Enzymes Basics of Biochemistry PDF

Department of Biochemistry Faculty of Medicine – Umm Alqura University Basics of Biochemistry First Year – MBBS & Dentistry program  Enzymes properties and Classification Learning Objectives: By the end of the lecture, the student should be able to: Define enzymes and related t...

Department of Biochemistry Faculty of Medicine – Umm Alqura University Basics of Biochemistry First Year – MBBS & Dentistry program  Enzymes properties and Classification Learning Objectives: By the end of the lecture, the student should be able to: Define enzymes and related terms ( active site, apoenzyme, holoenzyme, prosthetic group, enzyme specificity, ….etc). Illustrate the classification of enzymes. Explain the Mechanism of action and the energy of activation. Describe inhibition: (reversible, irreversible, competitive and non- competitive). Enzymes: Nature and Feature  They are proteins in nature and they are catalysts of biological origin Catalyst Any substance which accelerates the rate of chemical reaction without being change in equilibrium They are highly specific. One enzyme will only carry out one of the many reactions of which a substrate is capable. Not altered or consumed during reaction Have unique three-dimensional shapes that fit the shapes of reactants. They are effective in tiny amounts. One enzyme molecule may convert 1000 molecules of substrate a minute, and some are known to convert 3 million in a minute. Enzymes: Names and Terms: The name of an enzyme: Usually ends in –ase. Identifies the reacting substance. Sucrase catalyzes the hydrolysis of sucrose. Lipase catalyzes the hydrolysis of lipids. Describes the function of the enzyme. Oxidases catalyze oxidation. Hydrolases catalyze hydrolysis. Could be a common name, particularly for the digestion enzymes such as pepsin and trypsin. APOENZYME and and Enzymes: Names HOLOENZYME Terms: Apoenzyme and Holoenzyme:  Apoenzyme: The enzyme without its non protein moiety (The enzyme in inactive form).  Holoenzyme: The enzyme with its non protein component (The enzyme in the active form).  This non-protein part may be loosely attached to the protein part, and then it is called coenzymes or cofactor. Enzymes: Names and Terms: Co-factors Enzymes: Names and Terms: Zymogens (proenzymes): Are inactive forms of enzymes. Are activated when one or more peptides are removed. Digestive enzymes are released in inactive forms (zymogens). This is necessary to prevent the digestive enzymes from digesting the cells that produce them. In a zymogen, part of the protein blocks the active site of the enzyme. Cleaving off this peptide activates the enzyme. Enzymes: Names and Terms: Active Site (Catalytic Site) Is a region within an enzyme that fits the shape of molecules called substrates. Contains amino acid R groups that align and bind the substrate. Releases products when the reaction is complete. Enzymes action: Enzymes : enzymatic reaction:- Increase the rate of reaction by lowering the energy of activation. activation energy – Minimum amount of energy needed to start a chemical reaction. Catalyze nearly all the chemical reactions taking place in the cells of the body. Mechanism of enzyme action Lock & Key Model In the lock-and-key model of enzyme action: The active site has a rigid shape. Only substrates with the matching shape can fit. The substrate is a key that fits the lock of the active site. Classification of Enzymes Six main classes on the basis of the reaction they catalyze Class Reactions catalyzed Oxidoreductases Oxidation-reduction. Add or remove hydrogen atoms. Transfer groups or atoms between donor and acceptor Transferases molecules.(Ex: Kinases, Phosphatases) Hydrolases Hydrolysis by adding water across a bond. Add/remove atoms to/from a double bond. Lyases (Adding water, ammonia, or carbon dioxide across double bonds or remove them forming double bonds). Isomerases Rearrange atoms Two chemical groups are joined (or ligated) with the Ligases use of energy from ATP Oxido-reductases Include all enzymes that catalyze oxidation reduction reaction between two substrates. e.g: Dehydrogenases Oxidases Reductases Transferases Catalyze the transfer of a functional group from one molecule (donor) to another (acceptor). e.g.: Transaminases catalyze transfer of an amino group Kinases (phosphotransferases) catalyze transfer a phosphate group. Hydrolases and Lyases Isomerases and Ligases Enzyme Specificity Enzymes may recognize and catalyze:  A single substrate.  A group of similar substrates.  A particular type of bond. Isoenzymes  Isoenzymes catalyze the same reaction in different tissues in the body.  Lactate dehydrogenase, which converts lactate to pyruvate, (LDH) consists of five isoenzymes. Factors Affecting Enzymatic Activity 1- Temperature: Enzymes are most active at an optimum temperature (usually 37°C in humans). They show little activity at low temperatures. Enzymes lose activity at high temperatures as denaturation occurs. Factors Affecting Enzymatic Activity 2- pH Each enzyme exhibits peak activity at narrow pH range (optimum pH). Enzymes contain R groups of amino acids with proper charges at optimum pH. Enzymes lose activity in low or high pH as tertiary structure is disrupted. Factors Affecting Enzymatic Activity 3- Enzyme Amount The rate of reaction increases as enzyme amount increases (at constant substrate concentration). At higher enzyme concentrations, more substrate binds with enzyme. Factors Affecting Enzymatic Activity 4- Substrate Concentration The rate of reaction increases as substrate concentration increases (at constant enzyme concentration). Maximum activity occurs when the enzyme is saturated. Enzymes: nature and Feature: Enzyme Inhibition Inhibitors: o Are molecules that cause a loss of catalytic activity. o Prevent substrates from fitting into the active sites. o Two broad classes of enzyme inhibitors: A. Reversible B. Irreversible. A- Reversible Inhibition 1- Competitive Inhibition A competitive inhibitor: Has a structure like the substrate. Competes with the substrate for the active site. Has its effect reversed by increasing substrate concentration. A- Reversible Inhibition 2- Noncompetitive Inhibition A noncompetitive inhibitor: Has a structure different than the substrate. Distorts the shape of the enzyme, which alters the shape of the active site. Prevents the binding of the substrate. Cannot have its effect reversed by adding more substrate. B- Irreversible Inhibition Loss of all enzymatic activity Toxic substance (irreversible inhibitor) forms a covalent bond with an amino acid in the active site. Prevents the substrate from entering the active site. Prevents the catalytic activity. Examples: insecticides and nerve gases inhibit the enzyme acetylcholinesterase (needed for nerve conduction).