Page 1 of 10 007v5 Metabolism Beavers Bio 6 CHAPTER 8 An INTRODUCTION TO METABOLISM SLIDE 1 1. QUOTE: ten important two letter words (from an amazing instructor, Dr. Follett). 2. METABOLISM A. Cells are chemical (metabolic) factories under strict control and regulation. B. Metabolism represents the totality of an organism’s chemical reactions chemical reactions. (reactions called metabolism. ) C. It is an emergent property (intermolecular force emergent property) arising from ordered molecular interactions. D. Artist's image: First steps of glycolysis seen amongst the thousands of chemical reactions that can occur in a cell. SLIDE 2 3. METABOLISM is energy use and energy acquisition. A. Energy Example: Ruby throated hummingbird. B. ENERGY EXAMPLE: IMAGE: Ruby-throated hummingbird. C. Wings beat 60 times per second D. Has a metabolic rate 50x that of a human being. Its muscles are packed with Mitochondria. Why? Produces E. ATP the energy required for muscle movement. 4. METABOLISM definition A. Metabolism: the totality of an organism’s chemical reactions, consisting of catabolic and anabolic pathways, which manage the material and energy resources of the organism. SLIDE 3 5. WORK requires ENERGY A. WORK REQUIRES ENERGY (don't we know it in Bio 6!). B. Energy is defined as the CAPACITY to cause CHANGE. C. What is cell work? Two examples: 1. Transporting substances across membranes. 2. Moving substances along the cyctoskeletol track. ____________________________________________________________ a. Can you think of other examples of cell work? SLIDE 4 2. WILD EXAMPLE OF ENERGY: BIOLUMINESCENCE: Dinoflagellates convert energy stored in certain organic molecules to light: a. Research from UCSD: Dinoflagellate flashes cause a startle response in their predators, disrupting their feeding behavior and resulting in a decrease in grazing rate by reducing the number of dinoflagellates consumed. b. Dinoflagellate bioluminescence is also thought to act as a “burglar alarm” to attract a secondary predator that threatens to eat the primary predator.” Slide 5 3. METABOLISM: the totality of an organism's chemical reactions. a. Metabolism is an EMERGENT PROPERTY that arises from orderly interactions between MOLECULES. Page 2 of 10 007v5 Metabolism Beavers Bio 6 b. Metabolic pathway: A series of chemical reactions that either builds a complex molecule (anabolic pathway) or breaks down a complex molecule into simpler compounds ( catabolic pathway). c. IMAGE: Krebs cycle (a.k.a. citric acid cycle) an 8-step pathway to complete the breakdown of glucose in cellular respiration. Each step of pathway is catalyzed by a specific enzyme. Slide 6 4. CHEMICAL REACTIONS ORGANIZED INTO METABOLIC PATHWAYS a. Metabolic pathways begin with a SPECIFIC STARTING molecule that is ALTERED to produce a specific product. b. Each step of the pathway is catalyzed by a specific enzyme. Slide 7 9.9 5. METABOLISM- Degradative Processes a. Catabolic pathways: A metabolic pathway that release energy by breaking down complex molecules to simpler compounds. b. "Downhill reactions." c. A major pathway of catabolism is cellular respiration. d. Energy stored in a molecule becomes available to do work: examples? e. IMAGE: Metabolic pathway showing Initial breakdown of glucose in glycolysis. Slide 8 6. METABOLISM-Biosynthetic Pathways a. Anabolic pathways: a metabolic pathway that consumes energy to synthesize a complex molecule from simpler compounds. b. "Uphill reactions." c. Examples: Building amino acids from molecules and then building polypeptide chain from amino acids. Slide 9 7. ENERGY: The capacity to cause change. a. Biologists study how energy flows in living organisms, or bioenergetics. b. Definition: The [study of the] overall flow and transformation of energy in an organism. c. Energy form examples in this image: d. Kinetic energy. e. Potential energy. 8. ENERGY: Two principle forms Slide 10 Kinetic 1. Thermal 2. Light 3. Mechanical energy 4. Electrical energy Potential 1. Chemical 2. Concentration gradient Page 3 of 10 007v5 Metabolism Beavers Bio 6 3. Electrical membrane potential Slide 11 9. Example of Electric Energy: Membrane Potential a. membrane potential : The difference in electrical charge (voltage) across a cell’s plasma membrane, due to the differential distribution of ions. b. Membrane potential affects the activity of excitable cells and the transmembrane movement of all charged substances. c. All cells have voltages across their plasma membranes. Slide 12 10. VOLTAGE across a CELL MEMBRANE a. The cytoplasmic side of the membrane is negative in charge relative to the extracellular side due to unequal distribution of ions. b. Membrane potential ranges from -50 to -200 millivolts (mV), minus sign indicates that the inside of the cell is negative relative to outside. Slide 13 11. Membrane Potential a. Membrane potential acts like a battery…an energy source. b. Membrane potential favors passive transport of positive ions into the cell (where it is relatively positive) and negative ions out of the cell (where it is relatively negative. c. This drives the diffusion of ions across the membrane. Slide 14 12. ELECTROCHEMICAL GRADIENT-the passive transport of an ion a. Electrochemical gradient: The diffusion gradient of an ion, which is affected by both the concentration gradient of the ion across a membrane (a chemical force) and the ion’s tendency to move relative to the membrane potential or voltage (an electrical force). b. New definition of ion diffusion: An ion diffuses down its electrochemical gradient. c. Gradients are energy sources. Slide 15 13. ENERGY: Helpful Definitions a. Energy: the capacity to cause change, especially to do work (to move matter against an opposing force). b. Kinetic energy: The energy associated with the relative motion of objects. Moving matter can perform work by imparting motion to other matter. c. Thermal Energy: The total amount of kinetic energy due to the random motion of atoms or molecules in a body of matter. Thermal energy in transfer from one object to another is called HEAT. Heat is energy is its most random form. d. Light energy can also be harnessed to perform work. 14. ENERGY: Helpful Definitions a. Potential Energy: that is not kinetic. It is the energy that matter possesses as a result of its location or spatial arrangement (structure). Page 4 of 10 007v5 Metabolism Beavers Bio 6 b. Chemical Energy: is a type of potential energy available in molecules for release in a chemical reaction. c. When energy is released in a chemical reaction, it is the result of matter (atoms) BEING REARRANGED!!! Slide 16 d. Matter atoms ) When rearranged, high energy molecules produce low energy PRODUCTS and RELEASE ENERGY in a living organism. e. Example: IN cellular respiration in a living organism. HIGH ENERGY MOLECULES PRODUCE LOW ENERGY PRODUCTS AND RELEASE ENERGY IN A LIVING ORGANISM. f. Organisms are energy transformers. Slide 17 15. LAWS OF THERMODYNAMICS GOVERN ENERGY TRANSFORMATIONS a. Even in this non-living example, POTENTIAL ENERGY BY POSTION (water behind a dam) is TRANSFORMED into KINETIC energy (releasing the water from the dam) that performs WORK (moves turbines to produce electricity). b. Thermodynamics is the study of energy transformations that occur in the collection of matter. c. What is the source of energy for human beings? FOOD Slide 18 16. THERMODYNAMICS – Laws that govern energy transformations: a. First Law of Thermodynamics: The principle of conservation of energy; Energy can be transferred and transformed, but it cannot be created or destroyed. b. System: matter under study (the bear). c. Surroundings: (universe) everything outside system. d. Example Bear: (Open system) – matter (here chemical energy) exchanged between system and surroundings. Absorb energy and then release waste and heat to the surroundings. e. OF NOTE- isolated system: no exchange of matter or energy with surroundings (thermos) f. Closed system: exchange energy, not matter (closed window on a sunny day). Slide 19. 8.2 17. Energy is transferred or transformed but it cannot be created or destroyed. a. IMAGE: Humans diving, swimming, climbing, waiting. 18. ENERGY TRANSFER OR TRANSFORMATION MAKES THE UNIVERSE MORE DISORDERED. a. entropy: a measure of that disorder, or randomness. b. If ENERGY cannot BE DESTROYED, WHY DO WE HAVE TO ACQUIRE NEW ENERGY? Why not recycle energy? c. The consequence of the loss of usable energy as heat to the surroundings is that each energy transfer or transformation makes the universe more disordered. Page 5 of 10 007v5 Metabolism Beavers Bio 6 d. Heat can only be put to work if there is a temperature difference that results in thermal energy flowing from warmer to cooler. Temperature is uniform in living cells. See increasing entropy surrounding the bear. d. Slide 21 19. A Law to Describe Entropy a. 2nd law of Thermodynamics: The principle stating that every energy transfer or transformation increases the entropy of the universe. Ordered forms of energy are at least partly converted to heat. cheetah b. Full stomach – fueled up with chemical energy. c. Chemical energy transformed to kinetic energy (motion). Loss of usable energy to heat, CO2 and H2O: equals an increase in entropy. 20. LAST LOOK AT ENERGY LOSS Car a. Energy transfers are never entirely efficient in living or non-living systems. b. With every transfer, some energy dissipates, and become less useful for doing work. Slide 22 21. WHY DO BIOLOGISTS CARE ABOUT ENERGY TRANSFERS? a. Biologists want to understand the chemical reactions of LIFE. b. Biologists ask questions: What reactions occur SPONTANEOUSLY (energetically favorable, without the input of energy, not necessarily quickly)? c. What reactions requires energy input? Non spontaneous d. The free-energy change of a reaction answers these questions. What is freeenergy? Slide 23 22. FREE ENERGY is a. The portion of a system’s energy that can perform work (and a measure of system instability). b. 1878 J. Willard Gibbs from Yale defined a useful function called: c. Gibbs free energy of a System (G) A way to consider the system without the surroundings (the whole universe) for every reaction: d. DEFINITION: The portion of a biological system’s energy that can perform work when temperature and pressure are uniform throughout the system (as in a cell). (The change in free energy of a system is calculated by the equation ΔG = ΔH - T ΔS, where H is enthalpy [in biological systems, equivalent to total energy], T is absolute temperature [in Kelvin’s,] and S is entropy (J/K) Slide 24 23. GIBBS FREE ENERGY CAN PERFORM WORK a. Using chemical methods, biologists can measure the change in free energy for any reaction. The free energy change (ΔG) of a reaction tells us if reaction occurs spontaneously (without input of energy). b. EXAMPLES: c. Child on a slide. d. A drop of concentrated dye is less stable than when the dye is spread randomly throughout the liquid, Page 6 of 10 007v5 Metabolism Beavers Bio 6 e. A sugar molecule is less stable (more likely to break down) than the simpler molecules into which it can be split. f. SYSTEM'S NEVER SPONTANEOUSLY MOVE AWAY FROM EQUILIBRIUM (where no work can be performed). A process is spontaneous and can perform work only when it is MOVING TOWARD Equilibrium. Slide 25 24. Why important to biologists? To predict what spontaneous reactions can be harnessed to perform work…the study of metabolism. a. Examples we will see very soon: cellular respiration and photosynthesis. b. EXAMPLE: How do bonds breaking release energy? Slide 26 Cellular respiration example. In cellular respiration of glucose transfer electrons to a lower state, LINERATING ENERGY that become available for ATP SYNTHESIS. Slide 27 25. IMPORTANT RELATIONSHIP BETWEEN FREE ENERGY AND EQUILIBRIUM a. Available free energy is like a VALLEY. b. You can roll without input of energy down into the valley (unstable; spontaneously ). c. As you roll down to the bottom of the hill (like a reaction proceeds toward equilibrium), free energy decreases. d. At the bottom of the hill, there is no free energy available (G = 0). You are very stable, no work can be done. e. Only way to get back up the hill is to climb (you are at equilibrium and cannot spontaneously change. You need energy input to climb). Slide 28 8.6 a 26. FREE ENERGY CHANGE CLASSIFICATIONS a. Exergonic Reaction: A spontaneous chemical reaction, in which there is a net release of free energy. b. EXAMPLE: Cellular respiration, traditional graph c. C6H12O6 + 6 O2 6 CO2 + 6 H2O (or ΔG) = -686 kcal/mol 27. EXERGONIC REACTIONS a. Textbook graph Slide 29 28. FREE ENERGY CHANGE CLASSIFICATIONS a. Endergonic Reaction: A non-spontaneous chemical reaction, in which free energy is absorbed from the surroundings. b. Photosynthesis: traditional graph c. 6 CO2 + 6 H2O + sunlight C6H12O6 + 6 O2 (or ΔG) = +686 kcal/mol 29. ENDERGONIC REACTIONS a. Textbook graph Slide 30 30. EQUILIBRIUM AND WORK IN ISOLATED AND OPEN SYSTEMS Page 7 of 10 007v5 Metabolism Beavers Bio 6 a. Hydroelectric system can work until it reaches equilibrium. b. Water flowing downhill prevents this hydroelectric system from reaching equilibrium. c. TRUE OR FALSE? A process is spontaneous and can perform work only when it is moving toward equilibrium. TRUE d. Is a living cell at equilibrium? NO Slide 31 31. ENERGY COUPLING a. A CELL DOES 3 MAIN KINDS OF WORK: Chemical, Transport and Mechanical. b. Energy coupling: in cellular metabolism, the use of energy released from an exergonic reaction to drive an endergonic reaction. c. Example: catabolic (exergonic) reactions provide the energy to produce ATP which drives an endergonic reaction. Slide 32 32. ATP a. ATP (adenosine triphosphate): A nucleoside triphosphate containing a ribose sugar, the nitrogenous base adenine, and a chain of three phosphate groups that releases free energy when its phosphate bonds are hydrolyzed. This energy is used to drive endergonic reactions in cells. The ATP molecule is unstable because? negative charges on the phosphate groups b. SLIDE 33 33. HOW ATP DONATES ENERGY TO DRIVE CHEMICAL WORK? phosphorylation and energy coupling a. Ex. Glutamine synthesis is endergonic (+G), requiring energy input. b. In the cell, glutamine synthesis is coupled to ATP hydrolysis, forming a phosphorylated intermediate that is UNSTABLE and more REACTIVE. c. This overall reaction is NOW spontaneous, and ΔG is negative. d. The key to coupling exergonic and endergonic reactions is the formation of the phosphorylated intermediate! Phosphorylation* Slide 34 34. Phosphorylation and dephosphorylation contribute to essential protein shape change! a. Working Muscle cell: 10 million molecules of ATP consumed and regenerated per second, per cell! Slide 35 35. ENERGY BARRIERS a. Enzymes speed up metabolic reactions by lowering energy barriers. Enzyme: a macromolecule serving as a catalyst, a chemical agent that change the rate of a reaction without being consumed by the reaction. b. Sucrose could take years to hydrolyze to glucose and fructose in sterile water without the help of an enzyme. How? Oriented the molecule To be available For hydrolysis Slide 36 36. What does sucrase do? Page 8 of 10 007v5 Metabolism Beavers Bio 6 a. Changing one molecule into another generally involves contorting the starting molecule into a highly unstable state. b. The energy required to contort reactant is known as the free energy of activation: EA. c. Metal key ring opened to add a key. Slide 37 37. WHAT IS HAPPENING WHEN MATTER CHANGES? a. Reactants must absorb enough energy to reach unstable transition state for bonds to break (called Activation Energy; EA). b. Absorption of thermal energy increases the speed of the reactant molecules…more likely to forcefully collide and react. Sometimes thermal energy isn't enough to reach transition state, seen on the graph as activation energy). c. After bonds have broken new bonds form, releasing energy to the surroundings. Slide 38 38. ACTIVATION ENERGY a. Activation energy (EA): The amount of energy that reactants must absorb before a chemical reaction will start; also called free energy of activation. b. Activation Energy is different for every reaction and is the barrier that determines the rate of a reaction! Slide 39 39. ACTIVATION ENERGY a. Room temperature can provide enough thermal energy for some reactions to take place. b. Proteins, DNA and other complex molecules are rich in free energy and have the potential to decompose spontaneously…the laws of thermodynamics favor their breakdown. 8.13 c. At temperatures typical for cells thermal energy cannot overcome the activation energy barrier. d. Increasing temperature is not appropriate for biological systems that must maintain homeostasis. HEAT WOULD SPEED UP ALL REACTIONS!!!! High temperatures denature and kill cells. How to overcome EA? Slide 40 40. CATALYSIS: when an enzyme catalyzes a reaction by lowering EA. a. Reducing EA barrier allows reactant molecules to absorb enough energy to reach the transition state even at moderate temperatures. Slide 56 41. Substrate: the reactant on which an enzyme works. a. Typically acts on 1000 substrate molecules per second.) b. Enzyme-substrate complex: A temporary complex formed when an enzyme binds to its substrate molecule(s). c. Catalytic action of enzyme converts substrate to product. Slide 57 42. INDUCED FIT a. Induced fit: Induced by entry of the substrate, the change in shape of the active site of an enzyme so that it binds more snugly to the substrate. Page 9 of 10 007v5 Metabolism Beavers Bio 6 b. Molecular shape and particular amino acids present in the active site results in specificity for a unique substrate. c. Active site will undergo a conformational change when exposed to a substrate to improve binding. 43. ENZYMES, ACTIVE SITES AND REDUCED ENERGY OF ACTIVATION a. Consider steps 1-6. b. How do enzymes accomplish the task? c. Orientation template. d. Distort substrate for transition state. e. Provides a conducive microclimate (pH?). f. Amino acids of active site may directly catalyze reaction. 44. SUBSTRATE PRODUCT a. Rate at which enzyme converts substrate to product is a FUNCTION OF: b. Initial concentration of substrate. c. Limitation of enzyme available to catalyze reaction. d. Enzyme concentration can be controlled by the cell. Slide 58 45. Effect of local conditions on enzymes…temperature, pH a. Every enzyme has an optimal temperature and pH to favor the active shape of the enzyme. b. Compare optimal temperature for typical human enzyme with heat tolerant bacteria. c. Compare optimal pH rate of reaction for typical human digestive enzymes. Stomach: pH 2, Intestine: pH 8 Slide 59 46. COFACTORS AND COENZYMES a. Some enzymes require non-protein assistance. b. Cofactor: Any nonprotein molecule or ion that is required for the proper functioning of an enzyme. Cofactors can be permanently bound to the active site or may bind loosely with the substrate during catalysis. c. Coenzymes: An organic molecule serving as a cofactor. Most vitamins function as coenzymes in metabolic reactions. Slide 60 47. ENZYME INHIBITORS: Certain chemicals selectively inhibit the action of a specific enzyme. Competitive inhibitor: a substance that reduces the activity of an enzyme by entering the active site in place of the substrate whose structure it mimics. Vs. Non competitive Inhibitor: A substance that reduces the activity of an enzyme by binding to a location remeote from the active site, changing the enzyme’s shape so that the active site no longer functions effectively. Slide 61 48. ENZYME INHIBITION: Reversible or Irreversible Page 10 of 10 007v5 Metabolism Beavers Bio 6 a. REVERSIBLE: Bind to the active site by weak interactions (non-covalent). Can represent self-regulation. b. IRREVERSIBLE: Binds with covalent interactions. c. Toxins and poisons are often irreversible. d. BAD: Sarin gas (1995 Tokyo subway terrorist attack). BINDS TO THE R GROUP OF SERINE, Found in the active site of an enzyme important in the nervous system. e. GOOD: Penicillin blocks the active site of an enzyme that many bacteria use to make their cell walls. Slide 70 49. Enzyme Regulation to Control Metabolism a. Allosteric regulation: The binding of a regulatory molecule to a protein at one site that affects the function of the protein at a different site. Most have two or more subunits with its own active site - Binding of one active site stabilized form. Slide 71 50. COOPERATIVITY a. Cooperativity: A kind of allosteric regulation whereby a shape change in one (active site of one subunit) subunit of a protein caused by substrate binding is transmitted to all the others, facilitating binding of subsequent substrate molecules. b. Cooperativity another type of allosteric activation ** If not binding to a regulatory site, (allosteric site), why allosteric regulation? Slide 72 51. FEEDBACK INHIBITION a. Threonine (amino acid) to Isoleucine (amino acid). b. Feedback inhibition: a method of metabolic control in which the end product of a metabolic pathway acts as an inhibitor of an enzyme within that pathway. Slide 73 52. ORGANELLES AND STRUCTURAL ORDER IN METABOLISM a. Organelles, like the mitochondria, have unique enzymes within them that carry out specific functions. b. This function is ESSENTIAL TO US: cellular respiration. 53. COMING UP NEXT: CELLULAR RESPIRATION a. Think: considering what we have learned in this chapter, what do you see in this reaction? b. C6H12O6 + 6O2 6CO2+ 6H2O + ENERGY