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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 GEK1530 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 GEK1530 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 GEK1530 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 GEK1530 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 GEK1530 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 GEK1530 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 GEK1530 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 GEK1530 Biological Membranes 37 GEK1530 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