Chapter 8 - Metabolism

j / n K g CHAPTER 8 Introduction to Metabolism Campbell Reece Biology 7th Edition pp. 141-158 Concept 8.1 Organization of the Chemistry of Life into Metabolic Pathways Complexity of Metabolism The Laws of Energy Transformation Concept 8.2 d Exergonic and Endergonic Reactions in Metabolism An exergonic reaction Proceeds with a net release of free energy and is spontaneous The greater the decrease in free energy the greater the amount of work that can be done. E.g. overall cellular respiration reactions Concept 8.3 The Structure and Hydrolysis of ATP Energy is released from hydrolysis of ATP When the terminal phosphate bond is broken An exergonic reaction delta G is about -13 kcal/mol (cellular conditions) -7.3 kcal/mol standard conditions CHAPTER 8 Introduction to Metabolism Campbell Reece Biology 7th Edition pp. 141-158 Role of ATP Role of ATP hydrolysis Can be coupled to endergonic reactions by transferring the phosphate group to another molecule Drives endergonic reactions Overall coupled reactions are exergonic E.g. Glutamine synthesis The Regeneration of ATP Catabolic pathways Drive the regeneration of ATP from ADP and phosphate Concept 8.4 Rate of Metabolic Reactions The effect of enzymes on reaction rate reduce amount of absorbed heat required to reach transition state Substrate Specificity of Enzymes The catalytic cycle of an enzyme What affects the activity of enzyme-catalyzed reactions Effects of Temperature Effects of pH Cofactors Enzyme Inhibitors Competitive inhibitors Bind to the active site of an enzyme, competing with the substrate and blocks substrate binding Can be out-competed Concept 8.5 They change shape when regulatory molecules bind to specific sites, affecting function Feedback inhibition Localization of Enzymes Within the Cell Click to edit Master title style Click to edit Master text styles Second level Third level Fourth level Fifth level Click to edit Master text styles Second level Third level Fourth level Fifth level Enzyme 1 Enzyme 2 Enzyme 3 Reaction 1 Reaction 2 Reaction 3 Starting molecule Product Fig. 8.5 Figure 8.6 Reactants Products Energy Progress of the reaction Free energy (a) Exergonic reaction energy released D G Figure 8.6 Energy Products Reactants Progress of the reaction Free energy (b) Endergonic reaction energy required Figure 8.8 CH2 OH OH H N H H HC NH2 Adenine Ribose Phosphate groups O CH Figure 8.9 Adenosine triphosphate (ATP) H2O Energy Inorganic phosphate Adenosine diphosphate (ADP) P i hydrolysis of ATP releases a large amount of free energy EXERGONIC 2. ATP can be hydrolyzed ATP H2O ADP Pi free energy HPO42- very stable ATP - 2 unique features (c) Chemical work ATP phosphorylates key reactants Membrane protein Motor protein P i Protein moved (a) Mechanical work ATP phosphorylates motor proteins ATP (b) Transport work ATP phosphorylates transport proteins Solute P i transported Solute Glu Glu NH3 NH2 P i P i Reactants Glutamic acid and ammonia Product (glutamine) made ADP Figure 8.11 ATP synthesis from ADP P i requires energy ATP ADP P i Energy for cellular work (endergonic, energy- consuming processes) Energy from catabolism (exergonic, energy yielding processes) ATP hydrolysis to ADP P i yields energy Figure 8.12 Figure 8.13 H2O HO OH OH OH CH2OH CH2OH OH CH2OH Sucrase HO HO OH OH CH2OH CH2OH CH2OH Sucrose Glucose Fructose C12H22O11 C6H12O6 C6H12O6 OH Progress of the reaction Products Course of reaction without enzyme Reactants Course of reaction with enzyme EA without enzyme EA with enzyme is lower G Free energy Figure 8.15 Figure 8.16 Enzyme-substrate complex Substrate Substrates Products Enzyme Enzyme-substrate complex Figure 8.17 Enzymes are unaffected by the reaction (reusable ) How do they lower EA Act as a template for substrate orientation Stress substrates and stabilize the transition state Provides a favorable microenvironment Induced fit H-bonds, ionic bonds etc stabilize substrate Active site available Most metabolic reactions are reversible What influences reaction directions or velocity Each enzyme also has an optimal pH between pH 6 - 8 for most enzymes. Are exceptions Pepsin vs Trypsin (pH 2 and pH 8 respectively) Optimal temperature and pH favor the most active conformation of protein molecule Figure 8.19 A competitive inhibitor mimics the substrate, competing for the active site. (b) Competitive inhibition Competitive inhibitor A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme (a) Normal binding Bind to enzyme and inhibit its activity May be reversible or irreversible if irreversible - usually due to covalent bond between inhibitor and enzyme Figure 8.19 Noncompetitive inhibitor (c) Noncompetitive inhibition Binding is away from active site, alters conformation of enzyme active site no longer functions. Substrate Active site Enzyme (a) Normal binding Stabilized inactive form Allosteric activator stabilizes active from of all subunits Allosteric enyzme with four subunits Active site (one of four) Regulatory site (one of four) Active form Activator Stabilized active form Allosteric inhibitor stabilizes inactive form of all subunits Inhibitor Inactive form Non- functional active site Figure 8.20 Allosteric activators and inhibitors. Oscillation Figure 8.20 Inactive form Stabilized active form substrate Active site available Isoleucine used up by cell Feedback inhibition Isoleucine binds to allosteric site Initial substrate (threonine) Enzyme 1 (threonine deaminase) Intermediate A Intermediate B Intermediate C Intermediate D Enzyme 2 Enzyme 3 Enzyme 4 Enzyme 5 End product (isoleucine) Figure 8.21 1 m Mitochondria, sites of cellular respiration Figure 8.22 Increased localized concentration Organisms live at the expense of free energy During a spontaneous change Free energy decreases and the stability of a system increases Organisms live at the expense of free energy During a spontaneous change Free energy decreases and the stability of a system increases