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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. How does the body “deal with” alcohol?
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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 Metabolism
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 Metabolism
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 Temperature (Kelvin scale) Energy and Metabolism
What happens to the energy of a molecule during a chemical reaction? How does the energy content in the molecular bonds (enthalpy) change? ΔH How does the energy of disorder (entropy) change? ΔS (x Temperature) How does the total usable (‘Free’) energy (G) of the system change during the reaction? ΔG = ΔH– ΔST = -7 Kcal/mol “Catabolic”reaction “Exogonic” -- energy is released Energy and Metabolism
Catabolic (exogonic) reactions occur spontaneously… but often slowly. Why? What is activation energy? Energy and Metabolism
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 Metabolism
How does an enzyme affect reaction energetics? How does it do so? “Catalytic site” Substrate orientation Enzyme movements Bond destabilization EPSP synthase binding to SP3 Catalysis Funke T et al. PNAS 2006;103:13010-13015 Energy and Metabolism
Enzyme reactions are reversible In a closed system. . . . . . will reach “equilibrium” -- what does this mean? Sucrase Equilibrium Constant = 1.4x105 (140,000) = [products] = ____[G] x [F]___ [reactants] [sucrose] x [H20] If > 1, Rx is exogonic Why aren’t [ ]s the same at equilibrium? -- affinities for catalytic site What is EC of reverse sucrase reaction? Energy and Metabolism
In enzymatic reactions, energy can pass to or from ATP Glutamine synthase reaction Glutamate + NH3 + ATP Glutamine + ADP + Pi Understand this if: Substrate +ATP Product + ADP +Pi = endergonic / anabolic reaction if: Substrate +ADP+Pi Product + ATP = exogonic / catabolic reaction Energy and Metabolism
Enzyme 1 Enzyme 2 Enzyme 3 What is a metabolic pathway? -- sequential series of enzymatic reactions -- e.g., Glycolysis, Krebs cycle, etc. Cellular “metabolism” = sum of all enzymatic activities Energy and Metabolism
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 Metabolism
What controls the rate of enzyme activity? Various physical factors? pH Temperature Reactant & substrate concentrations Activators and Inhibitors Models Energy and Metabolism
Control of enzyme activity, con’t. Inhibitors competitive vs non-competitive Non-competitive = “allosteric regulation” Inhibitors Energy and Metabolism
What is feedback inhibition? Common regulatory mechanism Response to decreased demand for products
Understand this Substrate + NAD Product + NADH = substrate oxidation Substrate + NADH Product + NAD = substrate reduction In oxidation/reduction reactions, what serve as electron carrier? NADH, FADH, NADPH examples of “coenzymes” Lactate dehydrogenase Rx Energy and Metabolism