Medical Enzymology Lecture Notes PDF

BMS: 131 Lecture No: 5 Title: Medical enzymology Medical enzymology Dr Wel Elayat  Intended Learning Outcomes (ILOs): By the end of this lesson, the student should be able to: 1. Define enzymes. 2. Identify enzyme nomenclature, classes, and enzyme commission code. 3. Identify some enzyme-...

BMS: 131 Lecture No: 5 Title: Medical enzymology Medical enzymology Dr Wel Elayat  Intended Learning Outcomes (ILOs): By the end of this lesson, the student should be able to: 1. Define enzymes. 2. Identify enzyme nomenclature, classes, and enzyme commission code. 3. Identify some enzyme-related terms: apoenzyme, holoenzyme, coenzyme, prosthetic group, and cofactor. 4. Comment on general properties of enzymes: specificity, catalytic efficiency, subcellular localization, active site, and catalytic sites. 5. Describe the mechanism of enzyme action (catalysis).  WHAT ARE ENZYMEs ? Enzymes Are:  biological catalyst increase the rate of a chemical reaction.  mostly protein in nature (exception: RNA with catalytic activity or ribozymes e.g peptidyl transferase) required in very small amounts.  not changed during the overall chemical reaction.  Why Are Enzymes So Important? All functions of living tissues depend on chemical reactions. A car engine gets energy by burning a fuel, a combustion reaction. Our cells clearly cannot do the same. Thanks to enzymes, all our biological reactions proceed at 37oC, within our tissue environment, at the required rate. Almost all reactions in living tissues are catalyzed by enzymes.  Nomenclature of enzymes Two main systems for nomenclature of enzymes: 1) Common, short name Most commonly used enzyme names have the suffix “-ase” attached to the substrate o e.g : Urease , Glucosidase Or to a description of the action performed o e.g: lactate dehydrogenase and adenylyl cyclase Some old enzyme names give no indication to the substrate or the action of the enzyme, o e.g: Pepsin, the proteolytic enzyme of the stomach.  Nomenclature of enzymes 2) Systematic name (unambiguous) For an enzyme, the suffix -ase is attached to a fairly complete description of the chemical reaction catalyzed, including the names of all the substrates. Substrate Coenzyme Action performed  e.g., lactate: NAD+ oxidoreductase = lactate dehydrogenase. Systematic names are long and not commonly used. lactate: NAD+ oxidoreductase = lactate dehydrogenase  The six major classes of enzymes according to the International Union of Biochemistry and Molecular Biology (IUBMB  Lyases catalyze the cleavage of a covalent bond, with formation of molecules that contain a double bond, or the reverse reaction. Ligases catalyze binding of two molecules by a covalent bond using energy (ATP). Which Class Lactate Dehydrogenase Belongs To?: 1. Oxidoreductase 2. Lyase 3. Transferase 4. Ligase 5. Hydrolase  Enzyme Commission code (EC code) EC numbers specify enzyme-catalyzed reactions. The EC codes are assigned by IUBMB Every enzyme code consists of the letters “EC” followed by four numbers separated by periods. The first number denotes one of the six enzyme classes. An example is hexokinase whose systematic name is ATP:D-hexose 6- phosphotransferase (EC 2.7.1.1): – 2= class name (transferase). – 7= subclass (phosphotransferase). – 1= the acceptor is OH group – 1= D-hexose is the phosphate acceptor.  Hexokinase (short name) ATP:D-hexose 6- phosphotransferase (Systemic name) EC 2.7.1.1  Holoenzyme and apoenzyme Apoenzyme : the protein portion of the enzyme only Holoenzyme : apoenzyme + non protein part  Substrate-binding site (Active site) What is the active site? It is a special pocket or cleft within the enzyme It is formed by folding of the protein, contains amino acid side chains that participate in substrate binding and catalysis.  Substrate-binding site (Active site) The active site can be formed by amino acids far away in the primary structure and brought together by protein folding of the protein in its tertiary or quaternary structures  Enzyme–Substrate (ES) complex The substrate binds the enzyme, forming an enzyme–substrate (ES) complex. Binding of the substrate causes a conformational change in the enzyme (induced fit model) that allows catalysis. ES is converted to an enzyme–product (EP) complex that dissociates to enzyme and product or products.  Allosteric site Other site away from active site where small molecules can bind resulting in increased or decreased activity of enzyme  Enzyme Specificity Enzymes are highly specific, interacting with one or a few substrates and catalyzing only one type of chemical reaction. Specificity may be encountered to one optical types of substrates, – e.g., l- or d-forms or specificity to only one isomer, e.g., α – or β-forms. Some enzymes also show specificity to one hydrogen carrier, e.g., NAD+, FAD, or NADP+.   subcellular Localization within the cell Many enzymes are localized in specific organelles within the cell (compartmentalization). This provides a favorable environment for a reaction or a metabolic pathway. Glycolysis occurs in cytosol But Urea cycle and gluconeogenesis and Krebs(TCA) occurs in occur in both cytosol Mitochondrion exclusively and Mitochondrion- Partially  Catalytic efficiency Enzyme-catalyzed reactions are highly efficient, proceeding from 103–108 times faster than uncatalyzed reactions. Turnover number (Kcat) The number of molecules of substrate converted to product per enzyme molecule per second is called the turnover number, or kcat, and typically is 102–104/s.  A. Energy changes that occur during the reaction Energy Barrier of a chemical Reaction (Activation Energy) It is the amount of energy needed to raise the energy level of the ground state of reactants to the energy level of the transition state (high-energy intermediate )  What is the Transition State? It is the point at which the reaction event (bond breaking, bond formation, etc.) can occur.  Energy Barrier of a chemical Reaction (Activation Energy) Because of the high free energy of activation, the rates of uncatalyzed chemical reactions are often slow. The lower the free energy of activation, the more molecules have sufficient energy to pass through the transition state, and, therefore, the faster the rate of the reaction. A. Energy changes that occur during the reaction An enzyme allows a reaction to proceed rapidly by providing an alternate reaction pathway with a lower free energy of activation. So enzymes accelerate the rate of the reaction by lowering the free activation energy  A. Energy changes that occur during the reaction The enzyme does not change the free energies of the reactants or products (ΔG) and, therefore, does not change the equilibrium of the reaction Enzymes, however, accelerate the rate by which equilibrium is reached. Free energy (G): It is an amount of energy capable of doing work during a reaction. Free-energy change (ΔG ): is a measure of the chemical energy available from a reaction ΔG = Gproducts - Greactants  AB + C ∆G is the same in both enzyme catalyzed and un-catalyzed reactions  B. Active site facilitates catalysis by 1. Causing transition state (T*) stabilization, favoring product formation. 2. Providing catalytic groups that enhance the probability that transition state is formed  References for further readings Lippincott Illustrated Review Integrated system 3rd edition Lippincott Illustrated Review 6th edition Oxford Hand book of Medical Science 2nd edition THANK YOU 36 Full Name​​ [email protected] www.gu.edu.eg