The Working Cell Chapter 5 Overview • Energy • Metabolism • Enzymes • Metabolic Pathways Energy The capacity to do work In living organisms, chemical bonds are made & broken so that energy can be exchanged or transformed Kinetic Energy Energy of motion Work needed to accelerate an object from rest to its current velocity Includes light, sound, electricity, & heat energy Potential Energy The stored energy of position The work done by a certain force (e.g. gravity) on an object relative to its position Includes chemical & battery energy Kinetic and Potential Energy as a Pair Potential energy is converted into kinetic energy & vice versa Imagine a rubber band: When you stretch a rubber band, you give it potential energy When you release it, it has kinetic energy Thermodynamics The study of the effects of work, heat, & energy on a closed system Energy can be exchanged between physical systems as heat or work 1st Law of Thermodynamics “Energy can not be created or destroyed” A finite amount exists in various forms, which can be converted to other forms of energy e.g. from work to heat, from heat to light, from chemical to heat, etc. e.g. The chemical energy released from burning a substance is converted into light & heat energy In the conversion of energy from one form to another, some energy is lost as heat (i.e. not 100% efficient) Therefore, energy is unavailable to do work Heat is a disordered form of energy Release of heat makes universe more random & disorganized energy conversions ↓ order & ↑ entropy 2nd law of thermodynamics “Energy tends to flow from concentrated to less concentrated forms” Goes from being localized to being spread out (why hot things cool down when removed from heat, why air in a tire will escape from a small hole, etc.) Entropy The magnitude that concentrated energy has been dispersed after an energy change = how much energy is spread out or how widely it spreads out Unavailable energy (in a closed system, entropy can not decrease) Measure of disorder of a system (nature tends to go from order to disorder in closed systems) Time’s Arrow All energy spontaneously spreads out from a localized area to a more dispersed pattern (opposite does not occur spontaneously) In a closed system, everything will become more simple (i.e. will degenerate) over time Evolution’s basis is that simple organisms diversified into highly complex organisms So why don’t highly ordered living organisms violate the 2nd law of thermodynamics? Thermodynamics = closed system Earth = open system (earth exchanges heat, light, matter with its surroundings, including the sun) Organisms have low entropy and use energy to fight entropy If stop using energy → die Energy Flow Through The Biosphere Solar radiation is the ultimate source of energy in all food webs (captured by photoautotrophs) Glucose produced by each level is used up by level above At all levels, respiration occurs (releasing CO2, H2O, and energy from glucose) Energy is lost as heat between each level = 1-way flow where energy is used and dispersed 90% of energy lost between each level Metabolism and Energy Chemical reactions convert reactants to products by making or breaking bonds that hold atoms together Requires net inputs of energy to combine small molecules into larger ones that are more concentrated forms of energy Larger molecules can spontaneously degrade into smaller molecules, which ends with a release of energy Components of a Metabolic Reaction Reactant: Starting substance Intermediates: Formed before reaction ends Product: Substance remaining at end of reaction Some rxns are linear: Products formed directly from reactants Some rxns are cyclic: Final rxn regenerates the reactant molecule from the 1st step of the rxn; rxn then runs again Some rxns are branched: Intermediates or reactants are directed into 2 or more different series of rxns Most are reversible: Run spontaneously towards chemical equilibrium Rxn rate is about equal in both directions Allows cell to change activities via control of enzymes that enable steps of reversible metabolic pathways e.g. when cells need energy, glucose is split into 2 pyruvates via glycolysis (a 9-step pathway) When cells need glucose, they reverse the pathway & make glucose from pyruvate and other molecules If reversible pathway did not exist, cells would not be able to compensate for starvation episodes when glucose is low = cell death Endergonic Reactions Require energy Do not occur spontaneously (activation energy barrier is relatively high) Usually anabolic: A + B → AB (products have higher potential energy than reactants) Most reactions in cells are endergonic so cells have to store energy until it is needed e.g. biosynthesis of proteins Exergonic Reactions Generate energy (end with release of energy) Usually occur spontaneously (activation energy barrier is very low) Usually catabolic: AB → A + B (products have lower potential energy than reactants) e.g. hydrolysis, cellular respiration Coupled Reactions Reactions that require energy are paired with reactions that release energy e.g. sun releases energy that is needed to drive photosynthesis More energy is released from exergonic reactions than is used in endergonic reactions (extra energy is lost as heat) Coupled reactions often occur in different regions of the cell Living organisms require a mechanism for transporting energy released by exergonic reaction to site of endergonic reaction Energy-Carrier Molecules Are rechargeable Used only for short-term energy storage (unstable) Used only within a cell (not between cells) Most common energy-carrying molecule is ATP ATP Stores & releases chemical energy for all life processes Energy released during breakdown of nutrients (glucose, etc.) is captured as ATP ATP is coupling agent/energy carrier for most metabolic reactions When ATP gives up P, ADP forms Exergonic reaction = releases energy Energy can be used in endergonic reactions ATP reforms when ADP binds to inorganic phosphate or phosphate group from different molecule Endergonic reaction = requires energy Uses energy from other exergonic reactions ATP/ADP CYCLE ADENOSINE P P P ENDERGONIC EXERGONIC Energy via glucose P ADENOSINE P P + So essentially: ATP ADP + P + energy energy Some of energy at each step is lost as heat This heat warms living bodies Heat also provides activation energy for chemical reactions Electron Carriers Also transport energy within cells Play important role in metabolism During glucose breakdown & photosynthesis, some of energy is transferred to e-s E- carriers transport these high-energy e-s to other parts of cell Include NAD+ & FAD FAD NADH Electron Transfer Chains Membrane-bound groups of enzymes / molecules Accept & give up e-s in sequence E-s enter chain at higher energy level than when they leave it Lose energy at each descending step of chain Oxidation-Reduction (Redox Rxns) Stepwise electron transfers One molecule gives up e-s = oxidized One molecule gains e-s = reduced H+ atoms released simultaneously (are attracted to negative charge of e-s) Coenzymes pick up e-s & H+ from substrates and deliver to e- transfer chains If glucose was broken down all at once, all of the released energy would be lost as heat = Inefficient! Can’t be used to do work! Redox reactions allow efficient energy release Energy can be used to do cellular work e.g. ATP formation Metabolism All of the chemical reactions that occur within living cells Allow growth, reproduction, responsiveness, etc. Necessary for maintenance of life Metabolic pathways are series of linked reactions Photosynthesis Light energy converted into glucose 12H2O + 6CO2 6O2 + C6H12O6 + 6H2O Glycolysis Glucose converted into ATP Glucose → 2 pyruvate + 2 NADH + 2 ATP Cellular respiration (aerobic) Glucose converted into ATP in presence of O2 Glucose + 6O2 → 6CO2 + 6H2O + 36 ATP Fermentation Glucose converted into ATP in absence of O2 Glucose → 2 pyruvate + 2 NADH + 2 ATP Many interrelated chemical reactions & pathways = cells need mechanisms to control, coordinate, & connect these reactions 1. Enzymes act to ↑ rxn rate 2. Cells couple exergonic & endergonic rxns 3. Cells make energy-carrier molecules for short-term storage & transport of energy from exergonic rxns to endergonic rxns Reactions occur slowly Activation energy required for reactions to occur Rxn rate generally ↑ with ↑ heat Body temperature not enough to meet activation energy needs of most chemical rxns Cells use enzymes to ↓ activation energy needed = allows rxns to occur at body temperature Activation Energy = Minimum amount of energy required for a reaction to run Molecules have to collide with enough energy and in the correct orientation in order for molecules to react Overcomes repulsion between e- clouds of molecules so that bonds can be rearranged Cells can control when & how fast reactions occur by controlling energy inputs into reactions Catalysts Speed up rxn rates (lower the activation energy required to run a rxn) Are not used up Are not permanently altered Can be re-used Enzymes = biological catalysts Bind to molecules in ways that make it more likely that bonds will break & reactants will interact in the right way Usually proteins Structurally stable Substrate-specific (based on structure) Can be regulated Structure of an Enzyme Active site: Where substrate (reactant) enters enzyme Has right shape, size, & charge environment for substrate Allows for specificity Substrate The molecule upon which an enzyme acts Substrates have some structure that is complementary to an enzyme’s active site = allows for substrate recognition Substrate binds with active site Forms enzyme-substrate complex Both change shape due to binding Interactions between substrate & enzyme cause bonds to break and / or be formed Products produced do not fit in active site so are released from active site Enzyme returns to original shape & can be reused Induced-Fit Model Substrate is not exactly complementary to active site Enzyme molds substrate into specific shape that moves substrate to transition state = point at which colliding reactant molecules will always go on to form products Activation Energy Energy required to line up reactive chemical groups, destabilize electric charges, & break bonds Substrate reaches a transition state where bonds break & the reaction runs How Enzymes Work to Lower Activation Energy Enzyme binds weakly to substrate & energy is released Transition state is stabilized: Enzymes & substrate are kept together so reaction can run Other Helpful Enzymatic Things Help substrates get together Localize concentrations so that molecules can react Position substrates so reaction is favoured Bonds at active site put reactive groups close together so more directed collisions can occur Shut out water molecules Active sites have non-polar (hydrophobic) amino acids that repel water so that unwanted Hbonding doesn’t occur Controls over Enzymes Chemical reactions must be controlled Regulation of enzymes is 1° mechanism for controlling rxn rate Can be regulated via: • Adjusting speed of enzyme synthesis • Maintaining, increasing, or decreasing substance concentrations • Activating / inhibiting enzymes • Feedback inhibition • Allosteric regulation • Competitive inhibition Effects of Concentration Increased substrate concentration increases enzymatic activity Note: There is a point of saturation where all active sites are bound to substrate & reaction rate levels off Activation of Enzymes e.g. pepsin Can digest any protein Produced in non-active form Activated only in gastric fluid (pH 1 - 2) If activated pepsin leaked out of the stomach, would digest proteins in tissues Feedback Inhibition Maintains homeostasis in a cell by slowing metabolic pathways when products begin to accumulate Product produced as result of enzyme activity acts to reduce function of enzyme (if you already have enough of the product, why waste energy making more?) Inhibitors Decrease enzyme activity Irreversible: Changes enzyme chemically so can’t be used anymore Usually involves formation of covalent bonds Reversible: Non-covalent bonds that do not change enzyme Differential effects depending on what part of enzyme or enzyme-substrate complex is bound Allosteric Regulation A molecule binds at site other than active site = allosteric site Shape of enzyme is changed Active site is hidden (inhibited) or exposed (activated) Competitive Inhibition Inhibitor has similar structure as substrate so has affinity for active site of enzyme Competes with substrate for access to active site Increased concentration of substrate helps it outcompete inhibitor Many toxins / poisons act as competitive inhibitors Environmental Controls of Enzymes Enzymatic rates depend on environmental conditions Conditions that denature proteins will decrease or stop enzymatic activity Enzymes are affected by: – Temperature – pH – Salinity – Coenzymes Temperature As temperature , reaction rate (increased probability of collisions between molecules) Increase in substrate’s internal energy pushes reaction closer to activation energy At extreme temperatures, weak bonds are broken = alters enzyme shape (denaturation) Substrate can’t bind to active site, so reaction rate decreases / stops pH Most enzymes work best at pH 6 - 8 If not at optimal pH, rxn rate may decrease / stop Extreme pH values can cause denaturation of enzymes Coenzymes Organic compounds that may or may not have vitamin group Bind to enzymes Are necessary for enzyme function but are not part of the enzyme itself Are modified during the reaction but are regenerated elsewhere NADH Concept Check Enzymes catalyze the many reactions in a cell. There are hundreds of different enzymes in a cell—each with a unique three-dimensional shape. Why do cells have so many different enzymes? a. Each enzyme molecule can only be used once. b. The shape of an enzyme’s active site generally fits a specific substrate. c. The substrate molecules react with enzymes to create new enzymes. d. Enzymes are randomly produced. With thousands of different shapes, one is likely to work. Concept Check In order to start an exergonic reaction, a certain amount of energy must be absorbed by the reactants. This is called the energy of activation. Which of the following is the normal energy of activation? – A – B – C Concept Check Which of the following represents the energy of activation that is modified by an enzyme? – A – B – C