Energy and Metabolism1 Energy and Metabolism Chapter 6 Topics you are not responsible for: How biochemical pathways evolve Read on your own about: Laws of thermodynamics End of Chapter questions: all Do all mQuiz questions

Energy and Metabolism2 How does the body “deal with” alcohol? Too much of a bad thing  Too much of a good thing NADH -- e- source for ATP production -- too much causes metabolic disorders ADH deficiency in Asian races Disulfiram (antabuse) – ADH inhibitor

Energy and Metabolism3 How much “useable” energy exists in the molecules of a cell? G = H - TS G = usable energy (Gibbs free energy) Which equals … H = energy content in the molecular bonds (enthalpy)? … Less … S = disorder (entropy) x T emperature (Kelvin scale)

Energy and Metabolism4 What happens to the energy of a molecule during a chemical reaction? How does the energy content in the molecular bonds (enthalpy) change? Δ H How does the energy of disorder (entropy) change? ΔS (x T emperature) How does the total usable (‘Free’) energy (G) of the system change during the reaction? ΔG = ΔH – ΔST = -7 Kcal/mol “Catabolic” reaction “Exergonic” -- energy is released

Energy and Metabolism5 Catabolic (exergonic) reactions occur spontaneously… but often slowly. Why? What is activation energy?

Energy and Metabolism6 What happens if the reaction is reversed? Will ΔG (usable energy of the system) be increase or decrease? What happens to useable energy of the system? ΔG = ΔH – ΔST = +7 Kcal/mol Example of an Anabolic reaction (endergonic) -- energy must be added to the system

Energy and Metabolism7 How does an enzyme affect reaction energetics? How does it do so? “Catalytic site” Substrate orientation Enzyme movements Bond destabilization Catalysis Funke T et al. PNAS 2006;103: EPSP synthase binding to SP3

Energy and Metabolism8 Enzyme reactions are reversible In a closed system will reach “equilibrium” -- what does this mean? Sucrase Equilibrium Constant = 1.4x10 5 (140,000) = [products] = ____[G] x [F]___ [reactants] [sucrose] x [H 2 0] If > 1, Rx is exergonic Why aren’t [ ]s the same at equilibrium? -- affinities for catalytic site What is EC of reverse sucrase reaction?

Energy and Metabolism9 In enzymatic reactions, energy can pass to or from ATP Glutamine synthase reaction Glutamate + NH 3 + ATP  Glutamine + ADP + Pi if: Substrate +ATP  Product + ADP +Pi = endergonic / anabolic reaction if: Substrate +ADP+Pi  Product + ATP = exogonic / catabolic reaction Understand this

Energy and Metabolism10 What is a metabolic pathway? -- sequential series of enzymatic reactions -- e.g., Glycolysis, Krebs cycle, etc. Enzyme 1 Enzyme 2 Enzyme 3 Cellular “metabolism” = sum of all enzymatic activities

Energy and Metabolism11 If all enzymes are reversible, then why do molecules pass one way through metabolic pathways? What controls flow direction? 1) Reactant vs Product affinities 2) Reactant vs Product concentrations 2) Product removal Fig 6.13 in text is special case

Energy and Metabolism12 What controls the rate of enzyme activity? Various physical factors? pH Temperature Reactant & substrate concentrations Activators and Inhibitors Models

Energy and Metabolism13 Control of enzyme activity, con’t. Inhibitors competitive vs non-competitive Inhibitors Non-competitive = “allosteric regulation”

What is feedback inhibition? Common regulatory mechanism Response to decreased demand for products

Energy and Metabolism15 In oxidation/reduction reactions, what serve as electron carrier? Substrate + NAD  Product + NADH = substrate oxidation Substrate + NADH  Product + NAD = substrate reduction Understand this NADH, FADH, NADPH examples of “coenzymes” Lactate dehydrogenase Rx