Chapter 8: An Introduction to Metabolism Mrs. Valdes AP Biology

Overview: The Energy of Life Living cell = miniature chemical factory where thousands of reactions occur Cell extracts energy  applies it to perform work Some organisms convert energy  light, bioluminescence

Organization of the Chemistry of Life into Metabolic Pathways Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics Metabolism: totality of organism’s chemical reactions an emergent property of life that arises from interactions between molecules within the cell Organization of the Chemistry of Life into Metabolic Pathways Metabolic pathway: begins with specific molecule and ends with a product Each step catalyzed by a specific enzyme

Organization of the Chemistry of Life into Metabolic Pathways Catabolic pathways: release energy by breaking down complex molecules into simpler compounds Ex: Cellular respiration= the breakdown of glucose in the presence of oxygen Anabolic pathways: consume energy to build complex molecules from simpler ones Ex: synthesis of protein from amino acids Bioenergetics: study of how organisms manage their energy resources

Forms of Energy Kinetic energy: energy associated with motion Energy: the capacity to cause change exists in various forms, some can perform work Kinetic energy: energy associated with motion Heat (thermal energy): kinetic energy associated with random movement of atoms or molecules 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

Fig. 8-2 A diver has more potential energy on the platform than in the water. Diving converts potential energy to kinetic energy. Figure 8.2 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 than on the platform.

The Laws of Energy Transformation Thermodynamics: study of energy transformations Closed system is isolated from its surroundings Ex: liquid in a thermos, In open system energy and matter can be transferred between the system and its surroundings Ex: Organisms! Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The First Law of Thermodynamics First law of thermodynamics: energy of the universe is constant: – Energy can be transferred and transformed, but it cannot be created or destroyed Also called the principle of conservation of energy

The Second Law of Thermodynamics Second law of thermodynamics: during every energy transfer or transformation, some energy is unusable, and is often lost as heat Every energy transfer or transformation increases the entropy (disorder) of the universe Living cells unavoidably convert organized energy forms  heat Spontaneous processes occur without energy input quickly or slowly For a process to occur without energy input, it must increase the entropy of universe

(a) First law of thermodynamics (b) Second law of thermodynamics Fig. 8-3 Heat CO2 + Chemical energy H2O Figure 8.3 The two laws of thermodynamics (a) First law of thermodynamics (b) Second law of thermodynamics

Biological Order and Disorder Cells create ordered structures from less ordered materials Organisms replace ordered forms of matter and energy with less ordered forms Energy: Flows into an ecosystem as light and Exits as heat Explain this. Evolution of more complex organisms does not violate the second law of thermodynamics Why not? Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Root of buttercup plant; Fig. 8-4 Root of buttercup plant; As open system, plants can increase their order as long as order of surroundings decrease Figure 8.4 Order as a characteristic of life 50 µm

Concept 8.2: 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 THUS! they need to determine energy changes that occur in chemical reactions

Free-Energy Change, G Free energy: energy that can do work when temperature and pressure are uniform like in a living cell Change in free energy (∆G) during a process is related to change in enthalpy/change in total energy (∆H), change in entropy (∆S), and temperature in Kelvin (T): ∆G = ∆H – T∆S Only processes with a negative ∆G are spontaneous Spontaneous processes can be harnessed to perform work Can you think of one? Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Free Energy, Stability, and Equilibrium Free energy is a measure of a system’s instability or its tendency to change to a more stable state During spontaneous change: free energy decreases stability of system increases Equilibrium: state of maximum stability A process is spontaneous and can perform work only when it is moving toward equilibrium

Fig. 8-5 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 Less free energy (lower G) More stable Less work capacity Figure 8.5 The relationship of free energy to stability, work capacity, and spontaneous change (a) Gravitational motion (b) Diffusion (c) Chemical reaction

More free energy (higher G) Less stable Greater work capacity Fig. 8-5a 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 8.5 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 Fig. 8-5b Spontaneous change Spontaneous change Spontaneous change Figure 8.5 The relationship of free energy to stability, work capacity, and spontaneous change (a) Gravitational motion (b) Diffusion (c) Chemical reaction

Free Energy and Metabolism Concept of free energy can be applied to chemistry of life’s processes Exergonic reaction: net release of free energy; spontaneous Endergonic reaction: absorbs free energy from its surroundings; nonspontaneous

Amount of energy released (∆G < 0) Fig. 8-6a Reactants Amount of energy released (∆G < 0) Free energy Energy Products Figure 8.6a Free energy changes (ΔG) in exergonic and endergonic reactions Progress of the reaction (a) Exergonic reaction: energy released

Amount of energy required (∆G > 0) Fig. 8-6b Products Amount of energy required (∆G > 0) Energy Free energy Reactants Figure 8.6b Free energy changes (ΔG) in exergonic and endergonic reactions Progress of the reaction (b) Endergonic reaction: energy required

Equilibrium and Metabolism Reactions in closed system eventually reach equilibrium and then do no work Cells not in equilibrium; they are open systems with constant flow of materials Defining feature of life = metabolism is never at equilibrium Catabolic pathway: releases free energy in a series of reactions Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Figure 8.7 Equilibrium and work in isolated and open systems (a) An isolated hydroelectric system (b) An open hydroelectric system ∆G < 0 Figure 8.7 Equilibrium and work in isolated and open systems ∆G < 0 ∆G < 0 ∆G < 0 (c) A multistep open hydroelectric system

(a) An isolated hydroelectric system Fig. 8-7a ∆G < 0 ∆G = 0 Figure 8.7a Equilibrium and work in isolated and open systems (a) An isolated hydroelectric system

(b) An open hydroelectric system Fig. 8-7b ∆G < 0 Figure 8.7b Equilibrium and work in isolated and open systems (b) An open hydroelectric system

(c) A multistep open hydroelectric system Fig. 8-7c ∆G < 0 ∆G < 0 ∆G < 0 Figure 8.7c Equilibrium and work in isolated and open systems (c) A multistep open hydroelectric system

Cell does three main kinds of work: Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions Cell does three main kinds of work: Chemical Transport Mechanical Cells manage energy resources by energy coupling the use of an exergonic process to drive an endergonic one Most energy coupling in cells mediated by ATP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Structure and Hydrolysis of ATP ATP (adenosine triphosphate): cell’s energy shuttle ATP is composed of : ribose (a sugar) adenine (a nitrogenous base) three phosphate groups Bonds between phosphate groups of ATP’s tail can be broken by hydrolysis Energy released from ATP when terminal phosphate bond broken comes from chemical change to a state of lower free energy, not from the phosphate bonds themselves For the Cell Biology Video Space Filling Model of ATP (Adenosine Triphosphate), go to Animation and Video Files.

How ATP Performs Work Three types of cellular work (mechanical, transport, and chemical) powered by the hydrolysis of ATP In cell energy from exergonic reaction of ATP hydrolysis can be used to drive a endergonic reaction Overall: coupled reactions are exergonic ATP drives endergonic reactions by phosphorylation transferring a phosphate group to some other molecule, such as a reactant recipient molecule is now phosphorylated

∆G = +3.4 kcal/mol Glutamic acid Ammonia Glutamine Fig. 8-10 NH2 NH3 + ∆G = +3.4 kcal/mol Glu Glu Glutamic acid Ammonia Glutamine (a) Endergonic reaction 1 ATP phosphorylates glutamic acid, making the amino acid less stable. P + ATP + ADP Glu Glu NH2 P 2 Ammonia displaces the phosphate group, forming glutamine. NH3 + + P i Glu Glu Figure 8.10 How ATP drives chemical work: Energy coupling using ATP hydrolysis (b) Coupled with ATP hydrolysis, an exergonic reaction (c) Overall free-energy change

The Regeneration of ATP ATP renewable resource that is regenerated by addition of phosphate group to adenosine diphosphate (ADP) Energy to phosphorylate ADP comes from catabolic reactions in the cell Chemical potential energy temporarily stored in ATP drives most cellular work Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers Catalyst: chemical agent that speeds up a reaction without being consumed by the reaction Enzyme: catalytic protein Enzyme-catalyzed reaction Ex: Hydrolysis of sucrose by enzyme sucrase Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

The Activation Energy Barrier Every chemical reaction between molecules involves bond breaking AND bond forming Free energy of activation, or activation energy (EA): initial energy needed to start chemical reaction often supplied in form of heat from the surroundings

How Enzymes Lower the EA Barrier Enzymes catalyze reactions by lowering EA barrier Enzymes do not affect change in free energy (∆G); instead, they hasten reactions that would occur eventually

Substrate Specificity of Enzymes Substrate: reactant that an enzyme acts on Enzyme-substrate complex: formed when enzyme binds to its substrate Active site: region on the enzyme where the substrate binds Induced fit of substrate brings chemical groups of active site into positions that enhance their ability to catalyze the reaction For the Cell Biology Video Closure of Hexokinase via Induced Fit, go to Animation and Video Files.

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

Fig. 8-17 Substrates enter active site; enzyme changes shape such that its active site enfolds the substrates (induced fit). 1 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. 2 Substrates Enzyme-substrate complex Active site can lower EA and speed up a reaction. 3 Active site is available for two new substrate molecules. 6 Figure 8.17 The active site and catalytic cycle of an enzyme Enzyme 5 Products are released. Substrates are converted to products. 4 Products

Effects of Local Conditions on Enzyme Activity Enzyme’s activity can be affected by General environmental factors Temperature pH Chemicals that specifically influence enzyme

Optimal temperature for typical human enzyme Optimal temperature for Fig. 8-18 Optimal temperature for typical human enzyme Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria Rate of reaction 20 40 60 80 100 Temperature (ºC) (a) Optimal temperature for two enzymes Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) Figure 8.18 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

Cofactors Cofactors: nonprotein enzyme helpers may be inorganic (such as a metal in ionic form) or organic Coenzyme: organic cofactor include vitamins Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Enzyme Inhibitors Competitive inhibitors: bind to active site of enzyme, competing with the substrate Noncompetitive inhibitors: bind to another part of enzyme, causing enzyme to change shape and making active site less effective Examples: toxins, poisons, pesticides, and antibiotics

Noncompetitive inhibitor Fig. 8-19 Substrate Active site Competitive inhibitor Enzyme Figure 8.19 Inhibition of enzyme activity Noncompetitive inhibitor (a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition

Concept 8.5: Regulation of enzyme activity helps control metabolism Chemical chaos would result if cell’s metabolic pathways were not tightly regulated Cell does this by: switching on/off genes that encode specific enzymes regulating the activity of enzymes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

Allosteric Activation and Inhibition Most allosterically regulated enzymes made from polypeptide subunits Each enzyme has active and inactive forms Binding of activator stabilizes the active form of the enzyme Binding of inhibitor stabilizes the inactive form of the enzyme Cooperativity: form of allosteric regulation that can amplify enzyme activity binding by substrate to one active site stabilizes favorable conformational changes at all other subunits

Stabilized active form Fig. 8-20a Allosteric enzyme with four subunits Active site (one of four) Regulatory site (one of four) Activator Active form Stabilized active form Oscillation Figure 8.20a Allosteric regulation of enzyme activity Non- functional active site Inhibitor Inactive form Stabilized inactive form (a) Allosteric activators and inhibitors

(b) Cooperativity: another type of allosteric activation Fig. 8-20b Substrate Inactive form Stabilized active form Figure 8.20b Allosteric regulation of enzyme activity (b) Cooperativity: another type of allosteric activation

Identification of Allosteric Regulators Allosteric regulators = attractive drug candidates for enzyme regulation Inhibition of proteolytic enzymes called caspases may help management of inappropriate inflammatory responses

EXPERIMENT Allosteric binding site Allosteric inhibitor Caspase 1 Fig. 8-21a EXPERIMENT Caspase 1 Active site Substrate SH SH Known active form Active form can bind substrate Figure 8.21 Are there allosteric inhibitors of caspase enzymes? Allosteric binding site SH S–S Allosteric inhibitor Known inactive form Hypothesis: allosteric inhibitor locks enzyme in inactive form

RESULTS Caspase 1 Inhibitor Active form Allosterically inhibited form Fig. 8-21b RESULTS Caspase 1 Inhibitor Figure 8.21 Are there allosteric inhibitors of caspase enzymes? Active form Allosterically inhibited form Inactive form

Feedback Inhibition Feedback inhibition: end product of a metabolic pathway shuts down the pathway Prevents cell from wasting chemical resources by synthesizing more product than needed

Specific Localization of Enzymes Within the Cell Structures within cell help bring order to metabolic pathways Some enzymes act as structural components of membranes In eukaryotic cells, some enzymes reside in specific organelles Ex: enzymes for cellular respiration located in mitochondria Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

You should now be able to: Distinguish between the following pairs of terms: catabolic and anabolic pathways kinetic and potential energy open and closed systems exergonic and endergonic reactions In your own words, explain the second law of thermodynamics and explain why it is not violated by living organisms Explain in general terms how cells obtain the energy to do cellular work Explain how ATP performs cellular work Explain why an investment of activation energy is necessary to initiate a spontaneous reaction Describe the mechanisms by which enzymes lower activation energy Describe how allosteric regulators may inhibit or stimulate the activity of an enzyme

Progress of the reaction Fig. 8-UN2 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 Products Progress of the reaction