Lecture Set 14- Enzymes - Canvas - PDF

Enzymes  Enzymes Are Catalysts Most biologically important reactions occur very slowly in the absence of a catalyst. Some reactions are slow because of an energy barrier called the activation energy (Ea). This is the amount of energy required to start a reaction. Catalyst: Accelerat...

Enzymes  Enzymes Are Catalysts Most biologically important reactions occur very slowly in the absence of a catalyst. Some reactions are slow because of an energy barrier called the activation energy (Ea). This is the amount of energy required to start a reaction. Catalyst: Accelerates a reaction without being permanently changed in the process. Enzymes: Biological catalysts that speed up and control chemical reaction rates.  Properties of Enzymes Most enzyme names end in ”- 1. Most enzymes are proteins (exception – ribozymes) ase” (e.g., kinase) 2. Enzymes lower the activation energy of a reaction Enzymes do not change the nature of a reaction (i.e., DG). 4. Enzymes are very specific for the reactions they catalyze The enzyme-substrate complex is held together by hydrogen bonds, electrical attraction, or hydrophobic interactions (and sometimes covalent bonds) Enzyme-Catalyzed Reactions Enzymes are not consumed by the reaction and can act repeatedly. Reactants that are acted upon by enzymes are called “substrates”.  Enzymes Activation Energy: Even though a reaction is energetically favorable (DG < 0), an initial investment of energy is usually required. Enzymes lower the energy barrier for reactions. Enzymes do not change the ΔG for a reaction.  Activation Energy and The Transition State Activation energy changes the reactants into unstable forms with higher free energy—transition state species. Activation energy can come from heating the system— the reactants have more kinetic energy. Enzymes lower the energy barrier by bringing the reactants together.  Enzyme Shape and the Active Site In an enzyme-catalyzed reaction, the substrate binds to the active site of the enzyme. Active Site: The catalytic center of the enzyme. Shape of enzyme active site allows a specific substrate to fit—the “lock and key.” Many enzymes change shape when they bind to the substrate— induced fit. The active site binds the substrate(s) and helps to stabilize the transition state, lowering the activation energy. Active Site Formation Figure 6.11 Life at the Active Site (A) Enzymes orient substrate molecules, bringing together the atoms that will bond. Enzymes can stretch the bonds in substrate molecules, making them unstable. Enzymes can temporarily add chemical groups to substrates. Enzymes can lower the activation energy of a reaction by bringing substrates together Enzymes provide a template upon which the two substrates are brought together in the proper position and orientation to react with each other. Substrate 1 Substrate 2 Enzymes can lower the activation energy of a reaction by bringing substrates together Figure 6.14 Catalyzed Reactions Reach a Maximum Rate The rate of a catalyzed reaction depends on substrate concentration. Concentration of an enzyme is usually much lower than concentration of a substrate. At saturation, all enzyme is bound to substrate—maximum rate. Rate can be used to calculate enzyme efficiency: molecules of substrate converted to product per unit time—also called turnover. Ranges from 1 to 40 million molecules per second! Properties of Enzymes The rate of a catalyzed reaction depends on substrate concentration. Concentration of an enzyme is usually much lower than the concentration of substrate. At saturation, all enzyme is bound to substrate—maximum rate. Enzymes do not alter the DG of a reaction  Regulation of Enzyme Activity Several factors can regulate (activate or inhibit) enzyme activity:  Temperature Environmental Factors  pH  Cofactors: Accessory molecules required for optimal enzyme activity.  Inhibitors: Are essential for regulating metabolic pathways. Can be reversible or irreversible Competitive Inhibitor: Looks like substrate and binds to active site of enzyme Non-competitive Inhibitor: Binds to other site on enzyme  Regulation of Enzyme Activity - Temperature Every enzyme has an optimal temperature. At high temperatures, noncovalent bonds begin to break. An enzyme can lose its tertiary structure and become denatured.  Protein Unfolding - Denaturation Conditions that affect secondary and tertiary structure include: High temperature pH changes Denaturation: loss of 3- dimensional structure and thus function of the protein Regulation of Enzyme Activity - pH Every enzyme has an optimal pH at which it functions. pH influences the ionization of functional groups.  Enzyme Inhibitors Substances that block the action of an enzyme. Two important types of inhibitors: 1. Competitive 2. Noncompetitive  Enzyme Inhibitors Substances that block the action of an enzyme. Two important types of inhibitors: 1. Competitive 2. Noncompetitive An enzyme activator is a molecule that accelerates the activity of an enzyme Irreversible inhibition: inhibitor covalently bonds to side chains in the active site—permanently inactivates the enzyme. Example: DIPF or nerve gas Effects of Nerve Gas: excessive muscle contraction followed by paralysis, secretions, seizures and death by Irreversible Inhibition (Covalent modification) Irreversible inhibitors bind permanently to their target enzyme, often via a covalent bond that influences catalysis  Metabolic Pathways Metabolic reactions are organized into pathways that are an orderly series of enzymatically-controlled reactions. The first reaction is the commitment step—other reactions then happen in sequence. Feedback (negative) Inhibition: The final product may inhibit the enzyme needed for the commitment step, which shuts down the pathway—end product inhibition.  Metabolic Pathways Thousands of chemical reactions are occurring in cells simultaneously. The reactions are organized in metabolic pathways. Each reaction is catalyzed by a specific enzyme. The pathways are interconnected. Regulation of enzymes and thus the rates of reactions helps maintain internal homeostasis. ontrol of Metabolic Pathways Feedback inhibition is a common method for regulating metabolic pathways. The end product acts as an inhibitor of an enzyme earlier in the pathway. Thus, when the product is abundant the pathway is turned off. When rare, the pathway is active.