Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Introduction to Metabolism AP MinKnow •The key role of ATP in energy coupling. •That enzymes work by lowing the energy of activation. •The catalytic cycle of an enzyme that results in the production of a final product. •The factors that influence the efficiency of enzymes. Energy can’t be created or destroyed, but it can be transferred!!! 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 – An emergent property of life • A metabolic pathway begins with a specific molecule and ends with a product – Each step is catalyzed by a specific enzyme Enzyme 1 Enzyme 2 B A Reaction 1 Enzyme 3 C Reaction 2 D Reaction 3 Product Bioenergetics - is the study of how organisms manage their energy resources • Catabolic pathways release energy by breaking down complex molecules into simpler compounds • Anabolic pathways consume energy to build complex molecules from simpler ones Energy is the capacity to do work • Kinetic energy is energy associated with motion • Heat (thermal energy) is kinetic energy associated with random movement of atoms or molecules • 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 Animation: Energy Concepts Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Enzyme 1 A Reaction 1 Starting molecule Enzyme 2 B Enzyme 3 C Reaction 2 D Reaction 3 Product The Laws of Energy Transformation • Thermodynamics is the study of energy transformations – A closed 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings The Laws of Thermodynamics Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings We care about the 1st and 2nd laws of thermodynamics! • 1st Law of Thermodynamics • The 1st Law of Thermodyamics simply states that energy can be neither created nor destroyed (conservation of energy). – Thus power generation processes and energy sources actually involve conversion of energy from one form to another, rather than creation of energy from nothing. For example: Automobile Engine Chemical Kinetic Heater/Furnace Chemical Heat Hydroelectric Gravitational Electrical Solar Optical Electrical Nuclear Nuclear Heat, Kinetic, Optical Battery Chemical Electrical Food Chemical Heat, Kinetic Photosynthesis Optical Chemical 2nd Law of Thermodynamics (Entropy) 1. Heat flows spontaneously from a hot body to a cool one. 2. One cannot convert heat completely into useful work. 3. Everything moves towards disorder. (increasing entropy) Biological Order and Disorder 1. The evolution of more complex organisms does not violate the second law of thermodynamics 2. Entropy (disorder) may decrease in an organism, but the universe’s total entropy increases Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-3 We really care about 1st and 2nd Laws!! Heat Chemical energy (a) First law of thermodynamics CO2 + H2O (b) Second law of thermodynamics ∆G = ∆H – T∆S • ∆G – free energy in the system (J/mol) – ∆G < 0, spontaneous – ∆G > 0, non-spontaneous • ∆H - is the amount of heat released or absorbed when a chemical reaction occurs at constant pressure. (J/mol) • T – Thermal Energy (K) • ∆S – Entropy is the measure of disorder (J/K*mol) 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 • Less free energy (lower G) • More stable • Less work capacity ∆G = ∆H – T∆S Burning glucose (sugar): an exergonic reaction high high activation energy needed to ignite glucose energy content of molecules glucose + O2 energy released by burning glucose glucose energy content of molecules progress of reaction net energy captured by synthesizing glucose CO2 + H2O CO2 + H2O low activation energy from light captured by photosynthesis low progress of reaction Photosynthesis: an endergonic reaction • 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 motion (b) Diffusion (c) Chemical reaction Exergonic and Endergonic Reactions in Metabolism • An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous Free energy Amount of energy released (∆G < 0) Energy Products Progress of the reaction (a) Exergonic reaction: energy released Products Free energy • An exergonic reaction proceeds with a net release of free energy and is spontaneous Reactants Amount of energy required (∆G > 0) Energy Reactants Progress of the reaction (b) Endergonic reaction: energy required Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-7 ∆G < 0 ∆G = 0 (a) An isolated hydroelectric system (b) An open hydroelectric system ∆G < 0 ∆G < 0 ∆G < 0 ∆G < 0 (c) A multistep open hydroelectric system ∆G < 0 ∆G < 0 ∆G < 0 (c) A multistep open hydroelectric system Enzyme 1 A Reaction 1 Starting molecule Enzyme 2 B Enzyme 3 C Reaction 2 D Reaction 3 Product • How does the second law of thermodynamics help explain the diffusion of a substance across a membrane? • Cellular respiration uses glucose and oxygen, which have high levels of free energy, and releases carbon dioxide and water, which have low levels of free energy. Is respiration spontaneous or not? Is it exergonic or endergonic? What happens to the energy released from glucose? • A key process in metabolism is the transport of hydrogen ions across a membrane to create a concentration gradient. Other processes can result in an equal concentration of hydrogen ions on each side. Which arrangement of hydrogen ions allows them to perform work in this system? The Structure and Hydrolysis of ATP • ATP (adenosine triphosphate) is the cell’s energy shuttle Adenine Phosphate groups Ribose Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-9 P P P Adenosine triphosphate (ATP) H2O Pi + Inorganic phosphate P P + Adenosine diphosphate (ADP) Energy Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions • 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-11 Membrane protein P Solute Pi Solute transported (a) Transport work: ATP phosphorylates transport proteins ADP + ATP Pi Vesicle Cytoskeletal track ATP Motor protein Protein moved (b) Mechanical work: ATP binds noncovalently to motor proteins, then is hydrolyzed Fig. 8-10 NH2 Glu Glutamic acid NH3 + ∆G = +3.4 kcal/mol Glu Ammonia Glutamine (a) Endergonic reaction 1 ATP phosphorylates glutamic acid, making the amino acid less stable. P + Glu ATP Glu + ADP NH2 2 Ammonia displaces the phosphate group, forming glutamine. P Glu + NH3 Glu + Pi (b) Coupled with ATP hydrolysis, an exergonic reaction (c) Overall free-energy change Fig. 8-12 ATP + H2O Energy from catabolism (exergonic, energy-releasing processes) ADP + P i Energy for cellular work (endergonic, energy-consuming processes) Catalysts, Enzymes, and Reactions • A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction • An enzyme is a catalytic protein Sucrose (C12H22O11) Sucrase – Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed Glucose (C H O ) 6 12 6 reaction Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fructose (C6H12O6) Fig. 8-14 A B C D Transition state A B C D EA Reactants A B ∆G < O C D Products Progress of the reaction How Enzymes Lower the EA Barrier Fig. 8-15 • 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 Course of reaction without enzyme EA without enzyme EA with enzyme is lower Reactants ∆G is unaffected by enzyme Course of reaction with enzyme Products Progress of the reaction Animation: How Enzymes Work Substrate Specificity of Enzymes • substrate - The reactant that an enzyme acts on • enzyme-substrate complex - The enzyme binds to its substrate, forming an enzymesubstrate complex • 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-16 Substrate Active site Enzyme (a) Enzyme-substrate complex (b) Catalysis in the Enzyme’s Active Site How do Enzymes Work? • 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-17 1 Substrates enter active site; enzyme changes shape such that its active site enfolds the substrates (induced fit). 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. Substrates Enzyme-substrate complex 6 Active site is available for two new substrate molecules. Enzyme 5 Products are released. 4 Substrates are converted to products. Products 3 Active site can lower EA and speed up a reaction. – – General environmental factors, such as temperature and pH Chemicals that specifically influence the enzyme (cofactor) • Coenzyme Optimal temperature for enzyme of thermophilic (heat-tolerant) bacteria 40 60 80 Temperature (ºC) (a) Optimal temperature for two enzymes 0 20 Optimal pH for pepsin (stomach enzyme) 100 Optimal pH for trypsin (intestinal enzyme) Rate of reaction • An enzyme’s activity can be affected by Rate of reaction Optimal temperature for typical human enzyme 4 5 pH (b) Optimal pH for two enzymes 0 1 2 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 3 6 7 8 9 10 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-19 Substrate Active site Competitive inhibitor Enzyme Noncompetitive inhibitor (a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition Enzyme Inhibitors • Competitive inhibitors bind to the active site of an enzyme, competing with the substrate • Noncompetitive inhibitors (Allosteric 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 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 • Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site Allosteric enzyme with four subunits Active site (one of four) Regulatory site (one of four) Activator Active form Stabilized active form Oscillation NonInhibitor functional Inactive form active site (a) Allosteric activators and inhibitors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Stabilized inactive form Identification of Allosteric Regulators (Your Drugs!!!) • Allosteric regulators are attractive drug candidates for enzyme regulation • Inhibition of proteolytic enzymes called caspases may help management of inappropriate inflammatory responses Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 8-21 EXPERIMENT Caspase 1 Active site Substrate SH Known active form SH Active form can bind substrate SH Allosteric binding site Allosteric Known inactive form inhibitor S–S Hypothesis: allosteric inhibitor locks enzyme in inactive form RESULTS Caspase 1 Active form Inhibitor Allosterically Inactive form inhibited form Fig. 8-21b RESULTS Caspase 1 Active form Inhibitor Allosterically Inactive form inhibited form Feedback Inhibition Fig. 8-22 • 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 Initial substrate (threonine) Active site available Isoleucine used up by cell Threonine in active site Enzyme 1 (threonine deaminase) Intermediate A Feedback inhibition Isoleucine binds to allosteric site Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Enzyme 2 Active site of enzyme 1 no longer binds Intermediate B threonine; pathway is Enzyme 3 switched off. Intermediate C Enzyme 4 Intermediate D Enzyme 5 End product (isoleucine)