in water
12
GEK1530
Amino Acids
Structure
H
H
H
C
N
O
C
OH
R
Amino group
Carboxyl group
The side chain R can be as simple as a Hydrogen atom or
more complicated as in arginine where it is:
NH
R=
CH2 CH2 CH2 NH
C
NH2
13
GEK1530
Amino Acids
Electrostatics
R
Polar
Example Side Chain Ends
The side chains can be polar, non-polar and ionic (i.e. charged).
CH3
Methyl
OH
Hydroxyl
C
O OCarboxyl
-> Acidic
NH3+
Amino
-> Basic
14
GEK1530
Amino Acids
Chime
15
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Amino Acids
H
H
N
Amino Acids can be joined together by a so-called peptide bond.
H
C
O
C
Condensation
of H2O
Peptide Bond
R
H
OH
H
N
H
H
N
R
C
C
H
R
H
C
O
OH
R
O
C N
C
H
H
O
C
OH
Peptide Bond
16
GEK1530
Polypeptide Chains
Chains
In this way amino acids can be made into long chains that
are called peptide chains when they have less than about
30-50 amino acids long and polypeptide chains otherwise.
H
H
N
H
C
R
R
C N
C
C
H H
N C
H
H
O
R
O
Peptide Bond
O
C
OH
Peptide Bond
The number of amino acids in a polypeptide chain is usually
between 40 and 500 (but fixed for each type of protein).
17
GEK1530
Proteins
Proteins are made up of one or more polypeptide chains
Proteins fold due to the interactions in the protein. The
hydrophobic side chain e.g. tend to cluster on the inside while
the hydrophilic chains are on the outside.
The way a protein folds is a direct consequence of the
sequence of its amino acids and occurs spontaneously (i.e. in
a self-organized manner).
The way it is folded has a strong influence on its biological
function.
18
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Proteins
So we see that in order to arrive at proteins we need to go
through several layers:
Hierarchy
Atoms
Sub-units
Amino Acids
Polypeptide Chains
19
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Fold & Modify
Protein Folding
Proteins are only effective when
folded correctly.
Eventually, how a protein can fold is
based on its amino acid sequence.
However, after the initial stage, it may have the help of
chaperone molecules.
What is essential here, is that this process is very robust.
20
GEK1530
Fold & Modify
Protein Folding
There are four different levels of
folding (organization):
Primary structure
The sequence of amino acids
Secondary structure
Consists of a sequence of a-helices
and b-sheets
Tertiary structure
The further folding of the secondary
structure in three dimensions.
Quaternary structure
Formed when a protein consists of
several polypeptide chains (each
having its own tertiary structure)
21
GEK1530
Fold & Modify
Protein Folding
Secondary structures:
a-helix
b-sheet
22
GEK1530
Fold & Modify
Protein Folding
Tertiary structure:
23
GEK1530
Fold & Modify
Protein Folding
Quaternary structure:
Hemoglobin
24
GEK1530
Yeast
Yeast is a unicellular fungus and thus a life-form.
In the absence of oxygen, yeast can extract energy from glucose
by the following reaction:
C6H12O6 (glucose) →2C2H5OH + 2CO2
Carbon dioxide
Ethanol (the alcohol in alcoholic drinks)
But what is life?
25
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What is Life?
One way to answer this question would be to require
certain properties that we associate with living things.
For example: It must have legs
It must have metabolism
Obviously a bad choice.
Many living thing do not
have legs.
This sounds much more
reasonable.
BUT!
Unfortunately, there are things that behave just as if they
had a ‘living’ metabolism, but these things are not alive.
26
GEK1530
What is Life?
What can be considered to have metabolism but not
life?
Fire!
I’m aliiiiive!
Atoms go in, change and go out. This process is essential for the survival to
the phenomenon. The overall phenomenon is constant (i.e. there is a flame)
for as long there is food (oxygen, fuel …). There even can be replication (one
fire can light another fire).
But obviously, we do not consider fire to be alive.
27
GEK1530
What is Life?
Is there a better way to describe what is life?
One could look at the properties that are required for a
population to evolve by natural selection.
Multiplication
Heredity
Mutation
For individuals of the population, the requirement should be made a bit less strict in
that at least the parents fulfill the above requirement (a mule e.g. cannot multiply).
28
GEK1530
Membranes
Nevertheless, it does seem to be reasonable to state that there
should be some separation between ‘inside’ and ‘outside’.
A nice cozy house to live in. (note: this is in an
out-of-equilibrium state compared to its
environment)
Let us go back to the fatty acid we discussed before. We saw
that a small change can give us soap. Are there other interesting
changes one can make?
29
GEK1530
Phospholipids - Cephalin
Glycerol
Fatty acid
HHHHHHHHHHHHHHHHH O H
HCCCCCCCCCCCCCCCCC COC H
Hydrocarbon chain
HHHHHHHHHHHHHHHHH
HHHHHHHHHHHHHHHHH O
HCCCCCCCCCCCCCCCCC CO C H
HHHHHHHHHHHHHHHHH
+H H O
Fatty acid replaced by
H
..
phosphate group and nitrogen
HNCC OPOC H
containing molecule
H H H O- H
Cephalin = Phosphatidylethanolamine
30
GEK1530
Phospholipids
Fatty Acid
Fatty Acid
Long Hydrophobic Tails
Glycerol
For phospholipids we can start with a fat too but in this
case one fatty acid is replaced by a phosphoric acid to
which an amino alcohol is attached.
Phosphoric
Acid
Amino Alcohol
Graphical representation
of phospholipid
31
GEK1530
Phospholipids
32
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Phospholipids - schematically
Schematically, phospholipids The interesting thing is that
can be drawn as
phospholipids can form bilayers
where the hydrocarbon
chains are represented as
wiggly tails.
~5nm
The properties of the bi-layer
are rather different from those
of its elements
33
GEK1530
Chime
Bilayer
Single Phospholipid
34
GEK1530
Phospholipids - Spatial Organization
Micelles
Vesicles
The bi-layer is semi-permeable,
H2O, e.g., can diffuse through.
Giant vesicles
can be larger
than 1 mm!
Hence again, we see that the
sum is different from the
elements so lets jump the gun
and draw some conclusions …
35
GEK1530
Towards biological bilayers
One important aspect of bilayers is their fluidity. In biological membranes the
bilayers are in a so-called liquid crystal state. That is to say, the overall structure
of the layer remains but individual phospholipids can move around inside the
layer.
As you may know, at room temperature, many fats are about to become solid but
clearly, a membrane of a living organism cannot be solid…
Similarly, at low enough temperatures, lipid bilayers can become crystalline.
Clearly, packing the hydrocarbon tails is easier when they are straight and
therefore one way to lower the temperature is to have tails with kinks. Kinks are
due to double bonds.
Another way is the insertion of other suitable molecules that disrupt the packing
of the tails. The main such molecule is cholesterol. Besides lowering the
temperature at which the bilayer becomes crystalline, cholesterol also reduces the
mobility of the phospholipids in the liquid crystal phase. Hence it makes a
membrane less fluid.
36
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Biological Membranes
37
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Biological Membranes
38
GEK1530
In short
Fatty Acids
Cholesterol
Triglycerides
Phospholipids
Lipid Vesicles
Proteins
Biological
Membranes
39
GEK1530
Wrapping up
Key Points of the Day
Give it some thought
Building Blocks
Proteins
Membranes
What is life?
Under the right circumstances, vesicles can form
spontaneously.
Consequently, a cellular environment is easily formed.
What else would one need for some kind of life?
References
http://www.cem.msu.edu/~reusch/VirtualText/carbhyd.htm
http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/sugar.htm
http://info.bio.cmu.edu/Courses/03231/BBlocks/BBlocks.htm
40