Ch11-120307 - CHEM 350 Introduction to Biological Chemistry...

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Unformatted text preview: CHEM 350: Introduction to Biological Chemistry Brian Lee, Ph.D. [email protected] Office: Neckers 146G or 324 Phone: 453-7186 Ho urs: 9:30am to 10:30am or by appointment Website: https:/ / Textbook (required, U.S. edition only) Fundamentals of Biochemistry, 3rd Ed., Voet, Voet & Pratt. Study Guide (recommended) Student Companion to Fundamentals of Biochemistry, 3rd Ed. Help Desk Tuesday 6:30 to 7:30 pm in Neckers 218 Thursday 5:00 to 6:00 pm in Neckers 410 Announcements Undergraduate Research Opportunities Research for credit (such as CHEM 396 or CHEM 496) Student worker ($8.00 per hour) ( Undergraduate Assistantships ( McNair Scholars Program ( REACH Awards Competition ( Summer Research Experiences for Undergraduates (REU) Deadline for SIUC REU Program is TODAY For other REU programs, search the National Science Foundation site: Students must contact the individual sites for information and application materials. NSF does not have application materials and does not select student participants. A contact person and contact information is listed for each site. Assignments Read Chapter 12 Enzyme Kinetics Chapter 12 Problems Student Companion site for Voet, Voet & Pratt Third Midterm Exam, Wednesday March 28th Chapters 10-13 Help Desk Tuesday 6:30 to 7:30 pm in Neckers 218 Thursday 5:00 to 6:00 pm in Neckers 410 Cofactors Enzymes may require cofactors for catalysis. A Cofactor is not consumed by the catalytic reaction. The Cofactor may be modified, but is always regenerated (sometimes by a secondary or accessory enzyme). Apoenzyme (inactive) + Cofactor = Holoenzyme (active) - Cofactors usually participate in catalysis and are often mo dified during the reaction. - Cofactors are returned to initial state before continuing catalysis. Cofactors: Metals Metal ions participate in the catalytic reaction. The multiple oxidation states of metal ions can be utilized in oxidationreduction reactions. Cofactors: Coenzymes Apoenzyme (inactive) + Cofactor = Holoenzyme (active) Coenzymes may be cosubstrates for the enzyme reaction. Tightly bound coenzymes are called prosthetic groups. Vitamins are often precursors to coenzymes. Vitamins related to disease and essential functions in cells thiamine B1 (beriberi neurodegenerative) required for carbohydrate metabolism – deficient in processed white rice riboflavin B2 required for electron transfer reactions niacin B3 (pellagra) common in rural South corn-rich diet, treating corn with lime, Ca(OH)2 (to make tortillas) allows niacin to be absorbed from corn pyridoxine B6 required for amino acid metabolism biotin B7 required for fatty acid metabolism cobalamin B12 (pernicious anemia) required for nucleotide and amino acid metabolism, directly involved in folate synthesis folic acid B9 (megaloblastic anemia during pregnancy) required for amino acid metabolism Coenzyme must be regenerated by another reaction, which may require another enzyme. (glyceraldehyde 3-phosphate oxidation in glycolysis by GAPDH) Thermodynamics Review Gibbs Free Energy • Biochemical standard free energy if G < 0, then spontaneous for a chemical reaction: A + B -> C + D [C][D] G = G° + RT ln [A][B] At equilibrium, G = 0 G°’ = -RT ln K’eq Under standard conditions K’eq = 10- G°’/5.7kJ/mol when Keq < 1 then G > 0 For example: DHAP -> GAP K’eq = GAP/DHAP = 0.0475 G°’ = -RT ln K’eq = 7.53 kJ/mol TIM: triose phosphate isomerase What if? [GAP] = 3 μM [DHAP] = 200 μM [GAP]/[DHAP] = 0.0150 G= G°’ + RT ln [GAP]/ [DHAP] G = 7.53 - 10.42 = -2.89 kJ/mol What does Gibbs Free Energy tell us? G compares enthalpy and entropy of the system. If G is negative, the reaction is spontaneous. A spontaneous reaction may proceed, but at what rate? Thermodynamics tells us nothing about the reaction rate. A reaction may be spontaneous ... ... but so slow, that it never happens. Problem: How do we get from Reactant to Product? Transition State Theory gives us the pathway between Reactant and Product using a few assumptions: 1) The rate of product formation is directly related to the population of the transition state. 2) There is a rapid equilibrium between reactant and transition state. The energy difference between transition state and reactant is the Gibbs free energy of activation, G . Note: Gibbs free energy for the reaction, G°’, is the difference between product and reactant free energy. Transition State Theory Transition state theory allows us to relate reaction rates (kinetics) to Gibbs Free Energy (thermodynamics) Given the Chemical Reaction A <-> X‡ -> P Assume that the rate of product formation is directly related to the concentration of transition state: VP = k[X‡] Assume rapid equilibrium A <-> X‡ Define equilibrium constant K‡ = [X‡]/[A] and Gibbs Free Energy G‡ = -RT ln K‡ Rearrange and solve for X : - G‡/RT = ln K‡ e- G‡/RT = K‡ e- G‡/RT = [X‡]/[A] [A] e- G‡/RT = [X‡] Reaction rate (product formation): V = k[X‡] Combine rate and G relations V = k[A] e- G‡/RT Maximal reaction rates are limited by the vibration of chemical bonds. Bond vibration rate: kbT/h = 6.2 x 1012 s-1 at 25°C Replace k with kbT/h V = kbT/h [A] e- G‡/RT Transition State Theory V = kbT/h [A] e- G‡/RT V is the reaction rate [A] is substrate concentration G‡ is free energy of activation This is remarkable similar to the empirically derived Arrhenius Equation: k = Ae E a RT k is the reaction rate A is the collision frequency factor (related to concentration) Ea is the activation energy The Rate of the Reaction is inversely and exponentially proportional to the Gibbs Free Energy of Activation. Enzymes and Free Energy • Enzymes have no effect on equilibrium – Enzymes cannot change G°’ • Enzymes accelerate the rate of a chemical reaction toward equilibrium • Given that K’eq = kforward/kreverse • Enzymes increase both the forward and reverse reaction rates • Reaction rates can be related to Gibbs free energy of activation = G‡ Activation Energy of an Enzymatic Reaction E+S ES ES‡ EP E+P Transition state intermediate, ES‡ G‡cat Enzymes lower the activation energy by stabilizing S‡ G‡cat How does an enzyme reduced the energy of the transition state S‡ an d accelerate the rate of a reaction? Substrate binding vs Transition state binding Lock and key versus Induced fit Organic Chemistry Review Electron Pushing The curved arrows are electron pairs which move from an electron rich atom toward an electron deficient atom. The number of bonds follows the standard rules of chemistry (Lewis structures and Valence Bond Theory). ...
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This note was uploaded on 03/26/2012 for the course CHEM 350 taught by Professor Lee during the Spring '08 term at SIU Carbondale.

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