Chapter 6- An Introduction to Metabolism* *Lecture notes are to be used as a study guide only and do not represent the comprehensive information you will need to know for the exams. The Energy of Life The cell can be viewed as a chemical factory it can convert sugars to amino acids, and vice versa; it can make polymers and convert them to monomers, and vice versa. Metabolism is involved in these processes, there is a flow of energy (Figure 6.1). Concept 6.1: An organism s metabolism transforms matter and energy Metabolism is the sum total of the cell s biochemical reactions. Metabolic Pathways A metabolic pathway begins with a specific molecule, which is then converted through a series of steps by the activity of enzymes that then produce products (Diagram pg. 122). Metabolism is broken down into two (2) types of pathways: 1) catabolic pathways break down a molecule in a process called degradative, and releases energy. An example is cellular respiration; 2) anabolic pathways builds molecules and consumes energy to do this in a process called biosynthetic pathways. An example is protein translation. Energy is fundamental to all metabolic processes. Bioenergetics is the study of how energy flows through living organisms. Forms of Energy Energy is the capacity to cause change, to do work. There are different types of energy. Kinetic energy is the energy displayed by moving objects. Heat, or thermal energy is kinetic energy associated with the random movement of atoms or molecules. An object that exists at a particular location in space is called potential energy. Chemical energy (as used in biology) is potential energy that is stored in the chemical bonds of a molecule, such as glucose. Figure 6.2 diagrams the relationship between potential energy and kinetic energy. 1
The Laws of Energy Transformation Thermodynamics is the study of energy transformations. In the study of thermodynamics, the object (matter) under study is called the system, everything else outside the system is called the surroundings. An isolated system (also known as a closed system) does not exchange energy with its surroundings. Conversely, an open system can exchange energy and matter with its surroundings. Organisms are open systems. Two (2) laws of thermodynamics govern energy transformations in organisms. The First Law of Thermodynamics The first law of thermodynamics states that energy is neither created nor destroyed. Energy is just converted from one form to another (Figure 6.3a). The Second Law of Thermodynamics During energy transformations, some energy is lost as heat (Figure 6.3b). When usable energy is lost, as a result, disorder can be created. Entropy is a measure of disorder, or randomness. The second law of thermodynamics states that systems tend towards disorder. A process that can occur without the input of energy is called a spontaneous process, meaning that the process is energetically favorable. Biological Order and Disorder Cells create ordered structures from less organized starting materials (Figure 6.4). Concept 6.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously In Biology we want to know which biochemical reactions occur spontaneously, and which ones require an input of energy from outside. Free-Energy Change, G Gibb s free energy of a system is symbolized by the letter G. 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. 2
The change in free energy, G, can be calculated for a chemical reaction: G = H T S. Once we know the value of G, we can determine if the reaction is energetically favorable, spontaneous. Processes that produce a negative G, ( G <0), are spontaneous, they decrease the free energy. Processes that have a positive G ( G>0), or 0, are never spontaneous. The values indicated which reactions can change without help. Spontaneous changes can be harnessed to perform work. Free Energy, Stability and Equilibrium G can be negative only when the process involves a loss of free energy. Free energy is a measure of a system s instability its tendency to change to a more stable state. Systems tend to move towards greater stability (Figure 6.5). Equilibrium as it relates to chemical equilibrium is when the forward reaction and the reverse reaction occur at the same rate. As the reaction proceeds to equilibrium the free energy of the reactants and products decreases. When the system is at equilibrium G is at its lowest possible value in that system. A process is spontaneous and can perform work only when it is moving towards equilibrium. Free Energy and Metabolism The concept of free energy and how it applies to life. Exergonic and Endergonic Reactions in Metabolism An exergonic reaction (energy outward) proceeds with a net release of free energy (Figure 6.6a). G is negative, therefore the reaction can occur spontaneously. An endergonic reaction (energy inward) absorbs energy from its surroundings (Figure 6.6b). G is positive, therefore the reaction is non-spontaneous. Equilibrium and Metabolism Metabolism in a cell never reaches equilibrium. Energy and matter continuously flow in and out of a cell, an open system. Cells carry out cellular respiration that releases energy. Some of the reactions of cellular respiration are pulled in one direction, therefore never reaching equilibrium (Figure 6.7). Concept 6.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions 3
A cell does three kinds of work: 1) chemical work the synthesis of making polymers from monomers; 2) transport work moving molecules across the cell membrane; 3) mechanical work used for cellular movement. Cells use energy coupling to accomplish these processes linking an exergonic reaction to an endergonic one. ATP is one of the main sources of energy to allow this to happen. The Structure and Hydrolysis of ATP ATP (adenosine triphosphate) has the phosphate functional group, it is used to store energy, and it is a nucleotide in DNA (Figure 6.8). ATP is hydrolyzed by a water molecule with the result being the cleaving of the phosphate bond, from the terminal phosphate end. The reaction is exergonic and releases energy. How the Hydrolysis of ATP Performs Work The use of specific enzymes in the cell is able to use the energy released by ATP hydrolysis directly to drive chemical reactions in the cell. Endergonic reactions in the cell are coupled to ATP hydrolysis, thus the reaction can proceed from reactants to product, such that the overall reaction in exergonic (Figure 6.9). During this process a phosphate group is transferred to one of the reactants creating a phosphorylated intermediate. Transport and mechanical work in the cell are accomplished by the hydrolysis of ATP (Figure 6.10 a and b). The Regeneration of ATP ATP is regenerated from ADP by an addition of a PO4 function group to form ATP. This is a continuous process called the ATP cycle (Figure 6.11). Concept 6.4: Enzymes speed up metabolic reactions by lowering energy barriers The laws of thermodynamics will tell us if a reaction is spontaneous, but it does not tell us the rate of the reaction, meaning, how fast the reaction will occur. An enzyme is a macromolecule (in this case a protein) that 4
acts as a catalyst, a chemical agent that speeds up a chemical reaction without being consumed by the reaction. The Activation Energy Barrier The initial energy that is needed to start a chemical reaction is called the activation energy, EA. Activation energy is often supplied in the form of heat. When the molecules have absorbed enough energy to break its bonds, the reactants move to a transition state (Figure 6.12). When the atoms move to the downhill part of the curve, energy is released, thus an exergonic reaction. The activation energy provides a barrier that determines the rate of the reaction. How Enzymes Lower the EA Barrier Organisms use catalysts to speed up reactions in the cell, and not heat. An enzyme catalyzes a reaction by lowering the EA barrier (Figure 6.13). An enzyme does not change the G, it just speeds up the rate of the reaction, how fast it will occur. Enzymes are specific for the chemical reactions they catalyze. Substrate Specificity of Enzymes The reactant for the enzyme is called the substrate. Once the enzyme binds to the substrate, it forms an enzyme-substrate complex (See equation pg. 132). Most names for enzymes end in ase. Enzymes are very specific for the substrate they bind. The active site is a pocket, or groove, on the surface of the enzyme where the substrate binds. It is the site for the catalysis (Figure 6.14a). When the substrate binds to the active site, there is an induced fit of the substrate in the active site (Figure 6.14b). Catalysis in the Enzyme s Active Site The catalytic cycle of the enzyme is its ability to convert substrate to product very rapidly (Figure 6.15). An enzyme can catalyze either the forward and reverse reaction, depending on which direction has the negative G. There are four mechanisms of catalysis: 1) the active site provides a place for substrates to come together in the proper orientation for the reaction to occur; 2) the enzyme can stretch the substrate towards the transition state; 3) the active site can provide a micro-environment that is optimal for catalysis to occur; 4) sometimes the amino acids in the active directly participate in the conversion to product. The enzyme can become saturated with the substrate such that there is always a turn over of substrate to product. 5
Effects of Local Conditions on Enzyme Activity The activity of an enzyme is influenced by temperature, ph and different types of chemicals. Effects of Temperature and ph Proteins are sensitive to their environment. The optimal conditions favor the active shape for the enzyme. An above normal temperature for the enzyme can destroy the shape of the enzyme by disturbing the ionic, hydrogen and van der Waals interactions causing the enzyme to denature (Figure 6.16a). Enzymes also have an optimal ph for which they can function (Figure 6.16b). Cofactors Cofactors are nonprotein helpers for the enzyme. Cofactors for some enzymes are inorganic, such as metal ions, like zinc and magnesium. If the cofactor is an organic molecule, it is called a coenzyme, which tend to be vitamin derivatives. Enzyme Inhibitors They inhibit the activity of the enzyme. Competitive inhibitors prevent the natural substrate from binding to the active site (Figure 6.17 a and b). Non-competitive inhibitors do not bind directly in the enzyme s active site, but on another portion of the enzyme. Once this non-competitive inhibitor binds, it changes the shape of the active site so that the natural substrate does not bind (Figure 6.17c). The Evolution of Enzymes Mutations of a gene that codes for an enzyme may have given rise to different enzymes with novel functions. Natural selection would favor the gene of a particular enzyme for an organism s habitat. Concept 6.5: Regulation of enzyme activity helps control metabolism The cell can control when and where its enzymes are active. The cell can control the genetic production of enzymes, or regulate their activity once they are made. 6
Allosteric Regulation of Enzymes They function similarly to non-competitive inhibitors. They affect the shape and functioning of the active site by binding elsewhere on the enzyme. Allosteric regulation describes where a protein s function at one site is affected by the binding of a regulatory molecule to a separate site. It can either inhibit or stimulate the enzyme s activity. Allosteric Activation and Inhibition Enzymes that are regulated by this mechanism tend to contain multiple subunits, and the overall enzyme oscillates between an active and inactive shape (Figure 6.18a). An activator will allow the enzyme to function. An inhibitor will prevent the enzyme from functioning. Cooperativity occurs when a substrate binds to a multisubunit enzyme, and once the first substrate binds it allows for the other same substrate to bind to the enzyme easier (Figure 6.18b). Feedback Inhibition The metabolic end product of a pathway inhibits one of the first enzymes in the pathway (Figure 6.19). Organization of Enzymes Within the Cell The eukaryotic cell is compartmentalized. Some enzymes and enzyme complexes have fixed locations within the cell (Figure 6.20). 7