METABOLISM Chapter 6

WHAT IS ENERGY? Energy is the capacity to cause change Energy exists in various forms, some of which can perform work 2

FORMS OF ENERGY Kinetic energy energy associated with motion Thermal energy kinetic energy associated with random movement of atoms or molecules Heat thermal energy in transfer from one object to another 3

FORMS OF ENERGY Potential energy energy that matter possesses because of its location or structure Chemical energy potential energy available for release in a chemical reaction Energy can be converted from one form to another 4

The Laws of Energy Transformation Thermodynamics the study of energy transformations An isolated system, such as that approximated by liquid in a thermos, is isolated from its surroundings In an open system, energy and matter can be transferred between the system and its surroundings Organisms are open systems 5

(a) An isolated hydroelectric system Figure 6.7a G  0 G  0 Figure 6.7a Equilibrium and work in isolated and open systems (part 1: isolated system) (a) An isolated hydroelectric system 6

(b) An open hydroelectric system G  0 Figure 6.7b Figure 6.7b Equilibrium and work in isolated and open systems (part 2: open system) 7

The First Law of Thermodynamics 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 The first law is also called the principle of conservation of energy 8

(a) First law of thermodynamics Figure 6.3a Chemical energy Figure 6.3a The two laws of thermodynamics (part 1: conservation of energy) (a) First law of thermodynamics 9

The Second Law of Thermodynamics During every energy transfer or transformation, some energy is unusable and is often lost as heat According to the second law of thermodynamics Every energy transfer or transformation increases the entropy of the universe Entropy is a measure of disorder, or randomness 10

(b) Second law of thermodynamics Figure 6.3b Heat Figure 6.3b The two laws of thermodynamics (part 2: entropy) (b) Second law of thermodynamics 11

ONE-WAY FLOW OF ENERGY The sun is life’s primary energy source Producers trap energy from the sun and convert it into chemical bond energy All organisms use the energy stored in the bonds of organic compounds to do work 12

Overview: The Energy of Life The living cell is a miniature chemical factory where thousands of reactions occur The cell extracts energy and applies energy to perform work Metabolism is the totality of an organism’s chemical reactions Metabolism is an emergent property of life that arises from interactions between molecules within the cell 13

Metabolic Pathways A metabolic pathway begins with a specific molecule and ends with a product Each step is catalyzed by a specific enzyme Figure 6.UN01 In-text figure, metabolic pathway schematic, p. 116 Enzyme 1 Enzyme 2 Enzyme 3 Starting molecule A B C D Product Reaction 1 Reaction 2 Reaction 3 14

Free-Energy Change (G), Stability, and Equilibrium A living system’s free energy is energy that can do work when temperature and pressure are uniform, as in a living cell The change in free energy (∆G) during a chemical reaction is the difference between the free energy of the final state and the free energy of the initial state ∆G = Gfinal state – Ginitial state Only processes with a negative ∆G are spontaneous Spontaneous processes can be harnessed to perform work 16

Metabolic Pathways 2 types Catabolic degradative process exergonic reaction respiration products have less energy than starting substance Metabolic Pathways glucose, a high energy starting substance + 6O2 ENERGY OUT 6 6 low energy products 17

Exergonic Reactions in Metabolism An exergonic reaction proceeds with a net release of free energy and is spontaneous; ∆G is negative The magnitude of ∆G represents the maximum amount of work the reaction can perform 18

Amount of energy released (G  0) Figure 6.6a (a) Exergonic reaction: energy released, spontaneous Reactants Amount of energy released (G  0) Energy Free energy Products Figure 6.6a Free energy changes (ΔG) in exergonic and endergonic reactions (part 1: exergonic) Progress of the reaction 19

Biosynthetic pathways involve the building of complicated molecules Anabolic Biosynthetic pathways involve the building of complicated molecules endergonic reaction “uphill” reaction photosynthesis glucose, a high energy product + 6O2 ENERGY IN low energy starting substances 6 6 20

Endergonic Reactions in Metabolism An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous; ∆G is positive The magnitude of ∆G is the quantity of energy required to drive the reaction 21

Amount of energy required (G  0) (b) Endergonic reaction: energy required, nonspontaneous Products Amount of energy required (G  0) Energy Free energy Reactants Figure 6.6b Free energy changes (ΔG) in exergonic and endergonic reactions (part 2: endergonic) Progress of the reaction 22

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 defining feature of life is that metabolism is never at equilibrium 23

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ATP A cell does three main kinds of work Chemical Transport Mechanical To do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic one Most energy coupling in cells is mediated by ATP 26

The Structure and Hydrolysis of ATP ATP (adenosine triphosphate) is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups In addition to its role in energy coupling, ATP is also used to make RNA ATP Formation 27

(a) The structure of ATP Adenine Phosphate groups Ribose Figure 6.8a The structure and hydrolysis of adenosine triphosphate (ATP) (part 1: structure) (a) The structure of ATP 28

Adenosine triphosphate (ATP) Figure 6.8b The structure and hydrolysis of adenosine triphosphate (ATP) (part 2: hydrolysis) Energy Inorganic phosphate Adenosine diphosphate (ADP) (b) The hydrolysis of ATP 29

How the Hydrolysis of ATP Performs Work The three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction Overall, the coupled reactions are exergonic 30

GGlu  3.4 kcal/mol Glutamic acid Ammonia Glutamine (a) Glutamic acid conversion to glutamine Figure 6.9a How ATP drives chemical work: energy coupling using ATP hydrolysis (part 1: a nonspontaneous reaction) 31

Phosphorylated intermediate Phosphorylated intermediate Glutamic acid Phosphorylated intermediate Figure 6.9b How ATP drives chemical work: energy coupling using ATP hydrolysis (part 2: phosphorylation) Phosphorylated intermediate Glutamine (b) Conversion reaction coupled with ATP hydrolysis 32

(c) Free-energy change for coupled reaction G  −3.9 kcal/mol Net GGlu  3.4 kcal/mol GGlu  3.4 kcal/mol GATP  −7.3 kcal/mol GATP  −7.3 kcal/mol  Figure 6.9c How ATP drives chemical work: energy coupling using ATP hydrolysis (part 3: coupled free energy) (c) Free-energy change for coupled reaction G  −3.9 kcal/mol Net 33

The recipient molecule is now called a phosphorylated intermediate ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant The recipient molecule is now called a phosphorylated intermediate ATP hydrolysis leads to a change in a protein’s shape and often its ability to bind to another molecule 34

Protein and vesicle moved 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. 35

Mitochondrial chemiosmosis ATP/ADP Cycle Mitochondrial chemiosmosis

The Regeneration of ATP ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP) phosphorylation The energy to phosphorylate ADP comes from catabolic reactions in the cell The ATP cycle is a revolving door through which energy passes during its transfer from catabolic to anabolic pathways 37

Energy from catabolism (exergonic, energy- releasing processes) Energy for cellular work (endergonic, energy-consuming processes) Figure 6.11 The ATP cycle 38

reactions that release energy reactions that require energy ATP/ADP Cycle ATP cellular work (e.g., synthesis, breakdown, or rearrangement of substances; contraction of muscle cells; active transport across a cell membrane) ATP reactions that release energy reactions that require energy ADP + Pi 39

ENZYME STRUCTURE AND FUNCTION A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction An enzyme is a catalytic protein 40

4 FEATURES OF ENZYMES 1) Enzymes do not make anything happen that could not happen on its own. They just make it happen much faster. 2) Reactions do not alter or use up enzyme molecules. 3) The same enzyme usually works for both the forward and reverse reactions. 4) Each type of enzyme recognizes and binds to only certain substrates. 41

The Activation Energy Barrier Every chemical reaction between molecules involves bond breaking and bond forming The initial energy needed to start a chemical reaction is called the free energy of activation, or activation energy (EA) Activation energy is often supplied in the form of thermal energy that the reactant molecules absorb from their surroundings 42

Progress of the 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 43

How Enzymes Speed Up Reactions Enzymes catalyze reactions by lowering the EA barrier Enzymes do not affect the change in free energy (∆G); instead, they hasten reactions that would occur eventually © 2014 Pearson Education, Inc. 44

Activation Energy Activation energy

Progress of the reaction 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 46

Substrate Specificity of Enzymes The reactant that an enzyme acts on is called the enzyme’s substrate The enzyme binds to its substrate, forming an enzyme-substrate complex The active site is the region on the enzyme where the substrate binds Enzyme specificity results from the complementary fit between the shape of its active site and the substrate shape 47

Enzymes change shape due to chemical interactions with the substrate This induced fit of the enzyme to the substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction 48

Catalysis in the Enzyme’s Active Site In an enzymatic reaction, the substrate binds to the active site of the enzyme The active site can lower an EA barrier by Orienting substrates correctly Straining substrate bonds Providing a favorable microenvironment Covalently bonding to the substrate 49

Substrates are 2 Substrates enter 1 held in active site by weak interactions. 1 Substrates enter active site. Substrates Enzyme-substrate complex Figure 6.15-1 The active site and catalytic cycle of an enzyme (steps 1-2) 50

Substrates are 2 Substrates enter 1 held in active site by weak interactions. 1 Substrates enter active site. Substrates Enzyme-substrate complex Figure 6.15-2 The active site and catalytic cycle of an enzyme (step 3) 3 Substrates are converted to products. 51

2 Substrates are held in active site by weak interactions. 1 Substrates enter active site. Substrates Enzyme-substrate complex Figure 6.15-3 The active site and catalytic cycle of an enzyme (step 4) Products are released. 4 3 Substrates are converted to products. Products 52

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 53

ENZYME HELPERS Cofactors Coenzymes (organic) NAD+, NADP+, FAD Accept electrons and hydrogen ions; transfer them within cell Derived from vitamins Metal ions Ferrous iron in cytochromes 54

Enzyme Inhibitors Competitive inhibitors bind to the active site of an enzyme, competing with the substrate Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effective Examples of inhibitors include toxins, poisons, pesticides, and antibiotics Competitive vs Non-Competititve Inhibition 55

(b) Competitive inhibition (c) Noncompetitive inhibition (a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition Substrate Active site Competitive inhibitor Enzyme Figure 6.17 Inhibition of enzyme activity Noncompetitive inhibitor 56

The Evolution of Enzymes Enzymes are proteins encoded by genes Changes (mutations) in genes lead to changes in amino acid composition of an enzyme Altered amino acids in enzymes may alter their substrate specificity Under new environmental conditions a novel form of an enzyme might be favored 57

Regulation of enzyme activity helps control metabolism Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated A cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes 58

Allosteric Regulation of Enzymes may either inhibit or stimulate an enzyme’s activity occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site 59

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 60

Allosteric Activation

ALLOSTERIC ACTIVATION allosteric activator enzyme active site vacant allosteric binding site active site cannot bind substrate active site altered, can bind substrate 62

Allosteric Inhibition

ALLOSTERIC INHIBITION allosteric inhibitor allosteric binding site vacant; active site can bind substrate active site altered, can’t bind substrate 64

Feedback Inhibition Feedback Inhibition the end product of a metabolic pathway shuts down the pathway prevents a cell from wasting chemical resources by synthesizing more product than is needed 65

END PRODUCT (tryptophan) FEEDBACK INHIBITION enzyme 2 enzyme 3 enzyme 4 enzyme 5 A cellular change, caused by a specific activity, shuts down the activity that brought it about enzyme 1 END PRODUCT (tryptophan) SUBSTRATE 67

ENZYME WEBSITES Enzyme Definitions Active Site Enzymes and Reactions Enzyme Action (fats, carbs, proteins) peristalsis / chyme 68

FACTORS INFLUENCING ENZYME ACTIVITY Temperature pH Salt concentration Allosteric regulators Coenzymes and cofactors 69

EFFECT OF TEMPERATURE Small increase in temperature increases molecular collisions, reaction rates High temperatures disrupt bonds and destroy the shape of active site 70

Optimal temperature for typical human enzyme (37C) enzyme of thermophilic (heat-tolerant) bacteria (77C) Rate of reaction Figure 6.16a Environmental factors affecting enzyme activity (part 1: temperature) 20 40 60 80 100 120 Temperature (C) Optimal temperature for two enzymes 71

Enzymes and temperature Effect of Temperature Enzymes and temperature

Optimal pH for two enzymes Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) Rate of reaction Figure 6.16b Environmental factors affecting enzyme activity (part 2: pH) 1 2 3 4 5 6 7 8 9 10 pH Optimal pH for two enzymes 73

ALCOHOL, ENZYMES, AND YOUR LIVER Catalase is an enzyme that helps the body break down toxic substances in alcoholic drinks 74

The liver plays a central role in alcohol metabolism Consumption of too much alcohol, as in binge drinking, can lead to alcoholic hepatitis or alcoholic cirrhosis 75

Alcohol, Enzymes, and Your Liver

REDOX REACTIONS Cells release energy efficiently by electron transfers, or oxidation-reduction reactions (“redox” reactions) Oxidation (oxidized) one molecule gives up electrons Reduction (reduced) another molecule gains electrons Hydrogen atoms are commonly released at the same time, thus becoming H+ 77

ELECTRON TRANSFER CHAINS Arrangement of enzymes, coenzymes, at cell membrane As one molecule is oxidized, next is reduced Function in aerobic respiration and photosynthesis 78

UNCONTROLLED VS. CONTROLLED ENERGY RELEASE H2 1/2 O2 Explosive release of energy as heat that cannot be harnessed for cellular work H2O 79