Enzymes & Enzyme Kinetics 1 الفريق الطبي األكاديمي

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1 Enzymes & Enzyme Kinetics 1 الفريق الطبي األكاديمي Lectuer one : Done by Shady Soghayr Corrected by Gharam Al-Khalaileh Lectuer two : Will Done by Rand Khlaifat & hanan jamal كلية الطب البشري البلقاء التطبيقية / املركز ومن أحياها /

2 Enzymes - Basic Concepts and Kinetics ( outline for the next 4 lecture doctor skip it ) Enzymes as Catalys Enzyme rate enhancement / Enzyme specificity Enzyme cofactors Free Energy G determines the direction a reaction proceeds If G <0, the reaction proceeds forward as written If G >0, the reaction proceeds backward as written If G = 0, the reaction is at equilibrium Note that equilbrium DOES NOT mean equal concentrations of reactants and products. Rather, equilbrium means that the concentration of reactants and products does not change over time. G0' G0' is related to G. It is the same as G under standard conditions Thus, the sign of G0' determines the direction of a reaction ONLY under standard conditions. G determines the direction of a reaction under any conditions, including standard conditions Calculations G = G0' + RT ln[products]/[reactants], w R is the gas constant and T is the temperature in Kelvin At equilibrium, G = 0, so G0' = -RT ln[products]/[reactants] = - RTln K'eq Thus, G0' is related to the equilibrium constant for a reaction Relation between G0' and K'eq at 25 C Mechanisms Enzymes speed reactions Page 1

3 Enzymes act by decreasing activation energy Reaction velocity versus substrate concentration Residues at active site / Hydrogen bonds with substrate Fischer lock&key model of catalysis / Koshland induced fit model Michaelis-Menten Model Initial velocity determination KM determination LineWeaver-Burk plot KM values of some enzymes / Turnover numbers Substrate preferences of chymotrypsin Diffusion-controlled enzymes Multiple Substrate Reactions Sequential displacement Ordered example / Schematic Random example / Schematic Double displacement Allosteric enzyme kinetics Enzyme Inhibition Uninhibited vs. Competitive vs. Uncompetitive vs. Non-Competitive Methotrexate and Tetrahydrofolate Kinetics of a competitive inhibitor (V vs. [S]) and (Lineweaver-Burk) Kinetics of a non-competitive inhibitor (V vs. [S]) and (Lineweaver-Burk) Serine modification by DIPF Suicide inhibition Triose phosphate isomerase by bromoacetal phosphate Glycopeptide transpeptidase by penicillin You must be able to: the aims 1. Compare uncatalyzed reactions with enzymatic catalyzed reactions and appreciate the rate of enhancement done by enzymes Page 2

4 2. Define substrate, substrate binding site and active site 3. State and understand the steps in enzyme catalytic reactions: E+S <=> ES <=> ES* <=> EP <=> E+P 4. Define the terms Binding Specificity, Flexibility, Electronic Environment, and Coenzymes and recognize their importance in enzyme action 5. Differentiate between substrate binding models; fisher and koshland, 6.. 6Correlate tension to koshland mechanism 7. Understand the energy profile of catalyzed reactions 8. Know that enzymes lower the activation energy without affecting the energy of the whole reaction and thus not affecting K equiliprium 9.. 9State the types of enzymatic reactions and know what happened in each case Define and understand the ordered, random, and ping-pong reactions of the multiple substrate multiple products Understand that n kinetics means measuring rate of product formation, specifically Kcat You shouldn t memorize this table enzymes enhance/ increases the rate of the reaction The enzymes are important for the body because the metabolism either for oxidation or syntheses depend on enzymes and clevises For ex :- The reaction of OMP decarboxylase ( which is important in DNA syntheses ) take 78 m years to complete without enzyme but take 28 * Page 3

5 Enzymatically Catalyzed Reactions Catalyses could be enzymatic or not enzymatic. in test tubes its chemical catalyses. While in our bodies they are enzymatic catalyses Enzymatic catalyses has millions of bower/rating to speed the reaction than chemical catalyses The enzymes catalyses enhancing the rate of reaction by binding specific substrate to their binding sight while in the chemical catalyses they need to just face each other Substrate: the compound or the reactant or molecules that bind to the enzyme Every enzyme has it's specific substrates Hexokinase enzyme its substrate is glucose & ATP and can't bind lactose & CTP Fructokinase will only bind fructose The active site : a region on the enzyme that is compose from chemical group from amino acid that bind to a specific chemical compound Page 4

6 The substrate binding with the substrate binding site in the enzyme so the reaction will take place in this rang,so what will happen?! 1. Its stricture will change & maybe 2 substrate bind with the enzyme so so it will close the substrates to each other 7 will create the chemical environment for the reaction to take place so enhance the reaction Lectuer 2 مالحظة :- محاضرة يوم االحد 25\9 رح تنزل على هاد الشيت بحيث يشمل كل تشابتر االنزيم GOOD LUCK Page 5

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