An Introduction to Metabolism 6 An Introduction to Metabolism
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 © 2014 Pearson Education, Inc. 2
Concept 6.1: An organism’s metabolism transforms matter and energy 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 © 2014 Pearson Education, Inc. 3
Metabolic Pathways A metabolic pathway begins with a specific molecule and ends with a product Each step is catalyzed by a specific enzyme © 2014 Pearson Education, Inc. 4
Catabolic pathways release energy by breaking down complex molecules into simpler compounds Cellular respiration is an example © 2014 Pearson Education, Inc. 5
The synthesis of protein from amino acids is an example of anabolism Anabolic pathways consume energy to build complex molecules from simpler ones The synthesis of protein from amino acids is an example of anabolism Bioenergetics is the study of how organisms manage their energy resources © 2014 Pearson Education, Inc. 6
Forms of Energy Bioenergetics is the study of how organisms manage their energy resources Energy is the capacity to cause change © 2014 Pearson Education, Inc. 7
Kinetic energy is energy associated with motion Energy exists in various forms, some of which can perform work Kinetic energy is energy associated with motion Thermal energy is kinetic energy associated with random movement of atoms or molecules Heat is thermal energy in transfer from one object to another Potential energy is energy that matter possesses because of its location or structure © 2014 Pearson Education, Inc. 8
Energy can be converted from one form to another Chemical energy is potential energy available for release in a chemical reaction Energy can be converted from one form to another © 2014 Pearson Education, Inc. 9
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. 10
The Laws of Energy Transformation Thermodynamics is 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 © 2014 Pearson Education, Inc. 11
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 © 2014 Pearson Education, Inc. 12
also called the principle of conservation of energy Figure 6.3a Chemical energy Figure 6.3a The two laws of thermodynamics (part 1: conservation of energy) (a) First law of thermodynamics also called the principle of conservation of energy 13
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 © 2014 Pearson Education, Inc. 14
Entropy is a measure of disorder, or randomness = CHAOS
Living cells unavoidably convert organized forms of energy to heat Figure 6.3b Heat Figure 6.3b The two laws of thermodynamics (part 2: entropy) (b) Second law of thermodynamics Living cells unavoidably convert organized forms of energy to heat 16
Spontaneous processes occur without energy input For a process to occur without energy input, it must increase the entropy of the universe © 2014 Pearson Education, Inc. 17
Biological Order and Disorder Cells create ordered structures from less ordered materials © 2014 Pearson Education, Inc. 18
Figure 6.4 Order as a characteristic of life Organisms also replace ordered forms of matter and energy with less ordered forms 19
Heat Figure 1.9 Energy flow and chemical cycling Energy flows into an ecosystem in the form of light and exits in the form of heat 20
Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases © 2014 Pearson Education, Inc. 21
Attendance
Concept 6.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously Biologists want to know which reactions occur spontaneously and which require input of energy To do so, they need to determine energy changes that occur in chemical reactions © 2014 Pearson Education, Inc. 23
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 G © 2014 Pearson Education, Inc. 24
∆G = Gfinal state – Ginitial state 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 © 2014 Pearson Education, Inc. 25
Free energy is 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 At equilibrium, forward and reverse reactions occur at the same rate; it is a state of maximum stability A process is spontaneous and can perform work only when it is moving toward equilibrium © 2014 Pearson Education, Inc. 26
More free energy (higher G) Less stable Greater work capacity Figure 6.5a 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 6.5a The relationship of free energy to stability, work capacity, and spontaneous change (part 1: free energy and spontaneity) Less free energy (lower G) More stable Less work capacity 27
(a) Gravitational motion (b) Diffusion (c) Chemical reaction Figure 6.5b Figure 6.5b The relationship of free energy to stability, work capacity, and spontaneous change (part 2: gravitational motion, diffusion, and chemical reaction) (a) Gravitational motion (b) Diffusion (c) Chemical reaction 28
Free Energy and Metabolism The concept of free energy can be applied to the chemistry of life’s processes © 2014 Pearson Education, Inc. 29
Exergonic and Endergonic 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 © 2014 Pearson Education, Inc. 30
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 31
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 © 2014 Pearson Education, Inc. 32
Amount of energy required (G 0) Figure 6.6b (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 33
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 © 2014 Pearson Education, Inc. 34
Closed and open hydroelectric systems can serve as analogies A catabolic pathway in a cell releases free energy in a series of reactions Closed and open hydroelectric systems can serve as analogies © 2014 Pearson Education, Inc. 35
(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 36
(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) 37
(c) A multistep open hydroelectric system Figure 6.7c G 0 G 0 G 0 Figure 6.7c Equilibrium and work in isolated and open systems (part 3: multistep system) (c) A multistep open hydroelectric system 38
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 © 2014 Pearson Education, Inc. 39
Most energy coupling in cells is mediated by ATP 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 © 2014 Pearson Education, Inc. 40
Top Hat Question 1
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 © 2014 Pearson Education, Inc. 42
(a) The structure of ATP Figure 6.8a Adenine Phosphate groups Ribose Figure 6.8a The structure and hydrolysis of adenosine triphosphate (ATP) (part 1: structure) (a) The structure of ATP 43
Adenosine triphosphate (ATP) Figure 6.8b 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 44
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 © 2014 Pearson Education, Inc. 45
GGlu 3.4 kcal/mol Glutamic acid Ammonia Glutamine Figure 6.9a Glutamic acid Ammonia Glutamine GGlu 3.4 kcal/mol (a) Glutamic acid conversion to glutamine Figure 6.9a How ATP drives chemical work: energy coupling using ATP hydrolysis (part 1: a nonspontaneous reaction) 46
Phosphorylated intermediate Phosphorylated intermediate Figure 6.9b 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 47
(c) Free-energy change for coupled reaction G −3.9 kcal/mol Net Figure 6.9c 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 48
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 © 2014 Pearson Education, Inc. 49
Protein and vesicle moved Figure 6.10 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. 50
The Regeneration of ATP ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP) The energy to phosphorylate ADP comes from catabolic reactions in the cell 51
Concept 6.4: Enzymes speed up metabolic reactions by lowering energy barriers A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction An enzyme is a catalytic protein © 2014 Pearson Education, Inc. 52
Figure 6.UN02 Sucrase Sucrose (C12H22O11) Glucose (C6H12O6) Fructose (C6H12O6) Figure 6.UN02 In-text figure, hydrolysis of sucrose, p. 125 Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction 53
The Activation Energy Barrier Chemical reactions involve 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 © 2014 Pearson Education, Inc. 54
The initial energy needed to start a chemical reaction is called the free energy of activation, or activation energy (EA) Often supplied in the form of thermal energy that the reactant molecules absorb from their surroundings
Progress of the reaction Figure 6.12 A 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 56
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. 57
Animation: How Enzymes Work Right click slide / Select play 58
Progress of the reaction Figure 6.13 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 59
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 © 2014 Pearson Education, Inc. 60
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 © 2014 Pearson Education, Inc. 61
Substrate Active site Enzyme Enzyme-substrate complex Figure 6.14 Figure 6.14 Induced fit between an enzyme and its substrate Enzyme Enzyme-substrate complex 62
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 © 2014 Pearson Education, Inc. 63
Substrates are 2 Substrates enter 1 held in active site by Figure 6.15-1 2 Substrates are 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) 64
Substrates are 2 Substrates enter 1 held in active site by Figure 6.15-2 2 Substrates are 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. 65
2 Substrates are held in active site by weak interactions. 1 Figure 6.15-3 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) 4 Products are released. 3 Substrates are converted to products. Products 66
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 67
Effects of Local Conditions on Enzyme Activity An enzyme’s activity can be affected by General environmental factors, such as temperature and pH Chemicals that specifically influence the enzyme © 2014 Pearson Education, Inc. 68
Optimal temperature for typical human enzyme (37C) Figure 6.16a Optimal temperature for typical human enzyme (37C) Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria (77C) Rate of reaction Figure 6.16a Environmental factors affecting enzyme activity (part 1: temperature) 20 40 60 80 100 120 Temperature (C) (a) Optimal temperature for two enzymes 69
(b) Optimal pH for two enzymes Figure 6.16b 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 (b) Optimal pH for two enzymes 70
Cofactors Cofactors are nonprotein enzyme helpers Cofactors may be inorganic (such as a metal in ionic form) or organic An organic cofactor is called a coenzyme Coenzymes include vitamins © 2014 Pearson Education, Inc. 71
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 © 2014 Pearson Education, Inc. 72
(b) Competitive inhibition (c) Noncompetitive inhibition Figure 6.17 (a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition Substrate Active site Competitive inhibitor Enzyme Figure 6.17 Inhibition of enzyme activity Noncompetitive inhibitor 73
Concept 6.5: 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 © 2014 Pearson Education, Inc. 74
Allosteric Regulation of Enzymes Allosteric regulation may either inhibit or stimulate an enzyme’s activity Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site © 2014 Pearson Education, Inc. 75
(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 76
Feedback Inhibition In feedback inhibition, the end product of a metabolic pathway shuts down the pathway Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed © 2014 Pearson Education, Inc. 77
End product (isoleucine) Figure 6.19 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) 78
Specific Localization of Enzymes Within the Cell Structures within the cell help bring order to metabolic pathways Some enzymes act as structural components of membranes In eukaryotic cells, some enzymes reside in specific organelles; for example, enzymes for cellular respiration are located in mitochondria © 2014 Pearson Education, Inc. 79
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 80