Biochemistry Notes PDF

Lesson 1.1 - Chemical Fundamentals Molecule Shape Chemical Fundamentals ​ Molecules (lipids, nucleic acids, proteins, and carbohydrates) play big role in living things ​ The understanding of chemistry behind biologically import...

Lesson 1.1 - Chemical Fundamentals Molecule Shape Chemical Fundamentals ​ Molecules (lipids, nucleic acids, proteins, and carbohydrates) play big role in living things ​ The understanding of chemistry behind biologically important molecules is biochemistry Isotopes ​ When 2 atoms have same number of protons and electrons but different number of neutrons they are isotopes ○​ Atomic mass differs ​ In radioisotopes, nucleus in isotope spontaneously decays ​ Radioisotope has half-life ○​ Amount of time it takes for half of nuclei to decay Molecular Polarity ​ Used in radiometric dating and as radioactive tracers ​ To be considered polar molecule ○​ Contain polar covalent bonds ○​ Have asymmetrical arrangement of bonds (shape) Chemical Behaviour ​ Electrons move around atomic nucleus at distance determined by amount of energy electron has Water ​ Further it is from nucleus, greater its potential energy ​ Found around nucleus in energy levels ​ Polar molecule with many unique properties ○​ n=1 ​ Called universal solvent because of ability to dissolve many ionic and polar compounds ​ Electrons in outermost energy level are called valence electrons ​ Hydrogen bonding (strongest of intermolecular forces) gives water properties that support ​ Valence electrons determine chemical behaviour of atom life on earth Density of Water Chemical Bonding ​ Intramolecular forces (between atoms) ○​ Ionic and covalent bonds ​ Intermolecular forces (between molecules) ○​ Hydrogen bonds, hydrophobic interactions, and other weak forces Intramolecular Forces ​ Ionic bond is force of attraction between positive and negative charges ○​ E.g. Sodium Chloride (NaCl) ​ Since cell is aqueous environment are considered free, dissociated (Na+) since they dissolve in water Importance of Water – Solubility of Molecules in Cell ​ Water is key to life ​ Covalent bond forms when two atoms share one or more pairs of valence electrons ○​ Cells of living things operate in water environments ○​ E.g. Water (H2O) ​ Polar molecules will usually be soluble in water if they are not too complex ○​ Molecules are hydrophilic (water-loving) ​ Non-polar molecules are not soluble in water ○​ Molecules are hydrophobic (water-hating) Intermolecular Forces ​ Hydrogen bonding ○​ Weak force of attraction between slightly positive hydrogen atom and slightly negative charge on neighbouring molecule’s oxygen, nitrogen, or fluorine ​ Hydrophobic interactions ○​ Interactions resulting from tendency of nonpolar molecules to band together in water Intramolecular Forces – Polarity ​ Polar Covalent Bonds Biochemical Reactions ○​ Unequal sharing of electron pair results in one atom attracting pair more strongly than other atom ​ Neutralization ○​ Due to difference in electronegativity ​ Condensation ○​ Atoms will take on partial positive (δ +) or partial negative (δ -) charge ​ Hydrolysis ​ redox Neutralization Reaction Building Hydrocarbons ​ Acid and bases react to form water and salt ​ Compounds composed of H and C ○​ HCl(aq) + NaOH(aq) → H2O(l) + NaCl(aq) ​ Combinations of H and C form non-polar molecules, but store lots of energy ​ In order to be useful to living things, hydrocarbons need to be able to interact with water Acid How is this achieved ​ Substance that produces hydrogen ions when dissolved in water ○​ Since water is polar it attracts hydrogen ion ot make hydronium ion ​ At strong polar functional group to carbon backbone ​ E.g. hydrogen chloride (HCl) is gas ○​ Stearic acid has carboxyl functional group ○​ When mixed with water, it form hydrochloric acid ​ HCl(g) + H2O(l) → H3O+ + Cl- Functional Groups Base Buffers Group Chemica Structural formula Ball-and-stick model Found in l formula ​ Buffer – substance that helps reduce major pH level fluctuations ​ E.g. human blood operates best at pH of 7.4 (acceptable blood pH range: 7.35-7.45) ○​ Natural buffers in body able to maintain optimal pH levels by reacting to Hydroxyl —OH —OH Alcohols neutralize excess acid or excess base (e.g. ○​ Important buffer in human body (in blood and extracellular fluid) is ethanol) ​ Carbonic acid – Bicarbonate buffer system Carboxyl —COO Acids (e.g. H vinegar) Carbonic Acid – Bicarbonate Buffer System Amino —NH2 Bases (e.g. ammonia) Sulfhydryl —SH Rubber Phosphate —PO4 ATP ​ If blood becomes too basic ○​ CO2 and H2O in blood react to form carbonic acid (H₂CO₃) ○​ H₂CO₃ dissociates into bicarbonate ion (HCO₃-) and hydrogen ions (H+) to decrease blood pH ​ If blood becomes too acidic ○​ Excess hydrogen ions in blood will combine with bicarbonate ions to make more carbonic acid Carbonyl —COH Aldehydes ○​ Works to raise pH in two ways (e.g. ​ Carbonic acid is weak acid, which raises pH of blood formaldehy ​ Carbonic acid is converted to H2O and CO2 de) ​ As CO2 is expelled from body there is drive to make more carbonic acid in reaction —CO— ​ To make more carbonic acid, excess Ketones hydrogen ions in blood are used, raising pH (e.g. of blood acetone) Base ​ Substance that produces hydroxide ions when dissolved in water ​ E.g. sodium hydroxide (NaOH) is solid ○​ When mixed with water it forms base ​ NaOH(s)+H2O(l) → Na+ + OH- + H2O(l) Lesson 1.1b - The Chemicals of Life – Functional Groups as Linakes Organic Molecules React Why are organic molecules made out of carbon? Condensation Reaction (dehydration synthesis) ​ Carbon is able to form stable bonds with carbon atoms ​ Carbon is best electron sharer ​ Creates covalent bond (or linkage) between interacting functional groups ○​ Can form bonds with 4 other atoms ​ Energy is absorbed into new bond ○​ Bonds are covalent and therefore strong ​ Also called ANABOLIC reaction ○​ Strong bond holds energy ○​ Producing larger molecules from smaller subunits ​ Examples ○​ Monomers (smaller molecules) will combine to form (polymers) very large molecules through condensation reactions Hydrolysis Reaction (hydration) ​ Water molecule used to break covalent bond ​ Releases energy (bonds are broken) ​ Also called catabolic reaction break larger macromolecule into smaller subunits Common Biological Linkages ​ hydroxyl + hydroxyl ether ​ Dehydration Synthesis (Condensation Reaction) ○​ Two subunits link together through removal of water molecule ○​ Dehydration synthesis is anabolic reaction that absorbs energy ​ hydroxyl + carboxyl ester ​ amino + carboxyl amide (peptide) ​ Hydrolysis reaction ○​ Two subunits break apart through addition of water molecule ○​ Hydration synthesis is catabolic reaction that releases energy ​ phosphate + hydroxyl phosphate ester Lesson 1.3 - Macromolecules Nutrients ​ Humans eat to build their bodies, gain strength, for taste, to live, etc. ​ Food → ENERGY → allows us to do WORK ​ To be healthy, body requires approximately 50 nutrients Carbohydrates ​ Nutrients can be grouped into 3 broad categories ○​ vitamins/minerals ​ Used for energy, building material, and cell identification and communication ○​ Water ​ Contain carbon, hydrogen, and oxygen 1:2:1 ratio ○​ Macromolecules ​ Classified into 3 groups ​ Protein ○​ Monosaccharides ​ Carbohydrates ○​ Oligosaccharides ​ Fat (lipids) ○​ Polysaccharides ​ Nucleic acids Monosaccharides Macromolecules ​ Subunit of carbohydrate ​ Large molecules composed of repairing subunits ​ Two types ​ Four major classes: carbohydrates, proteins, lipids, and nucleic acids ○​ Aldose ​ All carbons have hydroxyl groups attached, with exception of carbonyl group found on terminal carbon  ​ Energy storage for plants ○​ Ketose ○​ Glycogen ​ All carbons have hydroxyl groups attached, with exception ​ Composed of α1-4 links but α1-6 links where it branches of carbonyl group found on central carbon ​ More branched than starch ​ Animal energy storage ​ When dissolved in water, sugars with 4 or more carbons form rings structures ​ When dry, they form linear structures ○​ Cellulose ​ Composed of ß1-4 links ​ Every other glucose subunit becomes inverted to accommodate link ​ Not coiled or branched ​ Used in plant cell walls ​ Cellulose structure Disaccharides ​ 2 subunits of simple sugars combine ​ Condensation reaction (dehydration synthesis) forms glycosidic linkage between two monosaccharides to make oligosaccharide ​ Maltose (α 1-4); Sucrose (α 1-2) ○​ Chitin ​ Cellulose-like polymer of N-acetylglucosamine ​ Monomer is glucose molecule with nitrogen containing group attached at second C position ​ Used in insect and crustaceans to form hard exoskeleton Polysaccharides ​ Many subunits (100’s to 1000’s) ​ Four types: starch, glycogen, cellulose, chitin ○​ Starch ​ Composed of amylose (α 1-4 links) and amylopectin (α 1-4 links but α 1-6 links where it branches) Lipids Steroids ​ Hydrophobic molecules ​ Hydroponic molecules ​ Generally nonpolar and are insoluble in water ​ Four fused hydrocarbon rings with several functional groups attached ​ Includes fats, phospholipids, steroids, and waxes ​ Cholesterol is converted, by body, into bile salts and vitamin D ​ Gram of fat stores 9 calories of energy ​ Other steroids include sex hormone ○​ Compared to 4 calories in carbohydrates and proteins ○​ E.g. estrogen, testosterone, progesterone ​ Used for energy storage, cushioning, and insulation ​ Animals convert excess carbohydrates into fat and store fat as droplets in cell od adipose (fat) tissue Fats ​ Fats (e.g. triglycerides) ○​ Backbone is glycerol which has 3 hydroxyls ○​ Each fatty acid has terminal carboxylic acid and between 16 and 18 carbons ○​ Condensation reaction attaches 3 fatty acids to glycerol making ester linkages (esterification) Waxes ​ E.g. beeswax, paraffin, cutin ​ Consists of alcohol or carbon rings with ester linkage to fatty acid Saturated Fats ​ Hydrophobic ​ Come from animals ​ Acts as waterproof coatings on various plant and animal parts ​ Used for long-term energy storage, insulation, protection, and helps dissolve fat soluble vitamins ​ No double bonds between carbon atoms in fatty acids ​ Solid at room temperature due to straight chains → fatty acids are closer together → more intermolecular forces Unsaturated Fats ​ From plant oils ​ One or more double bonds between carbon atoms in fatty acids ​ Double bonds form kinks, producing more space between fatty acids thus reducing number of intermolecular interactions Nucleic Acids ​ Liquid at room temperature ​ Found in DNA, RNA, ATP, and nucleotide coenzymes (NAD+, NADP+ and FAD) ​ DNA and RNA are nucleotide polymers Phospholipids ​ Nucleotides consist of nitrogenous base, five-carbon sugar and phosphate group ○​ Nitrogenous bases are ​ Composed of one glycerol, two fatty acids, and a highly polar phosphate group ​ Adenin A ​ Form cellular membranes (phospholipid bilayer) ​ Guanine G ​ Phospholipid bilayer is virtually impermeable to macromolecule, relatively impermeable ​ Cytosine C to charged ions, and quite permeable to small, lipid soluble molecules ​ Thymine T ​ O2 and CO2 diffuse through with very little resistance ​ Uracil U ​ In DNA, A bonds with T with 2 hydrogen bonds, and G bonds with C with 3 Hydrogen bonds ​ Two strands are antiparallel ○​ One strand is upside down compared to the others Nucleotides Nitrogenous Bases Polar Amino Acids Acid and Basic Amino Acids Sugars Protein Structure ​ Amino acids are monomers that make up proteins Proteins ​ Bonds that hold amino acids together are called peptide bonds ​ Peptide bonds are formed by dehydration synthesis reaction ​ Involved in almost everything cells do ​ Also called conformation ​ Can be enzymes, immunoglobulins, hemoglobin, keratin, fibrin, etc. ​ Depends on amino acids it contains, and interaction between those amino acids ​ Proteins are made up of many amino acids ○​ Each is called a residue Amino Acids ​ Proteins are made of one or more amino acids ​ 20 amino acids differ in R groups they contain ○​ 8 amino acids are essential ​ Side chains can make amino acid polar (hydrophilic), non-polar (hydrophobic), or charged (acidic/basic) Nonpolar Amino Acids Primary Structure ​ Polypeptide chain → many amino acids in chain connected by peptide bonds ​ Sequence of amino acids is determined by nucleotide sequence of a particular gene ​ In protein with X number of amino acids, number of possibilities is 20x  ​ NOT used up during reaction – can be used over and over again → catalytic cycle ​ Specific to particular substrate (reactant) ​ Classified according to type of reaction they catalyze ​ Named specifically for reaction they catalyze and usually end in “ase” How do Enzymes Work Secondary Structure ​ Lower activation energy of reaction ​ Folding and coiling of polypeptide chain as it grows ​ Formed by hydrogen bonds between oxygen atoms of carboxyl group and hydrogen atoms of amino group ​ Two types ○​ α helix – tight coil produced by H-bonds every 4 peptide bonds repeated ○​ ß pleated sheets – H-bonds formed between parallel stretches of a polypeptide How do Enzymes Lower Activation Energy Tertiary Structure ​ They form enzyme-substrate complexes ​ Polypeptide chain undergoes additional folding due to side chain (R-group) interaction ​ Substrates bind to a region on the surface of enzymes known as the active site, to form an enzyme-substrate complex ​ The active site undergoes a slight conformational change to better accommodate the substrate (induced fit) How does the enzyme-substrate complex lead to lowering activation energy? ​ In catabolic reactions the interactions between the substrate and enzyme causes stress or distorts the bonds in the substrate, allowing bonds to break Quaternary Structure ​ Two or more polypeptide chains come together, such as in collagen and hemoglobin ​ In anabolic reactions the enzyme stress or distorts bonds to encourage a link between two substrates to allow bonds to form between them Denaturation ​ Temperature and pH changes can cause protein to unravel ○​ Denature ​ Due to disruption hydrogen bonds, etc ​ Denatured protein is unable to carry out its biological function Lesson 1.4 - Enzymes What is an Enzyme ​ Protein catalysts that speed up biochemical reaction Factors that Affect Enzyme Activity Temperature ​ As temperature rises, reacting molecules gain more kinetic energy increases chances of successful collisions. ​ There, the rate of the reaction increases. ​ Eventually, at a set OPTIMAL temperature, the enzyme’s activity is at its greatest. E.g. In humans, the optimal temperature of all enzymes is 37ºC ​ As temperature increases, higher than the optimal temperature, the enzyme denatures. ​ Feedback inhibition ○​ A method used by cells to control metabolic pathways involving a series of reactions ○​ A product formed later in a sequence of reactions allosterically inhibits an enzyme that catalyzes the reaction earlier on pH ​ Enzymes work within a very small pH range ​ Optimal pH is the level at which an enzyme’s activity is the greatest ​ pH levels outside of the optimal range can cause denaturing of the enzyme Allosteric Regulation ​ Cells control enzyme activity to coordinate cellular activities ​ Activators may bind to allosterically controlled enzymes to stabilize its shape and keep all active sites available ​ Allosteric inhibitors may bind to allosterically controlled enzymes to stabilize the inactive form of the enzyme. Concentration of substrate and enzyme ​ The rate of reaction will increase with an increase of either substrate or enzyme concentration ​ However, with an increase in substrate concentration, eventually all of the active sites of the enzymes become occupied all at once (point of saturation). ​ Before any more reactions can occur an enzyme/substrate complex has to dissociate to free up an active site Cofactors and Coenzymes ​ Required by some enzymes to function ​ They bind to the active sites of enzyme ○​ Cofactors are inorganic, non-protein components, usually attract electrons in the substrate to assist in breaking bonds (Zn2+ and Mn2+) → Inhibition MINERALS. ○​ Coenzymes are organic, non-protein molecules, such as the derivatives of ​ Competitive Inhibitors are so similar to an enzyme’s substrate that they can bind to the many VITAMINS active site and block the normal substrate ​ They often shuttle molecules from one enzyme to another. ​ Non-competitive Inhibitors bind to the enzyme at an allosteric site (not the active site) (e.g. vitamin B3 is a coenzyme of NAD+) and cause a conformational change in the enzyme, preventing the normal substrate from binding  Lesson 2.1 - Introduction to Cells Prokaryotic Cell vs Eukaryotic Cell Cell Theory ​ All living things are made of one or more cells ​ Cell is functional unit of life ​ All cells come from pre-existing cells Cell Structural Support ​ Cell wall ○​ Plants, fungi, protists ○​ Composed of cellulose, chitin, other pectins Why are Cells so Small ​ Cells have to interact with surrounding environment ​ Need to take in nutrients and gases from blood stream ​ If cell was large, it would take nutrients and gases long time to get to various parts of cell and cell would not be able to carry on its everyday, regular functions ​ Cytoskeleton ○​ Fibers that extend throughout cytoplasm to anchor organelles and allow substances to move about ​ Like tracks Lesson 2.2 - The Cell Membrane and Transport Part 1 Types of cells ​ Bacterial ​ Plant ​ Animal ​ All cell contain ○​ Genetic material (DNA) ○​ Cell membrane ○​ Cytoplasm The Plasma (Cell) Membrane ​ Gate-keeper and declares address of cell to all other cells and rest of body ​ The most important part of cell with regards to cell’s interaction with environment around it ​ Cell membrane is made up of phospholipid bilayer  Proteins in Bilayer ​ Helps stabilize the membrane by holding them in place ​ Other functions ○​ Transport (channel/integral proteins): allow molecules to enter/leave through the membrane ​ Passive transporters (do not require energy) ​ Active transporters (do require energy in the form of ATP ○​ Signal Reception and transduction (peripheral proteins): bind to signal molecules (hormones) and change shape which initiates a response by the cell ​ Cell can RECEIVE and RESPOND to signals from the brain or other organs Bilayer ○​ Cell Recognition (glycoproteins): carbohydrates enable cells to “recognize”each other allows cells to identify harmful “intruders” like ​ Composed of phospholipids bacteria ○​ The head: Hydrophilic on both the inside and outside surfaces ○​ Reaction Catalysis (integral proteins): help to catalyze cellular reactions ​ The head’s POLAR phosphate part makes it polar. ​ Charged particles are attracted to this part of the membrane ○​ The tails: Hydrophobic and make up interior ​ Non-polar Important Terms ​ –Lipid part makes them non-polar ​ Semi-permeable membrane ○​ Prevents the passage of some substances but allows the passage of others based on differences in the size, charge, or lipid-solubility of the substances. ​ Passive Transport ○​ Movement of materials in and out of cell without usage of cellular energy ​ Active Transport ○​ Movement of materials in and out of cell which uses up cellular energy (ATP) Why Are Cells So Small? ​ Cells are microscopic in size. Not usually bigger than 1-100 micrometers (μm) ​ The average human body contains approximately 100 trillion cells. Why have multicellular organisms? Wouldn’t one big cell be better? Fluid-Mosaic Model of the Membrane ​ No organelle can be too far from the cell’s membrane. ​ Plasma membrane is very dynamic and complex system ​ The membrane is the door for letting things into and out of the cell. This includes food, ​ Lipid bilayers are fluid - individual phospholipids and proteins are free to drift around in waste and messages to other cells fluid motion ​ If they had to travel too far, too many things could go wrong ​ Known as fluid mosaic model of biological membranes (mosaic because it includes ○​ Responses would be too slow proteins, cholesterol, and other types of molecules beside phospholipids) ○​ Messages could get lost ○​ Wastes could poison the cell before they got out of Key Components of the Membrane In Addition ​ Volume increases faster than surface area ○​ Surface is the cell membrane. Phospholipids Main structural component where ○​ Bigger cells hold more stuff, but their cell membranes don’t increase in other components are embedded in size as quickly, with the increase in amount of stuff inside. ○​ Thus, you would get a “traffic jam” at the cell membrane, because a larger Cytoskeleton Structural support cell needs more nutrients and produces more wastes. Lesson 2.2 - The Cell Membrane and Transport Part 2 Cholesterol Affects fluidity (helps keep membrane together by increasing hydrophobic interactions) Proteins Various functions Carbohydrates Cell identification Effects on Fluidity of Bilayer ​ Temperature ○​ Higher temp = more fluid ​ Could stop acting as barrier if it becomes too fluid ○​ Lower temp = less fluid ​ Could eventually solidify to gel-like state ​ Unsaturated fatty acid tails ○​ Double bonds form kinks = less tightly packed tails (weakens hydrophobic interactions ​ “Tail” length ○​ Longer = greater hydrophobic interactions (decreases fluidity) Types of Transport ​ Passive ○​ Diffusion ○​ Osmosis ○​ Facilitated diffusion ​ Active ○​ Cell Membrane Pumps ​ Use proteins ○​ Vesicle-mediated transport ​ Endocytosis ​ Exocytosis Passive Diffusion ​ Solute – substances dissolved in fluid ot form solution ○​ Example: glucose, oxygen, and carbon dioxide ​ Higher oxygen gradient in freshly breathed air of alveoli than in the deoxygenated blood ​ Solvent – liquid in which solutes are dissolved of capillaries...so the oxygen travels along this gradient from the alveolus into the ​ All particles are randomly moving – even in solid bloodstream. ○​ Referred to as Brownian motion) ​ Similarly, carbon dioxide moves along its concentration gradient...traveling from the ​ Therefore, it is natural phenomenon that over time, particles tend to spread themselves blood into the alveolus air out evenly throughout any matter ​ Definition ○​ Tendency of particles to move from an area of high concentration and more random collisions, to an area of low concentration and fewer collisions. Osmosis ​ A special case of diffusion. ​ The movement of WATER molecules, across a selectively permeable membrane from an area of HIGH concentration to an area of LOW concentration until the water molecules on both sides of the membrane are equal, or until the pressures acting on either side of the membrane are equal to each other. ​ Equilibrium is established when distribution of particles is completely even ​ Movement is NOT from mechanical stress. Depends on movement of the molecules. ​ When particles move from areas of high to low concentration they are moving down (Kinetic Molecular Theory) concentration gradient ​ Cell membranes are permeable to water because water molecules are small enough to ​ Movement down gradient is passive transport sneak through ​ Driving force of movement of many molecules through cell membrane, like oxygen, ​ Very important to life, especially to single-celled organisms. carbon dioxide, alcohol, small lipids, is diffusion ​ If too much water enters the cell, the cell may burst ​ If too much water leaves the cell, the cell becomes FLACCID and may die Factors that Affect Rate of Diffusion Osmotic Concentrations ​ Osmotic concentration is determined by the concentration of solutes in a solution Molecule Size Larger molecules have more difficulty diffusing across HYPERTONIC When the fluid surrounding the cell is higher in dissolved ion concentration (or solute) than what is Molecule Polarity Polar molecules have a more difficult time than in a cell non-polar molecules HYPOTONIC When the fluid surrounding the cell is lower in Molecule/Ion Charge Charged molecules/ions cannot diffuse across dissolved ion concentration (or solute) than what is membrane in a cell Temperature Higher temperatures give molecules more energy to ISOTONIC When the surrounding fluid of the cell has the same move across faster amount of dissolved ions (or solute) as the inside does Pressure Higher pressure forces molecules across faster Isotonic Solution Diffusion in our Bodies - Gas Exchange in the Lungs ​ Equal water and solute concentration on both sides of the membrane ​ Involves: air sacs in lungs, called alveoli, and specialized blood vessels called capillaries ​ Same amount of water enters the cell as leaves the cell therefore ​ Alveoli and capillaries are extremely thin – short path for gases to travel from capillaries to alveoli ​ Many capillaries surround a single alveolus – increasing the surface area for diffusion to occur quickly  ​ There is no NET movement of material into or out of the cell Hypotonic Solution ​ Higher water concentration in the solution surrounding the cell than inside the cell membrane OR lower solute concentration in the solution than in the cell Facilitated Diffusion ​ Molecules enter the cell through channels that exist in special transport channel proteins or carrier proteins that span the membrane ​ Transport is still along the concentration gradient – so no cellular energy is required (no ATP) Active Transport ​ Requires energy, either from ATP(Adenosine TriPhosphate) or an electrochemical gradient to move molecules or ions AGAINST a concentration gradient (from low to high concentrations) ​ Requires carrier proteins ○​ E.g. sodium/potassium pump Hypertonic Solution ​ Higher solute concentration in the solution surrounding the cell than inside the cell Primary Active Transport membrane ​ Carrier proteins that pump ions across a membrane AGAINST a concentration gradient ​ Creates an electrochemical gradient Secondary Active Transport ​ Uses an electrochemical gradient as a source of energy to transport molecules or ions across a cell membrane  3 Types of Transport Proteins for Passive & Active Transport Membrane-Assisted Transport ​ Used to transport molecules that are too big to go through a channel or carrier protein (i.e. macromolecules) ​ Vesicles are formed to surround the molecule whether they are incoming or outgoing from the cel Channel Proteins Endocytosis ​ Phagocytosis ​ Tubular shape (hollow cylinder) ○​ An entire particle, solid or cell is engulfed ​ Exterior composed of amino acids with non-polar side chains (interact with non-polar fatty acid tails of phospholipids) ​ Some remain open all the time, some are gated (open and close in response to signals like hormones, electrical charge, pressure, or light) ​ Carry ions or small polar molecules ​ Pinocytosis ○​ The external fluid or solute is engulfed. Carrier Proteins ​ Have specific shapes to bind to specific molecules, transport them across membrane and release on other side ​ Change shape while transporting ​ Can carry larger molecules like glucose and amino acids ​ Receptor-mediated endocytosis ○​ Receptor proteins on the membrane binds to the molecule to be engulfed Exocytosis ​ A process where vesicle: ○​ Moves to the cell membrane, fuses with cell membrane, releases its contents to the outside of the cell ​ Used when large protein molecules from the Golgi Complex need to be moved out of the cell Exocytosis – examples: ​ Insulin made in the pancreatic cells...via the process of exocytosis, insulin molecules leave the pancreas and travel in the bloodstream ​ Digestive enzymes are made in the specialized cells of the lining of the intestines...via the process of exocytosis, these enzymes are able to leave the lining and enter the interior of the intestine... where digestion occurs  Lesson 3.1 - An Introduction to Metabolism Gibbs Free Energy (G) ​ In late 19th century Gibbs distinguished between energy and free energy ​ Gibbs free energy: energy that can do useful work ​ Can now describe the energy change in a chemical reaction in terms of a change in Gibbs free energy: two main types of reactions ○​ Exergonic ○​ Endergonic Metabolism Potential Energy Diagrams ​ Living organisms must continually capture, store and use energy to survive ​ Activation Energy (Ea) - The amount of energy needed to break the reactant’s bonds to ​ All work that occurs in organisms is at the molecular level through elaborate chemical get the reaction to “go” reactions ​ Transition State – a temporary condition in a reaction where bonds are breaking and ​ Metabolism = anabolism (building up) + catabolism (breaking down) forming Energy ​ Energy: the ability to do work ​ Exists in two states: ○​ Kinetic ​ Occurs as a result of motion (e.g. molecules and ions in a solution ○​ Potential ​ Energy stored within an object ​ Chemical Potential Energy ○​ Stored in the electrons and protons that make up atoms and molecules ○​ Chemical potential energy can be released or absorbed during a chemical reaction Adenosine Triphosphate (ATP) The Laws of Thermodynamics ​ Primary source of free energy in cells ​ ATP drives all cellular reactions by providing the energy that is needed. ​ First Law ○​ The total amount of energy in the universe is constant. Energy cannot be created or destroyed, but only converted from one form into another ○​ In living organisms energy is often transferred from one form to another ○​ E.g. Light energy captured by plants is converted to energy stored in bonds of glucose by photosynthesis. Cellular respiration releases this energy from glucose and stores it in the bonds of ATP ​ Second Law ○​ Every energy transfer or transformation increases the entropy of the universe ○​ Entropy is a measure of the randomness or disorder in energy or in a collection of objects. ○​ Both energy and entropy must be taken into account to determine if a reaction will occur spontaneously ​ If a cell requires free energy to drive a reaction an enzyme (ATPase) catalyses the Bond Energy hydrolysis of a phosphate group from the ATP molecule ​ A measure of the strength or stability of a covalent bond (kJ/mol) ​ Energy is released when bonds are formed ​ What types of energy are released? Coupled Reactions Why glucose? ​ Cells couple exergonic reactions (catabolic that release energy) with endergonic reactions ​ Many weak bonds with high free energy potential. (anabolic that need energy) ​ It is stable (won’t break down on its own) ​ ATP is an energy molecule that can used to provide the energy for an anabolic reaction ​ Easy to store as starch or glycogen. ​ ADP can be phosphorylated to ATP when it gains energy (in the form of a phosphate) ​ Water-soluble. from a catabolic reaction ​ Easy to transport in solution and can pass through membranes Cellular Respiration ​ C6H12O6 + 6O2 → 6CO2 + 6H2O + ENERGY ○​ As the bonds WITHIN the glucose molecule are broken down, energy is released ○​ Glucose stores energy in its bonds and cellular respiration is a way to acquire its bonds and cellular respiration is a way to acquire this energy ​ This is not one reaction, but a series of exergonic redox reactions. Exergonic Redox Reaction ​ C6H12O6 + 6O2 → 6CO2 + 6H2O + ENERGY Redox Reactions ○​ The bonds within glucose are broken through EXERGONIC ​ Many chemical reactions involve the transfer of one or more electrons from one reactant OXIDATION-REDUCTION reactions to another ○​ C6H12O6 oxidized to 6CO2 and 6O2 reduced to 6H2O ​ Losing electrons = called oxidation ​ Each carbon in C6H12O6 is converted to CO2 ​ Gaining electrons = called reduction. ​ Each hydrogen in C6H12O6 is converted to ½H2O ​ An electron transfer between two substances always involves an oxidation and a reduction and is called a redox reaction ​ Reactions can occur in a series in which the product of one redox reaction is the reactant Combustion of Glucose in the next reaction Lesson 3.2 - Cellular Respiration 1 - Overview Glycolysis Pyruvate Oxidation Each reaction requires ENZYMES ​ Kinases – attach phosphates ​ Dehydrogenases – remove H ​ Isomerases – change structure ​ Phosphatases – remove phosphates Aerobic vs Anaerobic Respiration ​ C6H12O6 + 6O2 → 6CO2 + 6H2O + ENERGY ​ In the above equation oxygen is the electron acceptor in the oxidation of glucose ​ Most organisms are obligate aerobes – they require oxygen and cannot survive without it ​ Obligate anaerobes (some species of bacteria) use other molecules as the final electron acceptor and must live in environments that has no oxygen ​ Facultative anaerobes can tolerate aerobic and anaerobic conditions Mitochondria How do Organisms Get Energy? ​ Photoautotrophs (e.g. plants) ○​ Through the sun ​ Chemoautotrophs (e.g. archaebacteria) ○​ Make organic compounds without sun’s energy ​ Heterotrophs (e.g. animal, fungi, most protists/bacteria) ○​ Through plants ○​ Glucose is the ultimate source of energy ○​ Glucose stores energy in its bonds and cellular respiration is a way to acquire this energy  Glycolysis - Overview ​ Takes Place in the Cytoplasm ​ Enzymes break down glucose (6 carbons) into two smaller molecules of pyruvate (3 carbons), releasing ATP ​ Does not require oxygen Energy Transfer Terminology ​ Substrate-level Phosphorylation: ○​ ATP forms directly in an enzyme-catalyzed reaction. ​ Oxidative Phosphorylation: ○​ ATP forms indirectly through a series of enzyme-catalyzed redox reactions involving oxygen as the final electron acceptor. ○​ Done mainly through compounds called energy carriers NAD+ and FAD+ ○​ These reactions harness energy, which is eventually transferred to ATP Energy Carriers ​ NAD+ (nicotinamide adenine dinucleotide) and FAD+ (flavin adenine dinucleotide) are low energy, oxidized coenzymes that act as electron acceptors. ​ When an electron(s) are added to these molecules, they become reduced to NADH and FADH2. ​ In this case, reducing a molecule gives it more energy. Aerobic Respiration: Overview ​ Occurs in Four Distinct Stages: ○​ Glycolysis: 10-step process in the cytoplasm ○​ Pyruvate Oxidation: 1-step process in the mitochondrial matrix. Glycolysis – Key parts of process ○​ Krebs Cycle: 8-step cyclical process in the mitochondrial matrix. ​ 2 ATPs are used in steps 1 & 3 to prime glucose for splitting ○​ Electron Transport Chain : Multi-step process in the inner mitochondrial ​ F 1,6-BP splits into DHAP and G3P membrane. ​ DHAP converts to G3P. ​ 2 NADH are formed in step 6. ​ 2 ATP are formed by substrate-level phosphorylation in both steps 7 and 10. ​ 2 pyruvates are produced in step 10. Glycolysis ​ Energy Yield & Products: ○​ 4 ATP produced – 2 ATP used = 2 net ATP ○​ 2 NADH and 2 pyruvates ​ Further processing in aerobic cellular respiration (if oxygen is available) Glycolysis – Energy Created ​ Creates 2 molecules of ATP (2 x 31 kJ/mol) ​ Yields 62 kJ of energy, from a possible 2870 kJ/glucose (only a 2.2% energy conversion) ​ Most energy is still trapped in pyruvate and the 2 NADH molecules, but some lost as heat ​ Earliest cells in Earth’s history thought to have used this method of energy metabolism since oxygen is not required and enough energy is produced to sustain life in unicellular organisms ​ Simple organisms today use glycolysis for energy ​ In multicellular organisms glycolysis takes place first in the cytoplasm, and then more processes in the mitochondria to cytoplasm, and then more processes in the mitochondria to yield more energy yield more energy Pyruvate Oxidation (if oxygen is present...) ​ The following occurs for each pyruvate: ○​ CO2 removed. ○​ NAD+ reduced to NADH and the 2-carbon compound becomes acetic acid ○​ Coenzyme A (CoA) attaches to acetic acid to form acetyl-CoA ○​ These reactions are catalyzed by a the pyruvate dehydrogenase complex (actually three enzymes) that convert pyruvate into acetyl-CoA by a process called pyruvate decarboxylation Energy Yield and Products ​ 2 NADH ​ 2 acetyl-CoA ​ 2 CO2 (released as waste) Acetyl-CoA ​ CoA comes from vitamin B5 ​ Proteins, lipids, and carbohydrates are catabolized to ‘acetyl-CoA’ ​ It can be used to make fat or ATP ​ [ATP] determines what pathway this molecule takes ​ If O2 is present, ‘acetyl Co’ moves to the Krebs Cycle (aerobic respiration) ​ If O2 is NOT present, ‘acetyl CoA’ becomes ‘lactate’ (anaerobic respiration / fermentation) Lesson 3.2 - Cellular Respiration 2 - Krebs, ETC, and Regulation Key Features Krebs cycle - overview ​ Step 1, acetyl-CoA combines with oxaloacetate to form citrate ​ NAD+ is reduced to NADH in steps 3, 4, and 8 ​ 8 step process, with each step catalyzed by a specific enzyme ​ FAD is reduced to FADH2 in step 6 ​ It is cycle because oxaloacetate is product of step 8 and reactant in step 1 ​ ATP is formed in step 5 by substrate-level phosphorylation. Phosphate group from ​ Two acetyl-CoA molecules enter, so Krebs Cycle must happen twice for every one succinyl-CoA is transferred to GDP, forming GTP, which then forms ATP molecule of glucose that begins glycolysis ​ Step 8, oxaloacetate is formed from malate ○​ Used as reactant in step 1 ​ CO2 is released in steps 3 and 4 Energy Yield & Products ​ 2 ATP ​ 6 NADH ​ 2 FADH2 ​ 4 CO2 (released as waste) ​ NADH and FADH2 carry electrons to electron transport chain for further production of ATP by oxidative phosphorylation Cellular Respiration so far has produced ​ Glycolysis ○​ 2 ATP (net) ○​ 2 NADH converted to 2 FADH2 ​ Pyruvate Oxidation ○​ 2 NADH ​ Krebs Cycle ○​ 2 ATP  ○​ 6 NADH ○​ Are abundant in positive charge, so create electrical gradient ○​ 2 FADH2 ​ Proton-motive force moves protons across ATP synthase ​ Protons are forced to pass back into matrix through special proton channels associated with ATP synthase Oxidative Phosphorylation ​ For every H+ that passes through, enough free energy is released to create 1 ATP from phosphorylation of ADP Final process ​ Process was called chemiosmosis because energy that drives A TP synthesis comes from ​ All carbon atoms of glucose have been used and converted to CO2 movement of protons through membrane ​ No oxygen used yet ​ Conditions must be aerobic because oxygen acts as final electron and H+ acceptor (water ​ Most of energy released in breakdown of glucose is being stored in NADH2 and FADH is formed as byproduct) molecules ​ Production of ATP in this way is referred to as oxidative phosphorylation ​ Oxidative phosphorylation is way for NADH2 and FADH molecules to release energy in coupled reaction to produce ATP ​ Two main process involved in oxidative phosphorylation ○​ Electron Transport Chain ○​ Chemiosmosis Oxidative Phosphorylation ETC Structure ​ Series of electron acceptors (proteins) are embedded in inner mitochondrial membrane ​ Proteins are arranged in order of increasing electronegativity ​ Weakest attractor of electrons (NADH dehydrogenase) is start of chain and strongest (cytochrome oxidase) is at end ​ Since mitochondrial membrane is highly folded, there are multiple copies of ETC across membrane ​ NADH and FADH2 transfer electrons to proteins in inner mitochondrial membrane ​ Weakest electron attractors are at start, and strongest are at end ​ Each component is REDUCED and then subsequently OXIDIZED ​ Oxygen (highly electronegative) oxidizes last ETC component ​ Energy releases, moves H+ atoms (i.e. protons) across mitochondrial membrane ATP Theoretical Yield ATP Actual Yield ​ 36 ATP is theoretical yield for many reasons ○​ Not all H+ atoms re-enter through ATP synthase (i.e. some leak) ○​ Some H+ atoms are used for other cellular processes ​ 30 ATP is actual yield from cellular respiration ​ Overall, cellular respiration is 32% efficient Controlling Aerobic Respiration ​ Regulated by feedback inhibition ​ Phosphofructokinase is allosteric enzyme that catalyzes third reaction in glycolysis and is inhibited by ATP and stimulated by ADP ​ If citrate (first product of Krebs cycle) accumulates, some will pass into cytoplasm and inhibit phosphofructokinase and slow down glycolysis Chemiosmosis – Electrochemical Gradient ​ As citrate is used up, concentration will decrease and rate of glycolysis will increase ​ High concentration of NADH indicates that ETC’s are full of electrons and ATP ​ Free energy released as electrons move through ETC is used to pump protons (H+) to production is high intermembrane space ​ NADH allosterically inhibits pyruvate dehydrogenase which reduces amount of ○​ 3 for every NADH and 2 for every FADH2 acetyl-CoA that is shuttled to Krebs cycle, reducing amount of NADH produced ​ H+ atoms outside mitochondria ○​ Are numerous, so create concentration gradient (i.e. chemical)  ○​ E.coli → some species will use O2 when it is available and when it is not may use other organic molecules like nitrates NO3-(aq) + 2e- + 2H+ → NO2-(aq) + H2O(l) ​ ​ electrons can be donated to ETC ○​ Methanogens use electron transport chains and generate hydrogen ion gradients that provide energy for phosphorylation – Use hydrogen that is synthesized by other organisms as an energy source and carbon dioxide as an electron acceptor ​ Some methanogens grow in swamps and marshes and are responsible for marsh gas (methane) ​ Some methanogens are in stomachs of cows and other ruminants (are major sources of methane released into the environment) Fermentation ​ Organisms have developed a way to oxidize NADH back into NADH back into NAD+ without requiring without req