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GEK1530Frederick H. Willeboordsefrederik@chaos.nus.edu.sg

Nature’s Monte Carlo Bakery:The Story of Life as a Complex System

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Fibers, Proteins & Membranes

Lecture 2 In this lecture we continue our quest for building blocks and see how Fibers, proteins and membranes are constructed.

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The Bakery

AddIngredients

Process

Flour Water Yeast

Knead Wait Bake

Get some units - ergo building blocks

Eat & Live

Get something wonderful!

mix n bake

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Flour

Thus far, we’ve discussed: Carbohydrates 66Water 11Fiber 10Protein 9Fat 2Ash 2

Let us now look at fibers

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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? !

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OH HCC

OH

HHO C

OHH C

CH2OH

OHH CC

OH

HO COHH COHH C

H

1

2

3

4

5

1

2

3

5

6

Aldehyde group

Hydroxyl group

C

C

C

O

OH3

1

5

CH2OH6

OH

HH

H

Glucose

In aqueous solution

Six Carbon Sugar

Glucose Building Blocks

OHH C6

OHH C4

H C

OH4

H

COH

2

H

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Isomers are molecules with the same chemical formula but a different structure.

Isomers

– D,L

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 R1-C(=O)-R2 instead of R1-C(=O)-H as in aldehyde)

Note: Some isomers have unique names and others don’t.

and indicate whether the C1 hydroxyl extends above or below the ring.

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Glucose Chains

Cellulose - linkedStarch - linked

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Proteins

The last major ingredient of flour is proteins

Carbohydrates 66Water 11Fiber 10Protein 9Fat 2Ash 2

Usually we think of proteins as meat. But proteins are essential for all cells.

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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.

Proteins

Abbrev.Full Name Side chain type

A Ala Alanine hydrophobic

C Cys Cysteine hydrophilic

D Asp Aspartic acid acidic

E Glu Glutamic acid acidic

F Phe Phenylalanine hydrophobic

G Gly Glycine hydrophilic

H His Histidine basic

I Ile Isoleucine hydrophobic

K Lys Lysine basic

L Leu Leucine hydrophobic

Abbrev.Full Name Side chain type

M Met Methionine hydrophobic

N Asn Asparagine hydrophilic

P Pro Proline hydrophobic

Q Gln Glutamine hydrophilic

R Arg Arginine basic

S Ser Serine hydrophilic

T Thr Threonine hydrophilic

V Val Valine hydrophobic

W Trp Tryptophan hydrophobic

Y Tyr Tyrosine hydrophilic

These building blocks are 20 types of amino acids (recently the existence of 2 more amino acids in proteins has been reported)

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Amino Acids

Amino Acids only contain five! Elements:

H – Hydrogen

C – Carbon

N – Nitrogen

H

C

N

OO - Oxygen

S – Sulfur S

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Amino Acids have a well defined structure and are built up of 3 parts.

A carboxyl group

A amino group

A side chain

CO

HO

NH

H

Polar solubleOften looses the H+ becomes negatively

charged acid

Polar solubleOften gains an H+ becomes positively

charged base

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

Structure

R

Amino Acids

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CO

HON

H

H

R

C

H

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:

CH2 CH2 CH2 NH C

NH

NH2

Structure

Amino Acids

=

R

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The side chains can be polar, non-polar and ionic (i.e. charged).

RNon-polar

CH3

Exa

mpl

e S

ide

Cha

in E

nds

OH CO O-

NH3+

Carboxyl-> Acidic

Amino-> Basic

Pol

ar

Charged

Methyl Hydroxyl

Electrostatics

Amino Acids

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Chime

Amino Acids

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Amino Acids

Amino Acids can be joined together by a so-called peptide bond.

CO

HON

H

HR

C

H

CO

HON

H

H

R

C

H

Con

dens

atio

n o

f H

2OC

O

NH

HR

C

H

CO

HON

H

R

C

H

Peptide Bond

Peptide Bond

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Polypeptide 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.

C

O

NH

HR

C

H

C

O

N

H

R

C

H

Peptide Bond

N

H

CO

HOR

C

H

Peptide Bond

The number of amino acids in a polypeptide chain is usually between 40 and 500 (but fixed for each type of protein).

Chains

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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.

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So we see that in order to arrive at proteins we need to go through several layers:

Atoms

Sub-units

Amino Acids

Polypeptide Chains

Hierarchy

Proteins

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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.

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Protein Folding

There are four different levels of folding (organization):

Primary structure

Secondary structure

Tertiary structure

Quaternary structure

The sequence of amino acids

Consists of a sequence of -helices and -sheets

The further folding of the secondary structure in three dimensions.

Formed when a protein consists of several polypeptide chains (each having its own tertiary structure)

Fold & Modify

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Protein Folding

Secondary structures:

-helix

-sheet

Fold & Modify

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Tertiary structure:

Fold & Modify

Protein Folding

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Quaternary structure:

Hemoglobin

Fold & Modify

Protein Folding

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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

Ethanol (the alcohol in alcoholic drinks)

Carbon dioxide

But what is life?

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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 legsIt must have metabolism

Obviously a bad choice. Many living thing do not have legs.

This sounds much more reasonable.

Unfortunately, there are things that behave just as if they had a ‘living’ metabolism, but these things are not alive.

BUT!

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What can be considered to have metabolism but not life?

Fire!

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.

I’m aliiiiive!

What is Life?

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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

Mutation

Heredity

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).

What is Life?

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Membranes

Nevertheless, it does seem to be reasonable to state that there should be some separation between ‘inside’ and ‘outside’.

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?

A nice cozy house to live in. (note: this is in an out-of-equilibrium state compared to its

environment)

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H

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

OC

OH

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

OC

OH

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

C

C

C

H

H

H

HGlycerolFatty acidHydrocarbon chain

+

O

H..

-N C

OH

POC

OH

H H

H

HFatty acid replaced by phosphate group and nitrogen containing molecule

Phospholipids - Cephalin

Cephalin = Phosphatidylethanolamine

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Phospholipids

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.

Hydrophilic

HeadFatty Acid

Fatty Acid

Gly

cero

l

PhosphoricAcid

Amino AlcoholLong Hydrophobic Tails

Graphical representation of phospholipid

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Phospholipids

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The interesting thing is that phospholipids can form bi-layers

The properties of the bi-layer are rather different from those of its elements

Schematically, phospholipids can be drawn as

where the hydrocarbon chains are represented as wiggly tails.

~5nm

Phospholipids - schematically

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Chime

Bilayer Single Phospholipid

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Micelles Vesicles

The bi-layer is semi-permeable,H2O, e.g., can diffuse through.

Hence again, we see that the sum is different from the elements so lets jump the gun and draw some conclusions …

Giant vesicles can be larger than 1 m!

Phospholipids - Spatial Organization

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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.

Towards biological bilayers

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Biological Membranes

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Biological Membranes

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In short

Fatty Acids

TriglyceridesPhospholipids

Cholesterol

Proteins

Lipid VesiclesBiologicalMembranes

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Wrapping up

Building BlocksProteinsMembranes

Key Points of the Day

Give it some thought

References

What is life?

Consequently, a cellular environment is easily formed. What else would one need for some kind of life?

Under the right circumstances, vesicles can form spontaneously.

http://www.cem.msu.edu/~reusch/VirtualText/carbhyd.htmhttp://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/sugar.htm

http://info.bio.cmu.edu/Courses/03231/BBlocks/BBlocks.htm