9/2/13 1 Chapter 3 Energy, Catalysis and Biosynthesis Be Able To • Describe the 1st and 2nd laws of thermodynamics. • Define ΔG, ΔGO and Keq, and know the relationship between the terms. Know the equations to calculate each of them given a reaction and the concentration of reactants and products. • Predict whether a reaction will occur spontaneously based on the values of ΔG. Why are coupled reactions important to biology? • Compare oxidation and reduction reactions. Which form of carbon yields the most amount of energy? • Explain why enzymes are used in biological systems. How do they increase the rate of a reaction? Do they change the equilibrium of a reaction? • Compare competitive and non-competitive inhibition in terms of Vmax and KM. Be able to draw the results from an enzyme assay for each.9/2/13 2 Basic Thermodynamics • First Law of Thermodynamics: Energy cannot by created or destroyed, but it can be converted from one form to another • Second Law of Thermodynamics: Energy spontaneously tends to disperse See http://secondlaw.oxy.edu/ for an excellent review of the Second Law and entropy!The Second Law states that ENTROPY increases whenever anything happens. The text defines entropy as disorder, but more accurately, it is the dispersal of energy. But cells are complex and highly organized. How do cells manage to create and maintain order despite ever increasing entropy?9/2/13 3 Cells use a tremendous amount of energy to create and maintain order. The Second Law still holds true because entropy in the surroundings increases, largely due to the release of heat (also energy!) Free Energy, G Panel 3-19/2/13 4 What determines whether a chemical reaction can occur? Change in free energy => ΔG Energetically favorable reactions have a negative ΔG ΔG = ΔH – TΔS Review Panel 3-1 Chemical reactions within the cell are reversible so ΔG depends on the energy stored in chemical bonds (ΔG°) and also on the concentration of the molecules in a reaction. "ΔG = ΔG° + RT ln [products]/[reactants] ΔG°, the standard free energy, reflects the intrinsic energy stored in bonds and is defined under standard conditions: • 25°C (298°K) • 1 atm pressure • All reactants and products at 1 M concentration • pH 79/2/13 5 ATP → ADP + Pi -7.3 kcal/mole glucose + fructose → sucrose +5.5 kcal/mole ΔG° Energetically favorable reactions have a negative ΔG Effect of concentrations on ΔG Example: glyceraldehyde 3-P (G3P) ⇔ dihydroxyacetone-P (DHAP) ΔG° = -1.8 kcal/mol ΔG = ΔG° + RT ln [products]/[reactants] ""ΔG = ΔG° + RT ln [DHAP]/[G3P], so "ΔG = -1.8 kcal/mol + 0.616 ln [DHAP]/[G3P] If [G3P] = 0.001 M and [DHAP] = 0.1 M : "ΔG = -1.8 kcal/mol + 0.616 ln [0.1]/[0.001] "ΔG = -1.8 kcal/mol + 2.8 kcal/mol = +1.0 kcal/mol the “favored” direction of the reaction is reversed!9/2/13 6 At equilibrium the forward and reverse RATES for a reaction are equal, but not necessarily the concentrations of the reactants and products. There is no work at equilibrium so ΔG = 0 0 = ΔG = ΔG° + RT ln Keq The effect of concentration is just sufficient to balance ΔG°. ΔG"at"Equilibrium"0 = ΔG = ΔG° + RT ln Keq ΔG°= -RT ln Keq = -0.616 ln Keq The greater the value for Keq, the more negative ΔG° ΔG° and Keq values can be used to predict: 1. Ratio of reactants to products at equilibrium 2. Direction of reactions Rela/onship"between"ΔG°"and"Keq"9/2/13 7 The ratio of reactants to products at steady state can be determined from ΔG° See Panel 3-1 has$a$ΔG°$=$&1.74$kcal/mol.$$Therefore,$its$equilibrium$constant$is:$"ΔG° = -RT lnKeq Keq = e(1.74/0.616) = 17 So the reaction will be at equilibrium when: [glucose-6-P]/[glucose-1-P] = 17 R + L ⇔ RL Keq = [RL] [R][L] Specificity"–"Nico/ne"for"Receptor"L = nicotine R = neuronal receptor R = muscle receptor Keq(N) = 1 x 106 Keq(M) = 2.5 x 103 Keq(N) / Keq(M) = 400 Specificity:9/2/13 8 03_18_Reaction coupling.jpg!Coupled reactions9/2/13 9 03_22_chemical siphon.jpg!Coupled reactions - Sequential “siphon” Coupled reactions - Activated carrier9/2/13 10 Biosynthesis and activated carrier molecules Activated carriers store energy in the form of a transferable chemical group or as high-energy electrons. ATP NADH and NADPH ATP is the most widely used activated carrier9/2/13 11 Phosphorylation is often the first step in condensation reactions Coupling to ATP hydrolysis Consider a generalized condensation reaction A-H + B-OH → AB + H2O This reaction is energetically unfavorable Coupling to ATP hydrolysis occurs in two steps 1. B-OH + ATP → B-O-PO3 + ADP 2. A-H + B-O-PO3 → AB + Pi + H2O Net reaction: B-OH + ATP + A-H → AB + ADP + Pi Note: B-O-PO3 is a phosphorylated intermediate What are the biological constraints?9/2/13 12 NAD+ and NADP+ are electron carriers that facilitate oxidations and reductions A + e- + H+ → AH Environment • Light (electromagnetic energy) • Food (chemical bond energy) Where do cells get the energy required to create and maintain order? Conversion of energy - First Law of Thermodynamics9/2/13 13 Cells obtain energy from the oxidation of organic molecules (partial harvest of bond energies) Glucose + 6O2 → 6CO2 + 6H2O In the presence of oxygen: The most energetically stable form of C is CO2 The most energetically stable form of H is H2O9/2/13 14 Review: Oxidations and Reductions Generally applies to the gain or loss of electrons • Loss of electron = oxidation • Gain of electron = reduction Electron transfer often also involves a proton A + e- + H+ → AH Hydrogenation = reduction Dehydrogenation = oxidation Reduced organic compounds yield more energy (electrons) for chemical work: fats > sugars9/2/13 15 Spontaneous Reactions Glucose + 6O2 → 6CO2 + 6H2O ΔG= -686 kcal/mole This oxidation reaction has a very large, negative ΔG. Therefore, according to the Second Law, it can proceed “spontaneously.” Does this happen? A large amount energy is dispersed during this oxidation. If simply burnt, the energy is lost as heat. Glucose + 6O2 → 6CO2 + 6H2O ΔG= -686 kcal/mole Cells carry out this process in many steps to harness some of the energy for chemical work Enzymes9/2/13 16 Activation energy Even energetically favorable reactions need a boost Enzymes supply the boost (what about heat?) Enzymes (usually proteins) increase the rate of