GEK1530

GEK1530 Nature’s Monte Carlo Bakery:The Story of Life as a Complex System Frederick H. Willeboordse frederik@chaos.nus.edu.sg

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

The Bakery Water Yeast Flour Get some units - ergo building blocks AddIngredients mix n bake Get something wonderful! Process Knead Wait Eat & Live Bake

Flour Thus far, we’ve discussed: Carbohydrates 66 Water 11 Fiber 10 Protein 9 Fat 2 Ash 2 Let us now look at fibers

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? !

Glucose Building Blocks Six Carbon Sugar CH2OH H 6 O In aqueous solution C O C 1 5 H H OH C H H 2 C C HO H C 4 1 H Aldehyde group O OH 3 H OH OH H OH C C C C 4 1 H OH C 2 3 H OH C H OH 5 2 H OH C HO H C 6 Glucose 3 H H OH C 4 Hydroxyl group H OH C 5 CH2OH 6

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 R1-C(=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.

Glucose Chains Starch  a - linked Cellulose  b - linked

Proteins The last major ingredient of flour is proteins Carbohydrates 66 Water 11 Fiber 10 Protein 9 Fat 2 Ash 2 Usually we think of proteins as meat. But proteins are essential for all cells.

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)

H N O C S Amino Acids Amino Acids only contain five! Elements: O - Oxygen S – Sulfur H – Hydrogen C – Carbon N – Nitrogen

H O N H C H O Amino Acids Structure Amino Acids have a well defined structure and are built up of 3 parts. PolarÞ solubleOften looses the H+Þ becomes negatively charged acid A carboxyl group PolarÞ solubleOften gains an H+Þ becomes positively charged base A amino group R A side chain 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

H N H O C H O Amino Acids Structure H C 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

Amino Acids Electrostatics The side chains can be polar, non-polar and ionic (i.e. charged). R Charged Non-polar Polar CH3 OH C Example Side Chain Ends NH3+ O- O Carboxyl -> Acidic Amino -> Basic Methyl Hydroxyl

Amino Acids Chime

H H H N N N H H H O O O C C C H H H O O O Amino Acids Peptide Bond Amino Acids can be joined together by a so-called peptide bond. Condensation of H2O R H C C H R R O H C C N C H H R Peptide Bond

H N H O C H O 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. R H O H H N C C N C C C O H H R R Peptide Bond Peptide Bond The number of amino acids in a polypeptide chain is usually between 40 and 500 (but fixed for each type of protein).

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.

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

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.

Fold & Modify Protein Folding There are four different levels of folding (organization): Primary structure The sequence of amino acids Consists of a sequence of a-helices and b-sheets Secondary structure The further folding of the secondary structure in three dimensions. Tertiary structure Formed when a protein consists of several polypeptide chains (each having its own tertiary structure) Quaternary structure

Fold & Modify Protein Folding Secondary structures: a-helix b-sheet

Fold & Modify Protein Folding Tertiary structure:

Fold & Modify Protein Folding Quaternary structure: Hemoglobin

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?

What is Life? One way to answer this question would be to require certain properties that we associate with living things. Obviously a bad choice. Many living thing do not have legs. For example: It must have legs It must have metabolism 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.

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.

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).

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?

O O H H O O C C H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H O H H .. O P C C N H - H H H O Phospholipids - Cephalin Glycerol Fatty acid Hydrocarbon chain H C H H C + Fatty acid replaced by phosphate group and nitrogen containing molecule H H C O H Cephalin = Phosphatidylethanolamine

Hydrophilic Head Fatty Acid PhosphoricAcid Glycerol Fatty Acid Long Hydrophobic Tails Amino Alcohol 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. Graphical representation of phospholipid

Phospholipids

Phospholipids - schematically Schematically, phospholipids can be drawn as The interesting thing is that phospholipids can form bi-layers where the hydrocarbon chains are represented as wiggly tails. ~5nm The properties of the bi-layer are rather different from those of its elements

Chime Bilayer Single Phospholipid

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 …

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.

Biological Membranes

In short Fatty Acids Cholesterol Proteins Phospholipids Triglycerides BiologicalMembranes Lipid Vesicles

Wrapping up Building Blocks Proteins Membranes Key Points of the Day Give it some thought 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

GEK1530

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GEK1530

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