Enzymes Definition and Classification Factors affecting enzymatic reactions Enzymes specificity Enzymes kinetics and mechanism of action Control of metabolic pathways Enzymes inhibition Enzymes in clinical diagnosis Enzymes and genetic diseases

Enzymes محاضرة الانزيمات 1& 2 Enzymes are proteins catalysts that increase the biochemical reactions rate, it lowers the activation energy figure (1), and they are not consumed during the reaction but may undergo physical changes. Figure (1): Enzymes are increase the reactions rate by decreasing the activation energy. Many reactions are required enzyme for normal biological activity of the cells. This biological activity would not proceed fast enough at the PH, and temperature of the body without these specialized proteins (enzymes). Enzymes often are known by common names obtained by the suffix “-ase” to the name of substrate or to the reaction they catalyze Table (1) indicate some enzyme examples Two important characteristics of enzyme as a catalysts are:- 1- The enzymes is not changed as a result of catalysis. 2- The enzyme dose not changed the equilibrium constant of the reaction but simply increase the rate at which the reaction approaches equilibrium. activation energy Table (1):- Enzyme Examples Enzyme Role Amylase A family of enzymes which assist in the breakdown of carbohydrates. Glucose oxidase Is an enzyme catalyze the oxidation of Glucose. Lipases AA family of enzymes which breakdown Lipids. Proteases Digestive enzyme which act on proteins in the digestive system. 1

Enzymes are important in clinical diagnosis:- Different cellular materials or tissues contain different enzymes, in each cell the enzymes are attached to the cell walls and membranes and are dissolve in the cytoplasm or sequestered in the nucleus and other sub cellular organelles including mitochondria, lysosomes, microsomes. From this any change in enzyme activity indicate a specific disease state or reflected tissue damage in a certain organ. Enzyme Terminology 1-Catalyst or Enzyme ( E ):- A substance that increase the rate of the reaction without being changed the overall process (reaction). 2-Substrates ( S ):- The materials that enzymes act upon, Table (2). Table (2): Some Types of Substrates. 3-Active site (catalytic site):- Enzymes have a specific areas (special pocket) on an enzyme where a substrate binds and catalysis takes place. This is called Active site formed by folding of the protein contains amino acid side chains which bind Substrate and form Enzyme-Substrate complex (ES). This binding thought to cause a conformational change in the enzyme to allows catalysis. (ES) complex is then converted to Enzyme and Product (P) as in Figure(2). E + S → ES → E + P Figure(2): Active site of Enzyme Product Substrate Enzyme Ammonia Urea Urease Derived proteins& Amino acids Protein Proteinases Oligosaccharides & Simple sugars Carbohydrates Carbohydrases Fatty acids Lipid Lipase 2 Glucose units Maltose Maltase Active site of Enzyme ← amino acids side chain.

E + S → ES → E + P E + S₁ + S₂ → E S₁ S₂ → E + P The enzymes are usually highly specific binding for their substrates:- a-Many enzymes recognized only single compound as a substrate Figure(2). E + S → ES → E + P Figure(2): Active site of Enzyme & General enzymatic reaction for one enzyme and substrate. E = Enzyme, S = Substrate, ES = Enzyme-Substrate complex. b-Some enzymes like those involved in digestion are less specific have more than one substrate Figure(3). E + S₁ + S₂ → E S₁ S₂ → E + P Figure(3): Active site of Enzyme & General enzymatic reaction for one enzyme and two substrate. E = Enzyme, S₁ = Substrate ₁, S₂ = Substrate ₂, ES = Enzyme-Substrate complex. Factors Affect The Enzyme Action: 1-The effect of Temperature on Enzyme activity: Temperature is speed up all reactions, besides at higher Temperature increase the rate of denaturation of enzymes. This higher Temperature break the disulphide bonds holding the structure of enzyme and casing changing the shape of the active site of the enzyme Figure(4) . Figure(4): The effect of Temperature on Enzyme action.

Fig(5): The effect of pH (H+ concentration) on Enzyme action. Factors Affect The Enzyme Activity: 2-The effect of pH (H+ concentration) on Enzyme action: Similarly to the temperature changes, enzymes are also sensitive to the changes in pH. Extreme values (both low and high) can lead to the denaturation of the enzyme molecules. Each enzyme has its pH optimum, which is a value of pH when the enzyme activity is the highest Fig(5). Fig(5): The effect of pH (H+ concentration) on Enzyme action. 3- The effect of Enzyme Concentration on Enzyme action: Assume the amount of substrate is not Limiting, an increase in enzyme concentration causes an increase in the reaction rate. Fig (6). Fig (6): Pepsin enzyme Arginase

The Models Of Enzyme Action:- LOCK AND KEY MODEL: The lock and key model of enzyme action, proposed was drawn into a closely matching cleft on enzyme molecule. Symbolic representation of the lock and key model of enzyme action. 1- A substrate is drawn into the active sites of the enzyme. 2-The substrate shape must be compatible with the enzyme active sites in order to fit then reacted upon. 3-The enzyme modifies the substrate causing broken substrate and releasing products Figure(9). Figure(9): The lock and key model. INDUCED FIT MODEL: More recent studies have revealed that the process is involve an induced fit. 1-Two substrate molecule are drawn into the cleft of enzyme. 2- The enzyme changes their shapes to combine together by weak chemical bonds 3-The product released by returns the enzyme to its normal shape, and being ready to undergo more reactions figure(10). Figure(10):Induced fit module. Enzyme Enzyme product substrates Enzyme