9 - Metabolic Control Analysis & Introduction to...

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Unformatted text preview: Metabolic Control Analysis & Introduction to Metabolomics BCH 3120 Feb 7, 2011 A B C Where are the control points for pathway flux? How important are each of these points? How do we know? Midterm I Marks The average mark for MCQ and T/F questions is 82% Well done! (better than previous 5 years!) The b Fill-in-the-blank ` section is now being marked, and collated with marks from MCQ and T/F sections. l Marks should be accessible individually to you on Virtual Campus-Blackboard late Wednesday. Lecture Outline Why is control necessary? Basic principles of thermodynamics l Laws of Thermodynamics l Entropy, Enthalpy l K eq l Gibbs Free Energy: Standard and Actual Traditional Methods of Identifying Pathway Control Steps Metabolic Control Analysis Metabolomics An Introduction Why is Control Necessary? 1. To provide products at a rate that they are needed (i.e., to balance supply with demand) 2. To maintain the steady-state concentrations of the intermediates in a pathway within a narrow range ( i.e., homeostasis) Thermodynamics The committing step catalyses a reaction that has a large free energy change (irreversible step) The other enzyme reactions are characterized by a relatively lower free energy change q Cellular compartmentalisation q Thermodynamics q Inhibition and allostery q Post-translational modifications q Enzyme turnover A B C D 1 2 3 A B C D 3rd enzyme reaction Committing/ Controlling step (1) 2 nd enzyme reaction Flux Free Energy ( G) Thermodynamics and Control of Metabolic Pathways The Laws of Thermodynamics First Law: The principle of the conservation of energy : for any physical or chemical change, the total amount of energy in the universe remains constant . l ( i.e., Energy can change form, or be transported, but cannot be created or destroyed .) Second Law: In all natural processes, the entropy of the universe increases . The second law is a fact of life : l Entropy happens z ! Important terms and definitions Gibbs free energy, G : l the amount of energy capable of doing work for a reaction at constant temperature and pressure. l Exergonic (- G) vs. endergonic (+ G). Implications? Enthalpy, H : l the heat of the reacting system, reflecting the number and types of chemical bonds in reactants and products. l Exothermic (- H) vs endothermic (+ H) Entropy, S : l a value indicative of the disorder within the system. l When reaction products are more complex than substrates, then S is negative (and vice versa) A b thermodynamic system ` can be a single chemical reaction, or an entire system The above three thermodynamic quantities are related by the equation: G = H (T S) l Where T is absolute temperature (in K) Describes a change in free energy during a chemical reaction Starting with concentrations of reactants and products= 1M; Temp= 298 K (25 o C); pH= 7, and atmospheric pressure= 1 atm ***It is directly related to the Equilibrium Constant (K...
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This note was uploaded on 12/18/2011 for the course BCH 3120 taught by Professor Mary-ellenharper during the Winter '11 term at University of Ottawa.

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9 - Metabolic Control Analysis & Introduction to...

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