Metabolism PowerPoint PDF

An Introduction to Metabolism The Energy of Life  The living cell is a miniature chemical factory where thousands of reactions occur  Cellular respiration extracts energy stored in sugars and other fuels  Cells apply this energy to perform work  Some organisms even convert energy to light,...

An Introduction to Metabolism The Energy of Life  The living cell is a miniature chemical factory where thousands of reactions occur  Cellular respiration extracts energy stored in sugars and other fuels  Cells apply this energy to perform work  Some organisms even convert energy to light, as in bioluminescence Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics  Metabolism is the totality of an organism’s chemical reactions  Metabolism is an emergent property of life that arises from orderly interactions between molecules Organization of the Chemistry of Life into Metabolic Pathways  A metabolic pathway begins with a specific molecule and ends with a product  Each step is catalyzed by a specific enzyme  Catabolic pathways release energy by breaking down complex molecules into simpler compounds  Cellular respiration, the breakdown of glucose in the presence of oxygen, is an example of a pathway of catabolism  Anabolic pathways consume energy to build complex molecules from simpler ones  For example, the synthesis of protein from amino acids is an anabolic pathway  Bioenergetics is the study of how energy flows through living organisms Forms of Energy  Energy is the capacity to cause change  Energy exists in various forms, some of which can perform work  Kinetic energy is energy associated with motion  Thermal energy is the kinetic energy associated with random movement of atoms or molecules  Heat is thermal energy in transfer between objects  Potential energy is energy that matter possesses because of its location or structure  Chemical energy is potential energy available for release in a chemical reaction  Energy can be converted from one form to another Figure 8.2 A diver has more potential Diving converts energy on the platform potential energy to than in the water. kinetic energy. Climbing up converts the kinetic A diver has less potential energy of muscle movement energy in the water to potential energy. than on the platform. © 2017 Pearson Education, Inc. 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 unable to exchange energy or matter with its surroundings  In an open system, energy and matter can be transferred between the system and its surroundings  Organisms are open systems 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 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 molecular disorder, or randomness Figure 8.3 The two laws of thermodynamics Heat CO2 + H2O Chemical energy Kinetic in food energy (a) First law of thermodynamics (b) Second law of thermodynamics © 2017 Pearson Education, Inc.  Living cells unavoidably convert organized forms of energy to heat, a more disordered form of energy  Spontaneous processes occur without energy input; they can happen quickly or slowly  For a process to occur spontaneously, it must increase the entropy of the universe  Processes that decrease entropy are nonspontaneous; they will occur only if energy is provided Biological Order and Disorder  Organisms create ordered structures from less organized forms of energy and matter  Organisms also replace ordered forms of matter and energy in their surroundings with less ordered forms  For example, animals consume complex molecules in their food and release smaller, lower energy molecules and heat into the surroundings  The evolution of more complex organisms does not violate the second law of thermodynamics  Entropy (disorder) may decrease in a particular system, such as an organism, as long as the total entropy of the system and surroundings increases 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  To do so, they need to determine the energy and entropy changes that occur in chemical reactions Free-Energy Change, G  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 (ΔG) during a process is related to the change in enthalpy— change in total energy (ΔH)—change in entropy (ΔS), and temperature in Kelvin units (T) ΔG = ΔH − TΔS  ΔG is negative for all spontaneous processes; processes with zero or positive ΔG are never spontaneous  Spontaneous processes can be harnessed to perform work Free Energy, Stability, and Equilibrium  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  Equilibrium is a state of maximum stability  A process is spontaneous and can perform work only when it is moving toward equilibrium Figure 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 (a) Gravitational (b) Diffusion (c) Chemical motion reaction © 2017 Pearson Education, Inc. Free Energy and Metabolism  The concept of free energy can be applied to the chemistry of life’s processes Exergonic and Endergonic Reactions in Metabolism  An exergonic reaction proceeds with a net release of free energy and is spontaneous  An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous Figure 8.6 (a) Exergonic reaction: energy released, spontaneous Reactants Amount of Free energy energy released changes (ΔG) Free energy (∆G < 0) Energy in exergonic Products and endergonic Progress of the reaction reactions (b) Endergonic reaction: energy required, nonspontaneous Products Amount of energy required Free energy (∆G > 0) Energy Reactants Progress of the reaction © 2017 Pearson Education, Inc. Equilibrium and Metabolism  Reactions in a closed system eventually reach equilibrium and can 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  A catabolic pathway in a cell releases free energy in a series of reactions ∆G < 0 ∆G < 0 ∆G < 0 (b) A multistep open hydroelectric system Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions  A cell does three main kinds of work:  Chemical work—pushing endergonic reactions  Transport work—pumping substances against the direction of spontaneous movement  Mechanical work—such as contraction of muscle cells  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 The Structure and Hydrolysis of ATP  ATP (adenosine triphosphate) is the cell’s energy shuttle  ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups Figure 8.9 Adenine The structure and Triphosphate group Ribose hydrolysis of (3 phosphate groups) adenosine (a) The structure of ATP triphosphate (ATP) P P P Adenosine triphosphate (ATP) H2O P P Pi Energy Adenosine Inorganic diphosphate (ADP) phosphate (b) The hydrolysis of ATP © 2017 Pearson Education, Inc.  The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis  Energy is released from ATP when the terminal phosphate bond is broken  This release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselves 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  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 Figure 8.10 NH3 NH2 Glu ∆GGlu = +3.4 kcal/mol Glu Glutamic acid Ammonia Glutamine (a) Glutamic acid conversion to glutamine NH3 1 P 2 NH2 ADP Pi ATP ADP Glu Glu Glu Glutamic acid Phosphorylated Glutamine intermediate (b) Conversion reaction coupled with ATP hydrolysis ∆GGlu = +3.4 kcal/mol NH3 NH2 ATP ADP Pi Glu Glu ∆GGlu = +3.4 kcal/mol ∆GATP = –7.3 kcal/mol +∆GATP = –7.3 kcal/mol Net ∆G = –3.9 kcal/mol (c) Free-energy change for coupled reaction © 2017 Pearson Education, Inc.  Transport and mechanical work in the cell are also powered by ATP hydrolysis  ATP hydrolysis leads to a change in protein shape and binding ability Figure 8.11 Transport protein Solute ATP ADP Pi P Pi Solute transported (a) Transport work Vesicle Cytoskeletal track ATP ATP ADP Pi Motor protein Protein and vesicle moved (b) Mechanical work © 2017 Pearson Education, Inc. 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  The ATP cycle is a revolving door through which energy passes during its transfer from catabolic to anabolic pathways Figure 8.12 The ATP Cycle ATP H 2O Energy from Energy for cellular catabolism (exergonic, work (endergonic, energy-releasing ADP P energy-consuming processes) i processes) © 2017 Pearson Education, Inc. Concept 8.4: 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  For example, sucrase is an enzyme that catalyzes the hydrolysis of sucrose Figure 8.UN02 Sucrose Hydrolysis Sucrase H2O O HO OH Sucrose Glucose Fructose (C12H22O11) (C6H12O6) (C6H12O6) © 2017 Pearson Education, Inc. 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 Figure 8.13 Energy profile of an A B exergonic reaction C D Transition state A B EA Free energy C D Reactants A B ∆G < 0 C D Products © 2017 Pearson Education, Inc. Progress of the reaction Animation: How Enzymes Work How Enzymes Speed Up Reactions  In catalysis, enzymes or other catalysts speed up specific reactions by lowering the EA barrier  Enzymes do not affect the change in free energy (ΔG); instead, they hasten reactions that would occur eventually Figure 8.14 The effect of an enzyme on activation energy Course of reaction EA without without enzyme enzyme EA with enzyme is lower Reactants Free energy Course of ∆G is unaffected reaction by enzyme with enzyme Products Progress of the reaction © 2017 Pearson Education, Inc. 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  While bound, the activity of the enzyme converts substrate to product  The reaction catalyzed by each enzyme is very specific  The active site is the region on the enzyme where the substrate binds  Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction Figure 8.15 Induced fit between an enzyme and its substrate Substrate Active site Enzyme-substrate Enzyme complex © 2017 Pearson Education, Inc. Catalysis in the Enzyme’s Active Site  In an enzymatic reaction, the substrate binds to the active site of the enzyme  Enzymes are extremely fast acting and emerge from reactions in their original form  Very small amounts of enzyme can have huge metabolic effects because they are used repeatedly in catalytic cycles Figure 8.16_4 1 Substrates enter 2 Substrates are held active site. in active site by weak interactions. Substrates Enzyme-substrate complex 3 The active site lowers EA. 6 Active site is available for new substrates. The active site Enzyme and catalytic cycle of an enzyme 5 Products are released. 4 Substrates are converted to Products products. © 2017 Pearson Education, Inc.  The active site can lower an EA barrier by  orienting substrates correctly  straining substrate bonds  providing a favorable microenvironment  covalently bonding to the substrate  The rate of an enzyme-catalyzed reaction can be sped up by increasing substrate concentration  When all enzyme molecules have their active sites engaged, the enzyme is saturated  If the enzyme is saturated, the reaction rate can only be sped up by adding more enzyme 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 Effects of Temperature and pH  Each enzyme has an optimal temperature in which it can function  Each enzyme has an optimal pH in which it can function  Optimal conditions favor the most active shape for the enzyme molecule Figure 8.17b Environmental factors affecting enzyme activity Optimal temperature for Optimal temperature for typical human enzyme (37ºC) enzyme of thermophilic (heat-loving) bacteria (75ºC) Rate of reaction 0 20 60 40 80 100 120 Temperature (ºC) (a) Optimal temperature for two enzymes © 2017 Pearson Education, Inc. Figure 8.17c Environmental factors affecting enzyme activity Pepsin (stomach Trypsin (intestinal enzyme) enzyme) Rate of reaction 0 1 2 35 4 6 7 8 9 10 pH (b) Optimal pH for two enzymes © 2017 Pearson Education, Inc. 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 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  Some examples of inhibitors are toxins, poisons, pesticides, and antibiotics Figure 8.18 (a) Normal binding Substrate Inhibition of Active site enzyme activity Enzyme (b) Competitive inhibition Competitive inhibitor (c) Noncompetitive inhibition Noncompetitive inhibitor © 2017 Pearson Education, Inc. 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, particularly at the active site, can result in novel enzyme activity or altered substrate specificity  Under environmental conditions where the new function is beneficial, natural selection would favor the mutated allele  For example, repeated mutation and selection on the β-galactosidase enzyme in E. coli resulted in a change of sugar substrate under lab conditions Concept 8.5: 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 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 Allosteric Activation and Inhibition  Most allosterically regulated enzymes are made from polypeptide subunits, each with its own active site  The enzyme complex 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 Figure 8.20a (a) Allosteric activators and inhibitors Allosteric Allosteric Active site regulation of enzyme (one of four) enzyme activity with four subunits Regulatory site (one Activator of four) Active form Stabilized active form Oscillation Non- functional active site Inhibitor Inactive form Stabilized inactive form © 2017 Pearson Education, Inc.  Cooperativity is a form of allosteric regulation that can amplify enzyme activity  One substrate molecule primes an enzyme to act on additional substrate molecules more readily  Cooperativity is allosteric because binding by a substrate to one active site affects catalysis in a different active site Figure 8.20b Allosteric regulation of enzyme activity (b) Cooperativity: another type of allosteric activation Substrate Inactive form Stabilized active form © 2017 Pearson Education, Inc. 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 Feedback inhibition in Initial Figure 8.21 isoleucine synthesis substrate (threonine) Active site available Threonine in active site Enzyme 1 (threonine Isoleucine deaminase) used up by cell Intermediate A Feedback Active site inhibition no longer Enzyme 2 available; pathway is Intermediate B halted Enzyme 3 Intermediate C Isoleucine binds to allosteric Enzyme 4 site. Intermediate D Enzyme 5 End product (isoleucine) © 2017 Pearson Education, Inc. 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 Figure 8.22 Organelles and structural order in metabolism Mitochondrion The matrix contains enzymes in solution that are involved in the second stage of cellular respiration. Enzymes for the third stage of cellular 1 µm respiration are embedded in the inner membrane. © 2017 Pearson Education, Inc. Figure 8.UN05 Energy Conversions © 2017 Pearson Education, Inc.