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Energy and Metabolism 1 The Energy of Life • • • The living cell generates thousands of different reactions Metabolism • Is the totality of an organism’s chemical reactions • Arises from interactions between molecules An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics 2 Metabolic Pathways • • • • • Biochemical pathways are the organizational units of metabolism Metabolism is the total of all chemical reactions carried out by an organism A metabolic pathway has many steps that begin with a specific molecule and end with a product, each catalyzed by a specific enzyme Reactions that join small molecules together to form larger, more complex molecules are called anabolic. Reactions that break large molecules down into smaller subunits are called catabolic. Enzyme 1 A Enzyme 3 D C B Reaction 1 Starting molecule Enzyme 2 Reaction 2 Reaction 3 Product 3 Metabolic Pathway • A sequence of chemical reactions, where the product of one reaction serves as a substrate for the next, is called a metabolic pathway or biochemical pathway • Most metabolic pathways take place in specific regions of the cell. 4 Bioenergetics • • • Bioenergetics is the study of how organisms manage their energy resources via metabolic pathways Catabolic pathways release energy by breaking down complex molecules into simpler compounds Anabolic pathways consume energy to build complex molecules from simpler ones 5 Energy • Energy is the capacity to do work or ability to cause change. Any change in the universe requires energy. Energy comes in 2 forms: • Potential energy is stored energy. No change is currently taking place • Kinetic energy is currently causing change. This always involves some type of motion. 6 Forms of Energy • • • Kinetic energy is the energy associated with motion Potential energy • Is stored in the location of matter • Includes chemical energy stored in molecular structure Energy can be converted from one form to another On the platform, a diver has more potential energy. Climbing up converts kinetic energy of muscle movement Diving converts potential energy to kinetic energy. In the water, a diver has less potential energy. to potential energy. 7 Laws of Energy Transformation • • Thermodynamics is the study of energy changes. Two fundamental laws govern all energy changes in the universe. These 2 laws are simply called the first and second laws of thermodynamics: 8 The First Law of Thermodynamics • According to the first law of thermodynamics • Energy cannot be created or destroyed • Energy can be transferred and transformed Chemical energy For example, the chemical (potential) energy in food will be converted to the kinetic energy of the cheetah’s movement 9 Second Law of Thermodynamics • The disorder (entropy) in the universe is continuously increasing. • Energy transformations proceed spontaneously to convert matter from a more ordered, less stable form, to a less ordered, more stable form • Spontaneous changes that do not require outside energy increase the entropy, or disorder, of the universe • For a process to occur without energy input, it must increase the entropy of the universe 10 Second Law of Thermodynamics • • • • • During each conversion, some of the energy dissipates into the environment as heat. During every energy transfer or transformation, some energy is unusable, often lost as heat Heat is defined as the measure of the random motion of molecules Living cells unavoidably convert organized forms of energy to heat According to the second law of thermodynamics, every energy transfer or transformation increases the entropy (disorder) of the universe Heat co2 + H2O For example, disorder is added to the cheetah’ssurroundings in the form of heat and the small molecules that are the by-products of metabolism. 11 Biological Order and Disorder • Cells create ordered structures from less ordered materials • Organisms also replace ordered forms of matter and energy with less ordered forms • The evolution of more complex organisms does not violate the second law of thermodynamics • Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases 12 Biological Order and Disorder • Living systems • Increase the entropy of the universe • Use energy to maintain order • A living system’s free energy is energy that can do work under cellular conditions • Organisms live at the expense of free energy 50µm 13 Free Energy • Free energy (G) is a measure of the amount of energy available to do useful work. It depends on: • The total amount of energy present; this is called enthalpy (H) • The amount of energy being used for non-useful work (random molecular motion); this is called entropy (S). 14 Free Energy • In general: ΔG = ΔH - T ΔS • Where T represents the temperature in degrees Kelvin and Δ represent “the change in”. • This means the amount of energy available for useful work (G) equals the total energy present (H) minus the energy that is being wasted on random molecular motion (S). 15 Free Energy • • • Free energy is the portion of a system’s energy that is able to perform work when temperature and pressure is uniform throughout the system, as in a living cell Free energy also refers to the amount of energy actually available to break and subsequently form other chemical bonds Gibbs’ free energy (G) – in a cell, the amount of energy contained in a molecule’s chemical bonds (T&P constant) • Change in free energy - ΔG • Endergonic - any reaction that requires an input of energy • Exergonic - any reaction that releases free energy 16 Exergonic reactions • • Reactants have more free energy than the products Involve a net release of energy and/or an increase in entropy Occur spontaneously (without a net input of energy) Reactants Free energy • Amount of energy released (∆G <0) Energy Products Progress of the reaction (a) Exergonic reaction: energy released 17 Endergonic Reactions • Reactants have less free energy than the products • Involve a net input of energy and/or a decrease in entropy • Do not occur spontaneously Free energy Products Energy Amount of energy released (∆G>0) Reactants Progress of the reaction (b) Endergonic reaction: energy required 18 Energy released Energy supplied Product Energy must be supplied. Reactant Reactant Energy is released. Product Endergonic Exergonic 19 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Equilibrium and Metabolism • Reactions in a closed system eventually reach equilibrium and then do no work • Cells are not in equilibrium; they are open systems experiencing a constant flow of materials • A catabolic pathway in a cell releases free energy in a series of reactions • Closed and open hydroelectric systems can serve as analogies 20 Equilibrium and Metabolism • Reactions in a closed system eventually reach equilibrium ∆G < 0 ∆G = 0 (a) A closed hydroelectric system. Water flowing downhill turns a turbine that drives a generator providing electricity to a light bulb, but only until the system reaches equilibrium. • Cells in our body experience a constant flow of materials in and out, preventing metabolic pathways from reaching equilibrium (b) An open hydroelectric system. Flowing water keeps driving the generator because intake and outflow of water keep the system from reaching equlibrium. ∆G < 0 21 An Analogy For Cellular Respiration – Glucose Catabolism ∆G < 0 ∆G < 0 ∆G < 0 (c) A multistep open hydroelectric system. Cellular respiration is analogous to this system: Glucoce is brocken down in a series of exergonic reactions that power the work of the cell. The product of each reaction becomes the reactant for the next, so no reaction reaches equilibrium. 22 Energy Coupling • • • Living organisms have the ability to couple exergonic and endergonic reactions: Energy released by exergonic reactions is captured and used to make ATP from ADP and Pi ATP can be broken back down to ADP and Pi, releasing energy to power the cell’s endergonic reactions. 23 The Structure and Hydrolysis of ATP • ATP (adenosine triphosphate) • Is the cell’s energy shuttle • Provides energy for cellular functions Adenine N O O -O O - - O O Phosphate groups O C C N HC O O O NH2 N CH2 - O H N H H H OH CH C Ribose OH 24 The Structure and Hydrolysis of ATP • Energy is released from ATP when the terminal phosphate bond is broken P P P Adenosine triphosphate (ATP) H2O P i + Inorganic phosphate P P Energy Adenosine diphosphate (ADP) 25 Cellular Work • A cell does three main kinds of work • Mechanical • Transport • Chemical • Energy coupling is a key feature in the way cells manage their energy resources to do this work • ATP powers cellular work by coupling exergonic reactions to endergonic reactions 26 Energy Coupling - ATP / ADP Cycle • • • Releasing the third phosphate from ATP to make ADP generates energy (exergonic): Linking the phosphates together requires energy - so making ATP from ADP and a third phosphate requires energy (endergonic), Catabolic pathways drive the regeneration of ATP from ADP and phosphate ATP hydrolysis to ADP + P i yields energy ATP synthesis from ADP + P i requires energy ATP Energy from catabolism (exergonic, energy yielding processes) Energy for cellular work (endergonic, energyconsuming processes) ADP + P i 27 How ATP Performs Work • ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant • The recipient molecule is now phosphorylated • The three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP 28 How ATP Performs Work • ATP drives endergonic reactions by phosphorylation, transferring a phosphate to other molecules - hydrolysis of ATP P i P Motor protein Protein moved (a) Mechanical work: ATP phosphorylates motor proteins Membrane protein ADP + ATP P P Solute P i i Solute transported (b) Transport work: ATP phosphorylates transport proteins P Glu + NH3 Reactants: Glutamic acid and ammonia NH2 Glu + P i Product (glutamine) made (c) Chemical work: ATP phosphorylates key reactants 29 Activation Energy • All reactions, both endergonic and exergonic, require an input of energy to get started. This energy is called activation energy The activation energy, EA • • • Is the initial amount of energy needed to start a chemical reaction Activation energy is needed to bring the reactants close together and weaken existing bonds to initiate a chemical reaction. Is often supplied in the form of heat from the surroundings in a system. A B C D Transition state Free energy • A B C D EA Reactants A B ∆G < O C D Products Progress of the reaction Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 30 Reaction Rates • In most cases, molecules do not have enough kinetic energy to reach the transition state when they collide. • Therefore, most collisions are non-productive, and the reaction proceeds very slowly if at all. • What can be done to speed up these reactions? 31 Increasing Reaction Rates Activation Energy and Catalysis Energy supplied • Add Energy (Heat) - molecules move faster so they collide more frequently and with greater force. Add a catalyst – a catalyst reduces the energy needed to reach the activation state, without being changed itself. Proteins that function as catalysts are called enzymes. Energy released • Activation energy Activation energy Reactant Reactant Product Uncatalyzed Product Catalyzed 32 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Enzymes Lower the EA Barrier An enzyme catalyzes reactions by lowering the EA barrier Course of reaction without enzyme Free energy • EA without enzyme EA with enzyme is lower Reactants ∆G is unaffected by enzyme Course of reaction with enzyme Products Progress of the reaction 33 Enzymes Are Biological Catalysts • Enzymes are proteins that carry out most catalysis in living organisms. • Unlike heat, enzymes are highly specific. Each enzyme typically speeds up only one or a few chemical reactions. • Unique three-dimensional shape enables an enzyme to stabilize a temporary association between substrates. • Because the enzyme itself is not changed or consumed in the reaction, only a small amount is needed, and can then be reused. • Therefore, by controlling which enzymes are made, a cell can control which reactions take place in the cell. 34 Substrate Specificity of Enzymes • • • • • • • Almost all enzymes are globular proteins with one or more active sites on their surface. The substrate is the reactant an enzyme acts on Reactants bind to the active site to form an enzyme-substrate complex. The 3-D shape of the active site and the substrates must match, like a lock and key Binding of the substrates causes the enzyme to adjust its shape slightly, leading to a better induced fit. Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the chemical reaction When this happens, the substrates are brought close together and existing bonds are stressed. This reduces the amount of energy needed to reach the transition state. Substate Active site Enzyme Enzyme- substrate complex 35 The Catalytic Cycle Of An Enzyme 1 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). Substrates Enzyme-substrate complex 6 Active site Is available for two new substrate Mole. Enzyme 5 Products are Released. Figure 8.17 Products 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. 3 Active site (and R groups of its amino acids) can lower EA and speed up a reaction by • acting as a template for substrate orientation, • stressing the substrate bonds and stabilizing the transition state, • providing a favorable microenvironment, • participating directly in the catalytic reaction. 4 Substrates are Converted into Products. 36 The Catalytic Cycle Of An Enzyme 1 The substrate, sucrose, consists of glucose and fructose bonded together. Glucose Fructose 2 The substrate binds to the enzyme, forming an enzyme-substrate complex. Bond H2O Active site Enzyme 4 Products are released, and the enzyme is free to bind other substrates. 3 The binding of the substrate and enzyme places stress on the glucose-fructose bond, and the bond breaks. 37 Factors Affecting Enzyme Activity • • • Temperature - rate of an enzyme-catalyzed reaction increases with temperature, but only up to an optimum temperature. pH - ionic interactions also hold enzymes together. Inhibitors and Activators 38 Effects of Temperature and pH Each enzyme has an optimal temperature in which it can function Optimal temperature for typical human enzyme Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria Rate of reaction • 0 20 40 Temperature (Cº) (a) Optimal temperature for two enzymes 80 100 39 Effects of Temperature and pH Each enzyme has an optimal pH in which it can function Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) Rate of reaction • 3 4 0 2 1 (b) Optimal pH for two enzymes 5 6 7 8 9 Figure 8.18 40 Factors Affecting Enzyme Activity • Inhibitor - substance that binds to an enzyme and decreases its activity – feedback • Competitive inhibitors - compete with the substrate for the same active site • Noncompetitive inhibitors - bind to the enzyme in a location other than the active site • Allosteric sites - specific binding sites acting as on/off switches 41 Enzyme Inhibitors • Competitive inhibitors bind to the active site of an enzyme, competing with the substrate A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme (a) Normal binding A competitive inhibitor mimics the substrate, competing for the active site. Competitive inhibitor (b) Competitive inhibition 42 Enzyme Inhibitors • Noncompetitive inhibitors bind to another part of an enzyme, changing the function A noncompetitive inhibitor binds to the enzyme away from the active site, altering the conformation of the enzyme so that its active site no longer functions. Noncompetitive inhibitor (c) Noncompetitive inhibition 43 Regulation Of Enzyme Activity Helps Control Metabolism Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated • To regulate metabolic pathways, the cell switches on or off the genes that encode specific enzymes • Allosteric regulation is the term used to describe any case in which a protein’s function at one site is affected by binding of a regulatory molecule at another site • Enzymes change shape when regulatory molecules bind to specific sites, affecting function • 44 Allosteric Activation and Inhibition • • • • Most allosterically regulated enzymes are made from polypeptide subunits Each enzyme has active and inactive forms The binding of an activator stabilizes the active form of the enzyme The binding of an inhibitor stabilizes the inactive form of the enzyme 45 Allosteric Regulation of Enzymes • Allosteric regulation may either inhibit or stimulate an enzyme’s activity Allosteric enyzme with four subunits Active site (one of four) Regulatory site (one of four) Allosteric activater stabilizes active from Activator Active form Stabilized active form Allosteric activater stabilizes inactive form Oscillation Nonfunctional active site Inactive form Inhibitor Stabilized inactive form (a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again. 46 Cooperativity • Is a form of allosteric regulation that can amplify enzyme activity Binding of one substrate molecule to active site of one subunit locks all subunits in active conformation. Substrate Inactive form Stabilized active form (b) Cooperativity: another type of allosteric activation. Note that the inactive form shown on the left oscillates back and forth with the active form when the active form is not stabilized by substrate. 47 Factors Affecting Enzyme Activity • Activators - substances that bind to allosteric sites and keep the enzymes in their active configurations - increases enzyme activity • Cofactors - chemical components that facilitate enzyme activity • Coenzymes - organic molecules that function as cofactors 48 Regulation of Biochemical Pathways • • • Biochemical pathways must be coordinated and regulated to operate efficiently. Advantageous for cell to temporarily shut down biochemical pathways when their products are not needed Feedback Inhibition 49 Feedback Inhibition • • In feedback inhibition the end product of a metabolic pathway shuts down the pathway When the cell produces increasing quantities of a particular product, it automatically inhibits its ability to produce more Active site available Initial substrate (threonine) Threonine in active site Enzyme 1 (threonine deaminase) Isoleucine used up by cell Intermediate A Feedback inhibition Active site of enzyme 1 no longer binds threonine; pathway is switched off Enzyme 2 Intermediate B Enzyme 3 Intermediate C Isoleucine binds to allosteric site Enzyme 4 Intermediate D Enzyme 5 End product (isoleucine) 50