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Bio 98 - Leture 8 Enzymes I Enzymes 1. Selective catalysis and regulation of metabolic rxns - enzymes are unchanged by the reaction - some require co-factors (small organic molecules &/or metals such as Ca, Zn, Cu or Fe, or heme) 2. Most are proteins; some RNAs can also catalyze rxns 3. Example of extreme catalytic efficiency: “catalase” Reaction: 2 H2O2 2 H2O + O2 Catalyst Relative rate None 1 Fe3+ 1,000 Catalase enzyme (heme) 109 (40,000,000/sec) 3D structure of catalase Reaction: 2 H2O2 2 H2O + O2 Compound I Reaction scheme of catalase Enzymes 4. Another example of extreme catalytic efficiency: “triosephosphate isomerase” DHAP Reaction Free energy profile DAP 3D structure of triosephosphate isomerase (TIM barrel) The enzyme is so efficient that it is said to be catalytically perfect: It is limited only by the rate the substrate can diffuse into and out of the enzyme’s active site! 3D structure of triosephosphate isomerase (TIM barrel) Uncatalyzed reaction: G (free energy) S P (transition state) S‡ G‡ S P G transition state free energy (activation energy) overall reaction free energy change Reaction coordinate 1. G determines where equilibrium lies. 2. G‡ determines the rate at which equilibrium is achieved. Enzyme-catalyzed reaction: G (free energy) S E P S‡ ES‡ G‡ E+S E+P G Reaction coordinate 1. Enzymes do not alter the equilibrium or G. 2. They accelerate reactions by decreasing G‡. 3. They accomplish this by stabilizing the transition state(s). Models of Enzyme-Substrate Interaction Emil Fischer, 19th century Daniel Koshland, 20th century (sequential model for Hb coop.!) The “Stickase” Enzyme Factors Contributing to Rate Enhancement by Enzymes 1. Concentration - effective molarity in the active site. k2 (second order rate constant) k1 (first order rate constant) Effective molarity = k1[s-1] / k2 [M-1s-1] = k1 / k2 [M] 2. Orientation - increases the probability of correct bond or orbital alignment. A A B B enzyme 3. Strain - weakening of bonds by distortion - exemplified by “stickase” model 4. Chemical catalysis (a catch-all term) • major factor for most enzymes • major types: acid-base, covalent, metal ion • a given enzyme may use several types of chemical catalysis in its mechanism Combines with the final slide of the lecture Chymotrypsin is a serine protease that cleaves a peptide at Phe/Tyr/Trp (C) leaving a COO- on Phe/Tyr/Trp R2 R22 R2 R2 To aid in the understanding of slide 15: Acid-base forms of amino acid side chain