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The Chemical Reactions of Life

The Chemical Reactions of Life
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Dr.SamuelHunt,United Arab Emirates,Teacher
Published Date:21-07-2017
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UNIVERSITY OF OXFORD DEPARTMENT OF CHEMISTRY Basic Enzymology Dr Emily Flashman http://flashman.chem.ox.ac.uk 2 Lectures – Trinity Term 2015 Enzymology: Lecture 1 Topics to be Covered: Lecture 1: Introduction to enzymes The importance of enzymes in catalysing the chemical reactions of life. How enzymes promote catalysis Typical enzyme-catalysed reactions Enzyme efficiency: selectivity, co-factors and control. Lecture 2: Principles of enzyme catalysis Thermodynamics of enzyme-catalysed reactions Transition state stabilisation Case Study - Triose phosphate isomerase Enzymology: Lecture 1 Topics to be Covered: No prior knowledge other than content of Oxford Chemistry course. No text books are essential but the following are useful: Foundations of Chemical Biology, Oxford, Chemistry Primer (Dobson, Gerrard, Pratt, OUP) Access to a modern Biochemistry textbook: Voet and Voet, Biochemistry (4th Edition, Wiley) Enzymology: Lecture 1 Objectives of the Course: • To provide an introduction to enzyme catalysis and related protein functions, focusing on chemical principles • To connect mechanistic synthetic chemistry with biology • To demonstrate that chemical principles underlie biology and that understanding and manipulating this chemistry is fascinating and the basis of multiple applications. Enzymology: Lecture 1 This course is NOT about remembering complex structures But About understanding the chemical principles that control biology "Enzyme catalysis: not different just better"(Jeremy Knowles) Enzymology: Lecture 1 • One of the most important targets for pharmaceuticals • Intrinsic in human biology - manipulation • Fermentation of pharmaceuticals and fine chemical • Useful in synthesis, especially for resolutions / asymmetric reactions, e.g. resolutions by enantiospecific -amino acid acylase • Wide ranging applications in society, e.g. food industry, washing powders • Bioremediation • An understanding of enzyme catalysed reactions may help us to design useful unnatural ‘biomimetic’ catalysts, based on knowledge of enzyme structures / mechanisms. The Chemical Reactions of Life Enzymology: Lecture 1 The Chemical Reactions of Life Enzymology: Lecture 1 The Chemical Reactions of Life Enzymology: Lecture 1 Hexokinase creates right conditions for nucleophilic attack of C6- OH on ATP The enzyme promotes an otherwise unfavourable reaction that is vital in energy-generating glycolysis process. The Chemical Reactions of Life Enzymology: Lecture 1 Enzymes are important How Enzymes Promote Catalysis Enzymology Lecture 1 Enzymes are protein-based catalysts – they facilitate chemistry • ‘Free enzymes’ are often globular proteins, but enzymes can be part of large complexes or embedded in membranes. • We will focus on ‘simple’ enzymes that catalyse ‘simple’ reactions, but the same principles of catalysis apply in all cases. How Enzymes Promote Catalysis Enzymology Lecture 1 Bringing enzyme and substrate(s) together in a favourable conformation to promote the reaction. Enzymes have ACTIVE SITES • a 3D cleft or crevice with precisely defined arrangement of atoms • relatively small area of enzyme • substrates bind via multiple weak interactions How Enzymes Promote Catalysis Enzymology Lecture 1 Enzymes are biological catalysts: Increase the rate at which a reaction reaches equilibrium Stabilise the transition state of a reaction relative to the uncatalysed reaction Enzymes are finely tuned for specificity in substrate binding and optimal arrangement of catalytic groups How Enzymes Promote Catalysis Enzymology Lecture 1 Amino acid side chains (and the peptide backbone) provide a repertoire of functional groups for catalysis and binding How Enzymes Promote Catalysis Enzymology Lecture 1 Enzymes are more efficient than chemical catalysts: 1. Higher reaction rates – by several orders of magnitude 2. Milder reaction conditions – low temps, atm pressure, neutral pH 3. Greater reaction specificity – no side products 4. Capacity for control – catalytic activity can vary in response to local conditions Typical Enzyme-Catalysed Reactions Enzymology Lecture 1 Enzymes catalyse both simple reactions and reactions that are ‘impossible’ for synthetic chemistry. Triose phosphate isomerase (‘easy’ reaction) Proline hydroxylase (‘difficult’ reaction) Typical Enzyme-Catalysed Reactions Enzymology Lecture 1 Penicillin biosynthesis catalysed by isopenicillin N synthase • Fermented on a ton-scale by fermentation • Fermented pencillins are used directly and others are produced by modification of fermented penicillins • Single step reaction into highly functionalised penicillin • Organic synthesis is not competitive (1% multistep route) Typical Enzyme-Catalysed Reactions Enzymology Lecture 1 Enzymes catalyse (most) of the ‘fundamental’ reactions of organic synthesis Example 1 – the S 2 reaction by a methyltransferase enzyme NTypical Enzyme-Catalysed Reactions Enzymology Lecture 1 Example 2 – the Michael reaction (conjugate addition) by enoyl CoA hydratase Enzyme Efficiency Enzym Enzym olo olog gy y Lect Lect uru e re 1 1 How do enzymes manage to be such efficient catalysts? 1. Substrate specificity • Stereospecificity • Geometric specificity 2. Coenzymes 3. Control of activity: regulating activity in time and space