Overview of Thermodynamics and Metabolism Biochem 4511 Figures Essential Biochemistry 3rd Ed Pratt and Cornely Principles of Biochemistry 5th Ed Moran et al Lehninger Principles of Biochemistry 5th Ed Nelson Cox Fundamentals of Biochemistry 2nd Ed Voet Voet Pratt Thermodynamic Overview What is enthalpy How does it relate to endothermic and exothermic reactions What is entropy What is Gibb s free energy How do you use Gibb s free energy to predict if a reaction will occur Know the basic equations relating G H and S to each other and to equilibrium constants Understand the importance and provide examples of coupled reactions Thermodynamics Derived from Ancient Greek Therme Heat Dynamis Power Thermodynamics is the set of rules that describe how energy and matter behave at a macroscopic level Predicts macroscopic properties including whether or not a chemical reaction will occur Does NOT describe how quickly the reaction will occur kinetics State Function A D Reactants Products The relationship of reactants to products in a chemical reaction is independent of the mechanism by which you interconvert them A y g r e n E D D A y g r e n E Rxn coordinate Rxn coordinate Enthalpy H a Very Useful State Function H between initial and final stages of a reaction is the heat that a reaction generates or absorbs Since enthalpy is a state function we can take any path from reactants to products and enthalpy will be the same Consider the breakdown of glucose to CO2 and H2O CO2 H2O You can measure the energy produced by this reaction by combustion in a calorimeter Or you can complete this reaction biochemically Glucose Metabolism The energy generated is the same for either pathway Entropy Entropy S is a measure of disorder Remember the universe tends to disorder Entropy is also a state function Entropy of a Molecule Entropy of a molecule is the sum of Translational entropy motion Rotational entropy motion Internal entropy vibrational internal rotation Translational and rotational entropy are proportional to the number of molecules this is the primary cost when 2 molecules condense to form 1 molecule Remember the hydrophobic effect the entropy of the protein 1 molecule is reduced but the entropy of the system many water molecules is significantly increased Entropy and Temperature Systems become more disordered as the temperature of the system increases Entropy and Enthalpy Biological processes are a balance of entropy and enthalpy Entropic forces Two strands of DNA are associated as one unit The DNA strands are formed into the more rigid double helix instead of randomly moving about in solution Order and disorder of water Enthalpic forces Base stacking stacking Hydrogen bonding Shape complementarity Electrostatic interactions will occur take place Reaction Spontaneity Enthalpy is insufficient to determine whether a reaction o Endothermic requires heat reactions take place Entropy is insufficient to determine whether a reaction will Water 2 H2O does not convert spontaneously to hydrogen and oxygen 2H2 O2 We need some new parameter to define spontaneity Gibbs Free Energy G considers both the enthalpy and entropy of a chemical reaction G H T S Determining Spontaneity Exergonic G 0 spontaneous Endergonic G 0 not spontaneous The reverse reaction is spontaneous Equilibrium G 0 no net reaction occurs Exergonic G 0 spontaneous Endergonic G 0 not spontaneous The reverse reaction is spontaneous Equilibrium G 0 no net reaction occurs Standard Conditions In order to compare the energy of a variety of reactions it is necessary to define a set of standard conditions Go is the free energy change under standard conditions Standard Conditions In Chemistry P 1atm ALL 1 M T 298oK 25oC In Biochemistry the same AND Water 55 5M H 10 7M pH 7 0 However in real life and physiological conditions components are rarely at 1M concentrations Thermodynamic Equilibria Go RT lnKeq At equilibrium DG 0 For any reaction Go may be calculated from the equilibrium constant Keq when R is the gas constant 8 3145 J K mol and T is the reaction temperature in Kelvin Keq e G RT Keq C eqD eqA eqB eq Thermodynamic Equilibria Go RT lnKeq Keq e DG RT The Go of a typical H bond 21 kJ mol Coupled Reactions Equations A B C D D E F G A B D E C D F G A B E C F G Discrete reactions may be coupled through a common intermediate compound D in this example Coupling reactions is the basis for metabolic pathways and links different pathways together Coupled Reactions An unfavorable reaction A B may be coupled to a favorable reaction B C As long as the overall G is 0 the overall reaction A C will be spontaneous This is concept is VERY important in metabolism Coupled Reactions and ATP ATP is the primary energy currency of cells Cleavage of the phosphoanhydride bond is highly favorable exergonic We will discuss this in more detail soon ATP hydrolysis can be coupled to endergonic reactions to drive a pathway ATP Hydrolysis Drives Glucose Phosphorylation Glucose entering an intestinal cell is phosphorylated to glucose 6 phosphate endergonic to trap the molecule within the cell This is also the first step of glycolysis Coupling this reaction with ATP hydrolysis exergonic yields a spontaneous reaction The Go values for each reaction are added to give the total Go value for the coupled reaction 16 7 kJ mol The net reaction has a negative Go so the reaction is spontaneous Coupled Reactions and ATP Coupled Reactions and Enzymes First reaction Highly Exergonic Second reaction Endergonic Metabolism Overview Chapter 12 Biochem 4511 Figures Essential Biochemistry 3rd Ed Pratt and Cornely Principles of Biochemistry 5th Ed Moran et al Lehninger Principles of Biochemistry 5th Ed Nelson Cox Biochemistry 3rd Ed Voet Voet Fundamentals of Biochemistry 2nd Ed Voet Voet Pratt Overview of Metabolism Breaking down molecules Building up molecules Anabolic reactions are the assembly of smaller molecules to form macromolecules and typically require energy Free energy often provided by the hydrolysis of ATP Catabolic reactions are the breakdown of larger molecules macromolecules and are typically exergonic Free energy released can be used to generate ATP or other energy storage molecules The human diet primarily consists of four different classes of macromolecules which are broken down into their monomeric components through digestion Proteins Amino Acids Nucleic acids Nucleotides Polysaccharides Monosaccharides Fats particularly triacylglycerols Fatty Acids Required metals ions and