An Introduction to Metabolism Chapter 6 An Introduction to Metabolism p. 116-134

Concept 6.1: An organism’s metabolism transforms matter and energy Metabolism is… Metabolism is an emergent property of life that arises from interactions between molecules within the cell A metabolic pathway begins with a specific molecule and ends with a product, and each step is catalyzed by a specific enzyme © 2014 Pearson Education, Inc. 2

Enzyme 1 Enzyme 2 Enzyme 3 Starting molecule A B C D Product Figure 6.UN01 Enzyme 1 Enzyme 2 Enzyme 3 Starting molecule A B C D Product Reaction 1 Reaction 2 Reaction 3 Figure 6.UN01 In-text figure, metabolic pathway schematic, p. 116 3

Catabolism Anabolism

Forms of Energy Energy Kinetic energy Thermal energy Heat Potential energy Chemical energy 5

A diver has more potential energy on the platform. Figure 6.2 Diving converts potential energy to kinetic energy. A diver has more potential energy on the platform. Figure 6.2 Transformations between potential and kinetic energy Climbing up converts the kinetic energy of muscle movement to potential energy. A diver has less potential energy in the water. 6

The Laws of Energy Transformation Thermodynamics= Isolated System Open System 7

According to the first law of thermodynamics, the energy of the universe is constant Energy can be transferred and transformed, but it cannot be created or destroyed Figure 6.3a The two laws of thermodynamics (part 1: conservation of energy) Chemical energy (a) First law of thermodynamics 8

According to the second law of thermodynamics: Every energy transfer or transformation increases the entropy of the universe Heat Figure 6.3b The two laws of thermodynamics (part 2: entropy) (b) Second law of thermodynamics 9

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 How does energy flow into an ecosystem? How does it flow out? © 2014 Pearson Education, Inc. 10

Concept 6.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously A living system’s free energy (G) is energy that can do work when temperature and pressure are uniform What is ΔG? © 2014 Pearson Education, Inc. 11

More free energy (higher G) Less stable Greater work capacity Figure 6.5 More free energy (higher G) Less stable Greater work capacity In a spontaneous change The free energy of the system decreases (G  0) The system becomes more stable The released free energy can be harnessed to do work Figure 6.5 The relationship of free energy to stability, work capacity, and spontaneous change Less free energy (lower G) More stable Less work capacity (a) Gravitational motion (b) Diffusion (c) Chemical reaction 12

Exergonic and Endergonic Reactions in Metabolism Exergonic Reactions Endergonic Reactions © 2014 Pearson Education, Inc. 13

Amount of energy released (G  0) Amount of energy required (G  0) Figure 6.6 (a) Exergonic reaction: energy released, spontaneous Reactants Amount of energy released (G  0) Energy Free energy Products Progress of the reaction (b) Endergonic reaction: energy required, nonspontaneous Products Figure 6.6 Free energy changes (ΔG) in exergonic and endergonic reactions Amount of energy required (G  0) Energy Free energy Reactants Progress of the reaction 14

(a) An isolated hydroelectric system Figure 6.7 G  0 G  0 (a) An isolated hydroelectric system (b) An open hydroelectric system G  0 Figure 6.7 Equilibrium and work in isolated and open systems G  0 G  0 G  0 (c) A multistep open hydroelectric system 15

Concept 6.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions A cell does three main kinds of work Chemical Transport Mechanical Cells utilize energy coupling © 2014 Pearson Education, Inc. 16

The Structure and Hydrolysis of ATP Adenine Phosphate groups Ribose (a) The structure of ATP Adenosine triphosphate (ATP) Figure 6.8 The structure and hydrolysis of adenosine triphosphate (ATP) Energy Inorganic phosphate Adenosine diphosphate (ADP) Figure 6.8 (b) The hydrolysis of ATP 17

Figure 6.9: How ATP drives chemical work! GGlu  3.4 kcal/mol Glutamic acid Ammonia Glutamine (a) Glutamic acid conversion to glutamine Glutamic acid Phosphorylated intermediate Glutamine (b) Conversion reaction coupled with ATP hydrolysis GGlu  3.4 kcal/mol Figure 6.9 How ATP drives chemical work: energy coupling using ATP hydrolysis GGlu  3.4 kcal/mol GATP  −7.3 kcal/mol GATP  −7.3 kcal/mol  (c) Free-energy change for coupled reaction G  −3.9 kcal/mol Net 18

Figure 6.10 How ATP drives transport and mechanical work Transport protein Solute Solute transported (a) Transport work: ATP phosphorylates transport proteins. Vesicle Cytoskeletal track Figure 6.10 How ATP drives transport and mechanical work Motor protein Protein and vesicle moved (b) Mechanical work: ATP binds noncovalently to motor proteins and then is hydrolyzed. 19

The Regeneration of ATP Energy from catabolism (exergonic, energy- releasing processes) Energy for cellular work (endergonic, energy-consuming processes) Figure 6.11 The ATP cycle Figure 6.11 20

Concept 6.4: Enzymes speed up metabolic reactions by lowering energy barriers Sucrase Sucrose (C12H22O11) Glucose (C6H12O6) Fructose (C6H12O6) Figure 6.UN02 In-text figure, hydrolysis of sucrose, p. 125 Figure 6.UN02 21

Figure 6.12: An energy profile of an exergonic reaction B C D Transition state A B EA Free energy C D Reactants A B Figure 6.12 Energy profile of an exergonic reaction G  0 C D Products Progress of the reaction 22

Figure 6.13: The effect of an enzyme on activation energy Course of reaction without enzyme EA without enzyme EA with enzyme is lower Reactants Free energy Course of reaction with enzyme G is unaffected by enzyme Figure 6.13 The effect of an enzyme on activation energy Products Progress of the reaction 23

Figure 6.14: Induced fit between an enzyme and its substrate Active site Figure 6.14 Induced fit between an enzyme and its substrate Enzyme Enzyme-substrate complex 24

2 Substrates are held in active site by weak interactions. 1 Figure 6.15-4 2 Substrates are held in active site by weak interactions. 1 Substrates enter active site. Substrates Enzyme-substrate complex Active site is available for new substrates. 5 Figure 6.15-4 The active site and catalytic cycle of an enzyme (step 5) Enzyme Products are released. 4 3 Substrates are converted to products. Products 25

Effects of Local Conditions on Enzyme Activity An enzyme’s activity can be affected by: © 2014 Pearson Education, Inc. 26

Figure 6.16: Factors that affect enzyme activity Optimal temperature for typical human enzyme (37C) Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria (77C) Rate of reaction 20 40 60 80 100 120 Temperature (C) (a) Optimal temperature for two enzymes Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) Figure 6.16 Environmental factors affecting enzyme activity Rate of reaction 1 2 3 4 5 6 7 8 9 10 pH (b) Optimal pH for two enzymes 27

Cofactors and Enzyme Inhibitors What are Cofactors? What are enzyme inhibitors? Two types © 2014 Pearson Education, Inc. 28

Figure 6.17 Inhibition of Enzyme Activity (a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition Substrate Active site Competitive inhibitor Enzyme Figure 6.17 Inhibition of enzyme activity Noncompetitive inhibitor 29

Concept 6.5: Regulation of enzyme activity helps control metabolism Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated How does a cell regulate its pathways? © 2014 Pearson Education, Inc. 30

(a) Allosteric activators and inhibitors Figure 6.18a (a) Allosteric activators and inhibitors Allosteric enzyme with four subunits Active site (one of four) Regulatory site (one of four) Activator Active form Stabilized active form Oscillation Figure 6.18a Allosteric regulation of enzyme activity (part 1: activation and inhibition) Non- functional active site Inhibitor Inactive form Stabilized inactive form 31

Stabilized active form Figure 6.18b (b) Cooperativity: another type of allosteric activation Substrate Figure 6.18b Allosteric regulation of enzyme activity (part 2: cooperativity) Inactive form Stabilized active form 32

Feedback Inhibition In feedback inhibition, the end product of a metabolic pathway shuts down the pathway WHY is it important? © 2014 Pearson Education, Inc. 33

Figure 6.19 Feedback Inhibition Active site available Threonine in active site Enzyme 1 (threonine deaminase) Isoleucine used up by cell Intermediate A Feedback inhibition Enzyme 2 Intermediate B Enzyme 3 Intermediate C Isoleucine binds to allosteric site. Figure 6.19 Feedback inhibition in isoleucine synthesis Enzyme 4 Intermediate D Enzyme 5 End product (isoleucine) 34

Mitochondria The matrix contains enzymes in solution Figure 6.20 Mitochondria The matrix contains enzymes in solution that are involved in one stage of cellular respiration. Enzymes for another stage of cellular respiration are embedded in the inner membrane. Figure 6.20 Organelles and structural order in metabolism 1 m 35