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Transcript
Ch 8 Cellular Metabolism How cells utilize energy LE 8-2 On the platform, the diver has more potential energy. Diving converts potential energy to kinetic energy. Climbing up converts kinetic energy of muscle movement to potential energy. In the water, the diver has less potential energy. LE 8-3 Heat Chemical energy First law of thermodynamics CO2 H2O Second law of thermodynamics The First Law of Thermodynamics – Energy cannot be created or destroyed – Energy can be transferred and transformed Principle of conservation of energy The Second Law of Thermodynamics • Every energy transfer or transformation increases the entropy (disorder) of the universe • Because some energy is lost as heat (unusable) • Metabolism – an organism’s (or cell’s) total chemical reactions Name a common cellular reaction. Two kinds of reactions: Catabolism (catabolic rxn) Breakdown of a larger molecule into smaller lower energy products Releases of energy Exergonic rxn Anabolism (anabolic rxn) Synthesis of larger high energy molecules from lower energy reactants Requires input of energy Endergonic reactions LE 8-12 ATP Energy for cellular work (endergonic, energyconsuming processes) Energy from catabolism (exergonic, energyyielding processes) ADP + P i Cellular energy used for: transport (across membranes) mechanical work (motility, contraction) enzymatic activity (catalysis of reactions) Examples Catabolic rxn C6H12O6 + 6O2 ----> 6CO2 + 6H2O + ATP glucose Exergonic Anabolic rxn Light 6CO2 + 6H2O ----> C6H12O6 + 6O2 glucose Endergonic Biological rxns -Catalyzed by enzymes -Often arranged in multiple steps called pathways LE 8-UN141 Enzymatic Pathway Enzyme 1 A B Reaction 1 Starting molecule Enzyme 2 Enzyme 3 D C Reaction 2 Reaction 3 Product Enzymes Biological catalysts Increase rate of reactions by lowering activation energy (EA) Spontaneous reactions can take a long time! Need enzymes to speed reactions for cell survival Activation Energy (EA) • Needed to destabilize bonds of reactants LE 8-14 A B C D Free energy Transition state A B C D Could raise temp. to break bonds EA Reactants A B DG < O C D Products Progress of the reaction Why don’t cells rely on increases in temperature to break bonds? Denaturation of proteins and damage to the cell. LE 8-15 Free energy Course of reaction without enzyme EA without enzyme EA with enzyme is lower Reactants Course of reaction with enzyme DG is unaffected by enzyme Products Progress of the reaction LE 8-13 Example: Sucrose C12H22O11 Glucose C6H12O6 Fructose C6H12O6 Structure & Function of Enzyme DRAW • Enzymes bind substrate molecules (the reactant) • Substrates bind to active site on enzyme • Binding induces conformational change in enzyme--better ”fit” for substrate • Active sites are highly specific and discriminatory i.e. sucrase does not accept lactose LE 8-16 Substrate Active site Enzyme Enzyme-substrate complex How does enzyme lower activation energy of reaction? – Orients substrates for optimal interaction –Strains substrate bonds –Provides a favorable microenvironment -Covalently bonds to the substrate LE 8-17 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. Substrates Enzyme-substrate complex Active site is available for two new substrate molecules. Enzyme Products are released. Substrates are converted into products. Products 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 substrates and stabilizing the transition state, • providing a favorable microenvironment, • participating directly in the catalytic reaction. How do we know when a reaction is exergonic or endergonic? Measure the system’s ability to perform work (usable energy) at uniform temperature and pressure. Change in Gibbs free energy (G) DG= DH-TDS Where DH= change in total energy of the system, or enthalpy T=absolute temperature in Kelvin (oC+273) DS =change in entropy (a measure of disorder) Another way to think about the state of energy in a cell is before and after a particular reaction occurs DG = G final state - G initial state (products) (reactants) If the reaction gives final products that have less energy than the initial reactants, is DG negative or positive? The reverse? When DG < 0, the reaction is exergonic and spontaneous. When DG > 0, the reaction is endergonic and not spontaneous. LE 8-6a Reactants Free energy Amount of energy released (DG < 0) Products Energy Progress of the reaction Exergonic reaction: energy released Catabolic rxn C6H12O6 + 6O2 ----> 6CO2 + 6H2O + ATP glucose LE 8-6b Free energy Products Energy Amount of energy required (DG > 0) Reactants Progress of the reaction Endergonic reaction: energy required Anabolic rxn Light 6CO2 + 6H2O ----> C6H12O6 + 6O2 glucose Relationship among Free Energy, Instability, and Equilibrium • Free energy: – a measure of a system’s instability, its tendency to change to a more stable state • During a spontaneous change – free energy decreases and the stability of a system increases • Equilibrium is a state of maximum stability (DG=0) • If the metabolism of a cell is at equilibrium, what has occurred? RIP LE 8-12 ATP Energy for cellular work (endergonic, energyconsuming processes) Energy from catabolism (exergonic, energyyielding processes) ADP + P i Cellular energy used for: transport (across membranes) mechanical work (motility, contraction) enzymatic activity (catalysis of reactions) ATP structure • ATP – adenosine triphosphate • cellular energy carrier LE 8-8 ATP structure Adenosine triphosphate Cellular energy currency g b Adenine (base) a Phosphate groups Ribose (sugar) LE 8-9 P P P Adenosine triphosphate (ATP) H2O Pi + Inorganic phosphate P P Adenosine diphosphate (ADP) + Energy • Terminal phosphate bond (ATP--> ADP + Pi) – Hydrolysis of “high energy” phosphate bond • Energy is released (exergonic) • ADP lower energy than ATP • Why? • Is ADP more stable than ATP? Explain. LE 8-8 Adenine g b a Phosphate groups Ribose • Energy from ATP hydrolysis – drives endergonic reactions • Overall, coupled reactions are exergonic LE 8-10 Endergonic reaction: DG is positive, reaction is not spontaneous NH2 Glu + NH3 Ammonia Glutamic acid DG = +3.4 kcal/mol Glu Glutamine Exergonic reaction: DG is negative, reaction is spontaneous ATP + H2O ADP Coupled reactions: Overall DG is negative; together, reactions are spontaneous + Pi DG = –7.3 kcal/mol DG = –3.9 kcal/mol How ATP Performs Work • Inorganic phosphate from ATP hydrolysis – Transferred to target molecule • Called phosphorylation • Creates highly reactive, unstable target molecule • More prone to do “work” or change (conformation) – Mechanical, transport, enzymatic LE 8-11 Pi P Motor protein Protein moved Mechanical work: ATP phosphorylates motor proteins Membrane protein ADP + Pi ATP Pi P Solute transported Solute Transport work: ATP phosphorylates transport proteins P NH2 Glu + NH3 + Pi Glu Reactants: Glutamic acid and ammonia Product (glutamine) made Chemical work: ATP phosphorylates key reactants Regeneration of ATP • ADP + P i--> ATP – Energy for ADP phosphorylation from catabolic reactions LE 8-12 ATP Energy for cellular work (endergonic, energyconsuming processes) Energy from catabolism (exergonic, energyyielding processes) ADP + P i Environmental Conditions Affect Enzyme Function ? Temperature: cold-->decreased chance of bumping into substrate hot--> good chance of substrate interaction but chance of denaturation at some point pH->change in charge (H+ or OH-) can denature proteins and substrate Examples of pH sensitive enzymes? LE 8-18 Optimal temperature for typical human enzyme What is your normal body temp.? 0 Optimal temperature for enzyme of thermophilic (heat-tolerant bacteria) 40 60 Temperature (°C) 20 80 100 Optimal temperature for two enzymes Optimal pH for pepsin (stomach enzyme) 0 1 2 3 4 Optimal pH for trypsin (intestinal enzyme) 5 pH Optimal pH for two enzymes 6 7 8 9 10 Cofactors • Non-protein enzyme helpers (like metals (Fe)) •Coenzymes •organic cofactors •Vitamins •e.g. Vitamin K: required for blood clotting & Required in certain carboxylation reactions Regulation of Enzymes Enzyme Inhibitors • Competitive inhibitor – binds to active site of enzyme – blocks substrate binding by competition •Noncompetitive inhibitor – binds to another part of enzyme – causes enzyme to change shape – prevents active site from binding substrate –Allosteric effect DRAW LE 8-19 A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme Normal binding A competitive inhibitor mimics the substrate, competing for the active site. Competitive inhibitor Competitive inhibition 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 Noncompetitive inhibition Allosteric Regulation of Enzymes • Where protein function at one site is affected by binding of a regulatory molecule at another site • May inhibit or stimulate enzyme activity Allosteric Activation and Inhibition • Most allosterically regulated enzymes are made from polypeptide subunits • active and inactive forms • binding of activator stabilizes active form of enzyme • binding of inhibitor stabilizes inactive form of enzyme LE 8-20a Allosteric enzyme with four subunits Regulatory site (one of four) Active site (one of four) Activator Active form Oscillation Nonfunctional active site Allosteric activator stabilizes active form. Inactive form Stabilized active form Allosteric inhibitor stabilizes inactive form. Inhibitor Allosteric activators and inhibitors Stabilized inactive form • Cooperativity – form of allosteric regulation that can amplify enzyme activity • binding of substrate to one active site stabilizes favorable conformational changes at all other subunits LE 8-20b Binding of one substrate molecule to active site of one subunit locks all subunits in active conformation. Substrate Inactive form Stabilized active form Cooperativity another type of allosteric activation Feedback Inhibition • End product of a metabolic pathway shuts down the pathway • Prevents over-production of unneeded molecules LE 8-21 Initial substrate (threonine) Active site available Isoleucine used up by cell Threonine in active site Enzyme 1 (threonine deaminase) Intermediate A Feedback inhibition Enzyme 2 Active site of enzyme 1 can’t bind Intermediate B theonine pathway off Enzyme 3 Isoleucine binds to allosteric site Intermediate C Enzyme 4 Intermediate D Enzyme 5 End product (isoleucine) Metabolic regulation influenced by cellular localization • Cellular structures organize and concentrate enzymes in pathways – Membranes, organelles (mitochondria, chloroplast) LE 8-22 Mitochondria, sites of cellular respiration 1 µm LE 8-22 It’s nice to get so much attention!