Introduction to Cellular Biology and Biochemistry PDF

Introduction to Cellular Biology and Biochemistry: 1-12: Small, Atoms 13-24: Metabolism 25-36, cells Labs start next monday Bring a lab coat and safety glasses Tests: Mid-term test 1 22 of April(15%) In person from 7-8 pm Online lecture tests (24%) Weekly online, open book tests, short multiple-choi...

Introduction to Cellular Biology and Biochemistry: 1-12: Small, Atoms 13-24: Metabolism 25-36, cells Labs start next monday Bring a lab coat and safety glasses Tests: Mid-term test 1 22 of April(15%) In person from 7-8 pm Online lecture tests (24%) Weekly online, open book tests, short multiple-choice questions Final Exam (30%) 2 hours Labs (31%) There will be 7 weeks of labs, with assessment including online tests and grading of lab material. (Check out the learn site) Contains pdfs of lecture sites and recordings of lectures. Grades will also be found there Online open access textbook, there are also first year biology text books in the library. Use a slightly harder to read font in order to interpret information better. Slightly harder to read fonts help you to retain more information while studying. Topic 1: introduction to the philosophy of science Topic 2: a recap of biochemistry and biomolecules Topic 3: Life needs energy Topic 4: Life is ordered Topic 5: Life requires the expression and transmission of genetic information What is life? Move Respiration Sensing Cells Growth Reproduction Excreting Nutrition Something that transforms energy, takes chemical energy and uses it to make order. First law of thermodynamics: Energy can be transferred or transformed, but not created or destroyed. :Chemical (food) — Mechanical, electrical, heat Second law of thermodynamics: Every energy transfer or transformation increases the disorder of the universe. Cells are the smallest unit of leaving systems Inside of them we have, lipids (energy, structure cell wall), proteins (doing things, structure), carbs (energy, structure), nucleic acid (Information, DNA and RNA) Viruses are living while inside of a cell but not living while outside of the cell. Since there is no exchange with the environment. Even still we see that the virus has a lipid membrane, proteins, carbs, RNA. Structure and shape is important for what they do. We have receptor proteins. The Ace2 receptor is an example of one of these found in our lungs, this receptor fits perfectly with the spike protein of the coronavirus. If you have had the virus before then you can build antibodies, Y shaped things that protect the receptor. As the strain of the virus evolves we can see there are mutations occurring in the spike protein, potentially allowing the virus to bond past antibodies or bond more effectively. Day 2: Discovery (inductive) reasoning describes nature: Analysing large volumes of data with the goal of finding patterns Hypothesis science: Making a prediction and capturing data to prove/reject the hypothesis. The scientific method: Observation/question→Research topic area (google)→Hypothesis→Test with experiment→analyse data→report conclusion→link back to the observation. To make a drug we want something with high affinity (low concentration) selectivity (no side effects), stability (how often/how long it lasts for/stable). Fox glove were used to treat Dropsy (congestive Heart failure). It was not known how it worked but now through science we have been able to remove the compounds that help to treat Dropsy. This way we are able to treat the disease and remove the compounds in the plant which cause side effects. Making the drug more efficient. Drugs like taxol started off as just using the tree bark from Pacific Yew bark. Rather than just searching for a bunch of random cures we use a hypothesis. Influenza was seen to bond to salicylic acid in the body Serendipity, Alexander Fleming made the first antibiotic by accident. He left a petri dish out overnight and when he returned noticed that mould had grown. He noticed that the bacteria was not growing close to the mould in his petri dish. From this he hypothesised that the mould must have some antibacterial properties. This was eventually confirmed and was used to make penicillin. Around the end of WW2 mass production of penicillin began largely due to the large number of soldiers dying from bacterial infections. This discovery was made almost entirely due to dumb luck but became one of the most incredible scientific discoveries. Should you believe everything you read on the interweb? You cannot always believe it as studies may show small improvements but unless these improvements are significant it is hard to say for certain that it causes a substantial change. Placebos are a great thing, especially when doing trials. A lot of the time when you give someone a tablet, even if it is just glucose people tend to say they feel better even if the tablet does not truly benefit them in any way. When testing drugs using placebo medication alongside the true medication being studied is good. This way you can work out if people are feeling better due to the placebo of taking a tablet or if they are feeling better because the medicine does actually positively affect them. This way you can test a whole lot of different areas and see if there are significant differences between the people taking the true medication and those taking the placebo medication. Placebo medication is used as a control because it truly does nothing to help people. Discovery science can be used in instances like testing to see if mask wearing is efficient. You can use a survey and ask people, if they wore a mask, and if they got sick. The only problem with this is it is much harder to implement a control and exclude variables. People who wear masks may stay home more and abide by social distancing rules while non mask wearers may not. In Biochemistry we only tend to look at a select few of the elements on the periodic table. O Oxygen C Carbon H Hydrogen N Nitrogen Atomic numbers are the number of electrons the element has, two in the first shell and then up to 8 in the second shell. Noble gases are very stable, as their shells are full with electrons. Elements with only one valence electron are very reactive since they are very keen on getting rid of that one electron they need to get rid of. Elements share electrons in order to complete their outer shell. Like H2O with two hydrogen atoms bonding onto one Oxygen atom since they all want to complete their outer shell. Carbon is known as the backbone of life because it is able to bond onto four things. This means it can bond with many different atoms. Electrons spend more time with the oxygen then they would with the hydrogen giving oxygen a slightly negative charge and giving hydrogen a slightly positive charge. Polar and nonpolar bonds Water is polar (it has two polar bonds) Alcohol is mostly nonpolar but has polar OH bond at the end. Ions are things that have gained or lost an electron while going through. Sodium loses an electron giving it a positive charge (a cation). Chlorine gains an electron giving it a negative charge (an anion). PH is a measure of the Hydrogen ion concentration. An acid is a substance that increases the hydrogen ion concentration. A base is a substance that decreases the hydrogen ion concentration. Sometimes it is good to have bonds that can be easily broken and reformed Covalent bonds take a lot of energy to form and a lot of energy to break. The hairs on a lizard's feet have Van der Waals interactions from uneven charge distributions. Atoms like to be a particular distance apart, the Van der Waals interaction is more similar to velcro than super glue. By itself they are not a very strong bond but together they are fairly strong. Hydrogen bonds occur when hydrogen is attached to an electronegative atom. There are hydrogen bond donors and hydrogen bond acceptors. The one with the hydrogen attached is the donor and the one without the hydrogen attached is the acceptor. Adhesion is when water sticks to the surface and cohesion is when water sticks to itself. Water is constantly breaking its bonds and re forming them, when water becomes ice, it is much more ordered. The water molecules are more spaced apart making it less dense meaning that it floats on top of water. When we heat water, we are breaking hydrogen bonds and it takes a lot of energy to do so. Ionic bonds are where one of the atoms takes a valence electrons away from the other Covalent bonds are when the two atoms share two valence electrons If they are polar then they are in a constant fight for the electron meaning that, one of the atoms may be slightly negative where the other may be slightly positive. Oxygen tends to be polar, whereas other atoms tend to be nonpolar for different reasons. heat is absorbed when hydrogen bonds break Heat is released when hydrogen bonds form. When dealing with liquid it is much easier to move things around. You cannot do this with solids. Salt dissolves in water because the cation Na becomes surrounded by O atoms because they are slightly negatively charged. Cl is an anion so it becomes surrounded between H atoms because H is slightly positively charged. Water is polar Ethanol is partly polar meaning it CAN dissolve in water. Hydrophilic: having a tendency to mix with water Hydrophobic: water fearing, molecules that repel from water. They do not mix with water because water is polar and they are non-polar Even large molecules such as proteins can be dissolved in water when H2O surrounds the protein and helps to break it down. Diffusion (nature hates gradients) Diffusion is the net movement of molecules or atoms from a region of high conc. to a region of low conc. Osmosis is the movement water through a semipermeable membrane from a area of high water concentration to an area of low water concentration Hypertonic: very salty, the water in the cell tries to run out because it is, causing the cell to shrivel up. Isotonic: a bit salty Hypotonic: not salty enough means that water fills up the cell leading to the cell bursting. Synthesis and hydrolysis of polymers Creating polymers helps create order and complexity Second law of thermodynamics: there is a tendency towards disorder (maintaining order requires energy) If you make the thing in the image into a line it is easier to manage. H bond with N, O, F The effectiveness of the binding of covid to our spike protein and Ace 2 receptor depends on shape and chemical charges. Morphine has a similar shape to endorphins. The part that bonds onto endorphin receptors is a similar shape to that of endorphins. Lipids are hydrophobic, they do not mix with water because water is polar but lipids are nonpolar. Bent molecules tend to be liquids at room temperature. Day 4: Lipids: are non-polar meaning they are hydrophobic - Saturated fat = solid (usually animal) - Unsaturated = liquid (usually plant) - Saturated fats are correlated with raising LDL levels (bad cholesterol), and increased LDL levels are associated with heart disease. Discovery based study to prove this would be comparing countries with high intakes of saturated fats and seeing if their rate of LDL or heart disease levels are higher. If we had a hypothesis we could feed people high intakes of saturated fats and see if they develop heart disease. - - To find if something is an omega 3 fatty acid, the double bond needs to be three points away from the omega side. Triglycerides (TAGs) are made up of glycerol (a 3-carbon alcohol) and 3 fatty acids (a carboxyl group attached to a long carbon skeleton. Phospholipids consist of two fatty acids and a phosphate group attached to glycerol Lipids as signalling molecules Hormones such as estradiol and testosterone, are examples of lipids. They do not dissolve in water. Carbohydrates: hydrates of carbon We have a carbon with a water molecule attached to it. Carbohydrates are polar. Carbohydrates have a carbon backbone bonded to hydrogens and OH groups. Carbohydrates such as glucose can get up to 6 carbons. There are aldehyde sugars: ketone sugars: Carbohydrates are oftentimes drawn up in the long structures but in our bodies they sometimes curl up on themselves and form rings. In sugars the hydroxyl group being in the down position opposed to being in the up position makes the sugar much sweeter to us. Protons are: H+ If something is sour it is the high concentration of protons causing this Complex carbohydrates = polysaccharides (meaning lots of sugars) Linking glucose monomers forms starch. Polysaccharides are energy stores Plants use starch as an energy store which is stable but has a slow release, plants do not need to be running away from predators meaning they can survive on a slower release. Animals go for using glycogen which is less stable but has a faster release, this means that we can have more sudden bursts of energy. Cellulose is a structural polysaccharide, we end up excreting cellulose because we as humans are unable to break it down. - High conc of Na ions causes things to taste salty to us In everyday products there are sugars that bind together. Artificial sweeteners: You can use the discovery method to make a sweet artificial sweeteners A hypothesis method would be to look at the taste buds and receptors on the tongue and try to recreate what happens to us when sugar hits our taste buds. Many artificial sweeteners used today were created accidentally by mixing things in beakers, getting some on their hands, and then accidentally licking their fingers. They were found by serendipity These can potentially be hundreds of times sweeter than actual sugars. Proteins: A chain made up of amino acids joined by peptide bonds that form a specific 3D structure What are amino acids? There are 20 different amino acids that have different functionalities giving proteins distinct functions and structures. There polar amino acids and non-polar amino acids Note: You will have to be able to look at the structure of amino acids and be able to tell if it is polar, non-polar, or basic, etc. Some amino acids are non essential because we are able to make them ourselves in our bodies. Other amino acids are essential because we cannot make them ourselves but they are necessary for us. Studies have shown that if we miss out on some of these essential amino acids the results can be very dangerous for people. On an amino acid there is an amino end and an acid end. These can be linked through peptide bonds. In these bonds the amino end needs to be linked to the acid end because the acid end can link to the acid end and the amino end can't link to the amino end. Alpha helices are the three dimensional shapes of proteins. There is the spiral going around in a circle (the backbone) with hydrogen bonds holding Beta sheets: - There are parallel and antiparallel sheets - Parallel all of the amino acids are pointing the same way Antiparallel they alternate which direction they are pointing in, (the first is pointing up, the second is pointing down, the third is pointing up, the fourth is pointing down) In a tertiary protein structure we can see a combination of alpha helices and beta sheets. Quaternary structure It takes a lot of energy to renature proteins. Enzymes: speed up chemical reactions, they are substrate specific and are reaction specific. Amino acids hold substrates in place in order to allow for reactions to start occurring. Heat hair straighteners break H bonds Perm - thiol groups - form covalent bonds. Nucleic acids A chain made up of nucleotides joined by phosphodiester bonds that form specific 3D structures. DNA and RNA are the most popular. Lecture 8: Lipids are the main energy source in our body, They can be packed together because they are hydrophobic. We can store our energy as glycogen and fat. Our brain relies almost entirely on glucose, our heart also tends to use glucose as an energy source. The rest of our body tends to break down lipids as an energy source - Lipids require more O2 to be broken down Carbohydrates require less O2 to be broken down When you hit a wall it is likely due to burning up all the glycogen in your muscles, this makes you feel like RUBBISH. Any time we lose weight we are breathing out as CO2. - In sprinting you are mainly relying on muscle ATP as fuel, (you are not exercising for enough time to burn fat) When doing long distance running you tend to use glycogen Amylase enzyme is an enzyme that can break starch into glucose. Bacteria are - prokaryotes Plant and Animal cells are - Eukaryotes Prokaryotes tend to be smaller than Eukaryotes In cells there is a large focus on surface area. Eukaryotic cells have internal membranes that compartmentalise their functions. Many different molecules come together inside of a cell, they are more like jelly because they are filled with proteins and molecules. There are big barriers on the outside of the cell, for a good barrier we want to keep the watery bit in and keep other things out. This hydrophobic barrier keeps some fluids from entering and leaving but allows for O2 and CO2 to diffuse out. When the barrier is made of unsaturated fats they tend to be runny When the barrier is made of saturated fats they are not. Transport proteins allow polar molecules through the membrane. Sometimes we have small holes in the cell walls that allow for active transport. Since some things cannot diffuse through the barrier can get through small cat flap-like structures. This can move molecules against regular concentration gradients and discriminate against certain molecules by only letting something like water in but not iron. Carbohydrates provide strength and signals On the outside of the coronavirus structure there is a lipid bilayer and many spike proteins which can bond to things inside the body. Spike proteins also have carbs. The viral membrane fuses with our membrane in a process called endocytosis. It then inserts itself into our cell and empties its contents Washing your hands with soap helps to get rid of the Coronavirus, this is because Lecture 9: How do we store information: Important things we want in something that stores our information: - Durability - Redundancy (back ups) (just incase some of it gets damaged there is more of it stored somewhere else) - Having a high capacity - Cost (in terms of energy) How will we retrieve the information How can we access it Is it universal How can we make a copy, how accurate will that copy be What is the speed that we can make the copy in Is it easy to find How much information do we store: Some organisms keep only the bare essentials Some organisms keep everything This is why some have a lot of energy worth of storage and others do not have that much. Bacterial DNA can store things very well and very efficiently. The entirety of the world's data can be stored in a kilogram of DNA. The Central Dogma is the flow of information DNA—> RNA—->Protein Each of our cells has around two metres worth of DNA inside of them. Enzymes: - DNase (an enzyme that breaks down DNA) - RNase (an enzyme that breaks down RNA) - Protease (an enzyme that breaks down protein) DNA is made up out of this. The bases are hydrophobic The phosphates and sugar are hydrophilic The hydrophobic base is found on the inside of the double helix with the hydrophilic sugar-phosphate backbone wrapped around the base. A always binds with T forming two hydrogen bonds C always binds with G with three hydrogen bonds Rosalind Franklin's contribution to the discovery of the DNA structure. Lecture 10: Lecture 11: DNA: is more stable RNA: is less stable Why use RNA, why not use DNA directly as a template. If we have one strand of DNA, we can amplify the signal by using one DNA strand; you can copy it into multiple different RNA strands. These can then be used to then make proteins. If we don't have proteins we don't need RNA. DNA can amplify the signal and also turn off the signal. DNA is the original building plans and RNA are a copy of the building plans. We don't want to take DNA to the building site because why take it when you can use a copy. RNA and proteins are constantly made and degraded. RNases are enzymes that break down RNA. E Coli RNA lasts five minutes before dying. RNA in yeast last around one hour RNA in Humans lasts hours to days. Proteins last hours. There are several different types of RNA - mRNA: messenger RNA (4%) - rRNA: ribosomes RNA (85%) - tRNA: transport RNA (10%) Percentages are how often they occur in our body Transcription is the DNA-directed synthesis of RNA Initiation of gene expression: How do we start? 1. A eukaryotic promoter: Promoter - DNA sequence 2. Several transcription factors bind to DNA, we get an alpha helix, with side chains that interact with the bases as they go through. They know where to start transcription Elongation of the RNA strand RNA polymerase adds RNA nucleotides, we do not need a primer for this one. This does makes it so that the RNA makes little mistakes for the mRNA but it doesn't really matter because it is not the main blueprint and its life span is not that long. Interesting: The poison in death cap mushrooms blocks our RNA polymerase which means that you can no longer make RNA. This means you eat the meal, feel fine, the next day feel fine, then you start feeling it because you are unable to make new proteins and you are starting to lose proteins inside of your body. Termination of elongation: We need a stop sign to signal the end of the elongation of the strand. Specific sequences trigger dissociation of the RNA polymerase. Rho protein is a Rho terminator, it starts moving along the chain, if it goes through As and Ts it moves along quickly and if it moves through Cs and Gs then it moves a lot slower since they are harder to break through. Processing of transcript: Eukaryotes are found in the region that includes protein-coding segments The sup is in the region of the 5 cap ends Exons express information, introns are in between Exons. We can remove introns and make it so that all of the exons are pushed together. The way we splice proteins can lead to getting different enzymes. Amino Acids have about 20 letters per amino acid. (letters are bases) When we read genetic code we read in the 5 prime to 3 prime direction. You cannot read it in reverse or you will get completely different information. The genetic code translates nucleotides into amino acids: Genetic code is unambiguous, all codons have meaning The code is degenerate The code is ordered - Pyrimidines Purines tRNA is the adaptor molecule: It provides our link between nucleic acids and amino acids. Anticodon are nucleic acids We need to match the correct amino acid Amino acid and a tRNA molecule binds onto tRNA synthesis RIbosomes are the machinery involved in protein synthesis Lecture 12: TransCription comes before transLation: C comes before L in the alphabet tRNA: have - an anticodon so they know where on the RNA they should place the amino acid - an amino acid that will be added to a peptide chain Ribosomes have three binding sites: - a site where we have an amino acid coming in - A site where protein is made - And one where they exit Correct binding is required for the right reading frame Small ribosomal subunit binds to mRNA Large ribosomal subunit Polypeptide chain is a chain of amino acids. (connected by peptide bonds) When we add amino acids together they always join onto the carboxyl group, Termination of protein synthesis: - Stop codon Mutations can affect protein structure and function: Mutations are changes in the genetic material from replication errors or DNA damage UV radiation can cause thymine dimers. If we have two thymines side by side in our DNA the UV light might cause covalent linkages. UV can cause more mutations in our DNA Small scale mutations include substitutions (substitutes a base for another base) or insertions as deletions (completely deletes a base). Many mutations are associated with disease Our hemoglobins are surrounded by water so it makes sense to put all of the hydrophilic amino acids on the surface and hydrophobic ones on the inside. Sickle cells are unable to properly carry oxygen. Sickle cells actually protect us against malaria to some extent since malaria attacks your red blood cells. Covid mutations: If we get a deletion of 2 amino acids we know that it must be due to 6 nucleotides deleting it. There was medication that could treat covid but it did it by reducing the accuracy of the RNA polymerase. This worked against covid but they stopped using it because it increased the chance of Covid mutating. This was obviously a bad thing because it means covid can potentially evolve at a quicker rate which could lead to problems. Can't cut its polyprotein up How to make a vaccine: