CHAPTER 8 METABOLISM 1 The sum total of

CHAPTER 8 - METABOLISM 1

� � � The sum total of an organism’s chemical reactions is called metabolism. The chemistry of life is organized into metabolic pathways. A metabolic pathway begins with a specific molecule, which is then altered in a series of defined steps to form a specific product. A specific enzyme catalyzes each step of the pathway. Remember, enzymes are not changed or used up during the reaction they are catalyzing. Metabolism 2

Catabolic Pathways = Breaking down molecules; Releases Energy; Utilizes Hydrolysis; Ex. Cellular Respiration (breaking down sugars to get ATP) Anabolic Pathways = Building up molecules; Stores Energy (in bonds); Utilizes Condensation or Dehydration Synthesis; Ex. Protein Synthesis (from amino acids) Building Molecules – Anabolic Pathways Breaking Down Molecules – Catabolic Pathways 3

Energy � � Bioenergetics is the study of how energy flows through living organisms. Organisms transform energy can be converted from one form to another. Energy is the capacity to cause change. � Kinetic energy is the energy associated with the relative motion of objects. Thermal energy is kinetic energy associated with the random movement of atoms or molecules. � Potential energy is the energy that matter possesses because of its location or structure. Chemical energy is a term used by biologists to refer to the potential energy available for release in a chemical reaction; stored in bonds 4

Hydroelectric Systems Open vs. Closed Thermodynamics is the study of energy transformations that occur in a collection of matter. - An isolated system (or CLOSED system), is unable to exchange either 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 In a closed system, eventually it reaches equilibrium and no more work can be done. If no work can be done, the organism would eventually die. The key to keeping disequilibrium is for the product of one step to be the reactant of the next (open systems) 5

� � Two laws of thermodynamics govern energy transformations in organisms and all other collections of matter. The first law of thermodynamics states that the energy of the universe is constant: Energy can be transferred and transformed, but it cannot be created or destroyed. (“conservation of energy”) First Law of Thermodynamics 6

Second Law of Thermodynamics � � � Entropy (∆S) is a measure of disorder or randomness; the more random a collection of matter, the greater its entropy. The second law of thermodynamics states: Every energy transfer or transformation increases the entropy of the universe. Every reaction increase the entropy of the UNIVERSE, even if it decreases the entropy in that exact system. Much of the increased entropy of the universe takes the form of INCREASING HEAT, which is the energy of random molecular motion. 7

Spontaneous vs. Non-Spontaneous Processes Spontaneous = always going to a more stable position (increasing entropy); decreasing Free Energy (∆G); can occur WITHOUT the input of energy Non-Spontaneous = going to a less stable position (decreasing entropy); increasing Free Energy (∆G ); needs energy input to occur Unstable = ↑ Free E Stable = ↓ Free E 8

Free Energy � � � Free energy is the portion of a system’s energy that can perform work when temperature and pressure are uniform throughout the system, as in a living cell. The change in free energy, ∆G, can be calculated for any specific chemical reaction by applying the following equation: ∆G = ∆H – T∆S In this equation, ∆H symbolizes the change in the system’s enthalpy (in biological systems, equivalent to total energy or HEAT); ∆S is the change in the system’s entropy; and T is the absolute temperature in Kelvin (K) units (K = °C + 273). ∆G is negative when the process involves a LOSS of free energy during the change from initial state to final state; because it has less free energy, the system in its final state is less likely to change and is therefore more stable (+∆S) than it was previously. ∆G is positive when the process involves a GAIN of free energy; the result is usually less stable (-∆S) than what you started with A system at equilibrium is at maximum stability. However, at equilibrium, G = 0, and the system can do no work (so a cell would die). 9

Endergonic vs. Exergonic Reactions Exergonic → releasing energy; reactants have MORE energy than products; ∆G = negative Endergonic → absorbing energy from environment; reactants have LESS energy than products; ∆G = positive 10

Energy Profile – Exergonic Reaction Reactants AB and CD must absorb enough energy from the environment to become unstable enough to overcome the activation energy (EA) and reach the transition state. Bonds then break, and new bonds form. In the process, energy is released to the surroundings. Exergonic = Products have LESS free energy than Reactants (because some of it got lost to the environment). 11

Spontaneous Catabolic (breaking down) Exergonic (giving off E) Breaking Down Breaking Bonds (HYDROLYSIS) Release Free Energy ∆G = Negative (Free energy decreases) ∆ S = Positive (disorder (entropy) increases) Stability Increases Non-Spontaneous Anabolic (building up) Endergonic (absorbing E) Building up Making Bonds (DEHYDRATION) Storing Free Energy ∆G= Positive (free energy increases) ∆S = Negative (disorder (entropy) decreases) Stability Decreases 12

� A cell does three main kinds of work: Chemical work, such as the synthesis of polymers from monomers; � Transport work, pumping substances across membranes; � Mechanical work, such as the beating of cilia, contraction of muscle cells, and movement of chromosomes during cellular reproduction; � � Cellular Work and Energy Coupling Cells manage their energy resources to do this work by energy coupling, using an exergonic process to drive an endergonic one. 13

ATP To break down ATP, break off the 3 rd phosphate; this releases about +7. 3 kcal/mol of energy Adenosine triphosphate (ATP!) is the energy molecule for cells. It is composed of the sugar ribose, the nitrogen base adenine, and three phosphate groups. The third phosphate can be broken off and transferred to another molecule to transfer the energy. The ATP is turned into ADP in that process. In the cell, the energy from the hydrolysis of ATP is directly coupled to endergonic processes by the transfer of the phosphate group to another molecule. This new phosphorylated molecule now has more energy since it got the phosphate group. 14

ATP loses a phosphate to form ADP, energy, and an inorganic phosphate. A working muscle cell recycles its entire pool of ATP once each minute. More than 10 million ATP molecules are consumed and regenerated per second per cell. 15

ATP Cycle Transferring of a phosphate can transfer energy from one molecule to another. 16

Enzymes Lower Activation Energy (EA) 17

Enzymes and Activation Energy � � � An enzyme is a protein that acts as a catalyst; which is a molecule that speeds up a chemical reaction WITHOUT being changed or consumed during the reaction. Activation Energy (EA) the energy needed for a reaction to occur � Sometimes just thermal energy at room temperature is enough to get the reactants to reach the transition state Enzymes work by LOWERING the amount of activation energy required for a reaction to occur (they do NOT give energy to the reaction) 18

� In most cases, EA is high enough that the transition state is rarely reached and the reaction hardly proceeds at all. In these cases, the reaction will occur at a noticeable rate only if the reactants are heated. � Heat would speed up all reactions, not just those that are needed. � Heat also denatures proteins and kills cells. Activation Energy 19

Enzyme Substrate Complex The reactant that an enzyme acts on is the substrate. The enzyme binds to a substrate, or substrates, forming an enzymesubstrate complex. The reaction catalyzed by each enzyme is very specific. The active site of an enzyme is typically a pocket or groove on the surface of the protein where catalysis occurs; the spot where the enzyme reacts with the substrate. Notice: In this process we are breaking apart sucrose, so we are putting water in to break the bond – HYDROLYSIS! The specificity of an enzyme is due to the fit between the active site and the substrate. 20

Induced Fit Theory The Induced Fit Theory says that when the substrate binds with the enzyme at the active site, the enzyme may change shape slightly to have more of a “snug” fit. . This shape change brings the chemical groups of the active site into position to catalyze the reaction. 21

� � � The R groups of a few amino acids on the active site catalyze the conversion of substrate to product. Enzymes are unaffected by the reaction and are reusable. Most metabolic enzymes can catalyze a reaction in both the forward and reverse directions; in the direction of equilibrium. The rate at which a specific number of enzymes convert substrates to products depends in part on substrate concentrations; however, there is a limit to how fast a reaction can occur. At high substrate concentrations, the active sites on all enzymes are engaged. � The enzyme is saturated, and the rate of the reaction is determined by the speed at which the active site can convert substrate to product. � The only way to increase productivity at this point is to add more enzyme molecules. 22

Enzyme activity is affected by environmental factors Each enzyme works best at certain optimal conditions. Temperature p. H Temperature has a major impact on reaction rate. Higher temp = more collisions = more reactions…just need to be careful of DENATURATION! Most human enzymes have optimal temperatures of about 35– 40°C. Each enzyme also has an optimal p. H. This optimal p. H falls between 6– 8 for most enzymes. However, digestive enzymes in the stomach are designed to work best at p. H 2, whereas those in the intestine have an optimal p. H of 8. 23

Cofactors � � Many enzymes require non-protein helpers, called cofactors, (usually minerals) to be activated. Organic cofactors are called coenzymes (usually vitamins. ) 24

Competitive vs. Non-Competitive Inhibition Enzymes can be inhibited either competitively or non-competitively: Competitive Inhibition = an inhibitor mimics the shape of the substrate and gets in the way of the active site of the enzyme; so it is competing for the active site; ADDING SUBSTRATE would overcome competitive inhibition Non-Competitive Inhibition = an inhibitor binds to an allosteric site (a site on the enzyme that is NOT the active site) and therefore changes the shape of the active site on the enzyme. This prohibits the substrate from properly connecting with the enzyme and renders it useless. It is NOT competing for the active site because it uses an allosteric one. 25

Allosteric Regulation An allosteric site is a spot on an enzyme away from the active site where an inhibitor OR activator can bind affect the function of that enzyme. The binding of an activator stabilizes the conformation that has functional active sites, whereas the binding of an inhibitor stabilizes the inactive form of the enzyme 26

Another Picture on Allosteric Regulation… 27

Cooperativity When an enzyme is made up of different subunits, the binding of a substrate in the active site of ONE of the subunits can force the other subunits to stay in the active conformation. This is called cooperativity. This amplifies the response of enzymes to substrates, priming the enzyme to accept additional substrates. 28

Feedback Inhibition = The switching OFF of a metabolic pathway by one of its end products. The end product acts as an inhibitor of one of the enzymes in the pathway (usually allosterically). The process helps cells regulate and not waste any resources by making TOO MUCH of a certain product. 29

Location of Enzymes in a Cell helps Organize Metabolism � � The cell is compartmentalized: The organization of cellular structures including organelles and membranes helps bring order to metabolic pathways. Having the enzymes needed for a specific process all in the same place helps make the process more efficient. For example, all the enzymes needed for photosynthesis are found in the chloroplast. 30