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Chapter 8.5 Notes How Are Enzyme Activities Regulated ?
EQ
-homeostasis: the maintenance of stable internal conditions -chemical reactions operate within metabolic pathways in which the product of one reaction is a reactant for the next -The presence and activity of enzymes determine the “flow” of chemicals through different metabolic pathways -Regulation of the rates at which thousands of different enzymes operate contributes to homeostasis within an organism. -Computer algorithms are used to model these pathways and show how they mesh in an interdependent system - Such models can help predict what will happen if the concentration of one molecule or another is altered. This new field of biology is called systems biology, and it has numerous applications. Enzymes can be regulated by inhibitors -chemical inhibitors can bind to enzymes, slowing down the rates of the reactions they catalyze -Naturally occurring inhibitors regulate metabolism; artificial ones can be used to treat disease, to kill pests, or to study how enzymes work. IRREVERSIBLE INHIBITION -competitive inhibitor: a n inhibitor covalently binds to certain side chains at the active site of an enzyme, it will permanently inactivate the enzyme by destroying its capacity to interact with its normal substrate -noncompetitive inhibitor binds to an enzyme at a site distinct from the active site - binding causes a change in the shape of the enzyme that alters its activity. Figure 8.14 Allosteric enzymes control their activity by changing shape
What is the difference between reversible and irreversible enzyme inhibition?
Figure 8.15
Figure 8.16
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How are allosteric enzymes regulated?
Explain the concept of feedback inhibition.How might the reactions shown in Figure
-Allosteric regulation:occurs when an effector molecule binds to a site other than the active site of an enzyme, inducing the enzyme to change its shape. The change in shape alters the affinity of the active site for the substrate, and so the rate of the reaction is changed SHAPES: • The active form of the enzyme has the proper shape for substrate binding. • The inactive form of the enzyme has a shape that cannot bind the substrate.
Figure 8.17 Effectors: can influence which form the enzyme takes: • Binding of an inhibitor to a site separate from the active site can stabilize the inactive form of the enzyme, making it less likely to convert to the active form. • The active form can be stabilized by the binding of an activator to another site on the enzyme. -Some enzymes have multiple subunits containing active sites, and the binding of substrate to one of the active sites causes allosteric effects. -an allosteric enzyme with multiple active sites and a non allosteric enzyme with a single active site differ greatly in their reaction rates when the substrate concentration is low -For a non allosteric enzyme, the plot looks like that in Figure 8.18A -The plot for a multisubunit allosteric enzyme is radically different, having a sigmoid (S-shaped) appearance - the final product acts as a noncompetitive inhibitor of the first enzyme in the pathway. This mechanism is known as feedback inhibition or end-product inhibition
Figure 8.18 Allosteric effects regulate metabolism -Metabolic pathways typically involve a starting material, various intermediate products, and an end
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8.19 fit into a systems diagram such as the one shown in Figure 8.14?
product that is used for some purpose by the cell. -The first step in a pathway is called the commitment step, meaning that once this enzyme-catalyzed reaction occurs, the “ball is rolling,” and the other reactions happen in sequence, leading to the end product. -One way to avoid this problem is to shut down the metabolic pathway by having the final product inhibit the enzyme that catalyzes the commitment step
Figure 8.19 Enzymes are affected by their environment -Enzymes enable cells to perform chemical reactions and carry out complex processes rapidly without using the extremes of temperature and pH employed by chemists in the laboratory pH AFFECTS ENZYME ACTIVITY
Figure 8.20 -The rates of most enzyme-catalyzed reactions depend on the pH of the solution in which they occur. While the water inside cells is generally at a neutral pH of 7, the presence of acids, bases, and buffers can alter this. Each enzyme is most active at a particular pH; its activity decreases as the solution is made more acidic or more basic than the ideal (optimal) pH -One factor is ionization of the carboxyl, amino, and other groups on either the substrate or the enzyme. In neutral or basic solutions, carboxyl groups (—COOH) release H+ to become negatively charged carboxylate groups (—COO–). On the other hand, in neutral or acidic solutions, amino groups (—NH2) accept H+ to become positively charged —NH3 + groups TEMPERATURE AFFECTS ENZYME ACTIVITY -warming increases the rate of a chemical reaction because a greater proportion of the reactant molecules have enough kinetic energy to provide the activation energy for the reaction. Enzyme catalyzed reactions are no different -However, temperatures that are too high inactivate enzymes, because at high temperatures enzyme molecules vibrate and twist so rapidly that some of their noncovalent bonds break
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-When an enzyme’s tertiary structure is changed by heat it loses its function. Some enzymes denature at temperatures only slightly above that of the human body, but a few are stable even at the boiling point (or freezing point) of water -Individual organisms adapt to changes in the environment in many ways, one of which is based on groups of enzymes, called ​isozymes, that catalyze the same reaction but have different chemical compositions and physical properties
Figure 8.21 Summary:
The rates of most enzyme-catalyzed reactions are affected by interacting molecules (such as inhibitors and activators) and by environmental factors (such as temperature and pH). Metabolism is organized into pathways in which the product of one reaction is a reactant for the next reaction. Each reaction in the pathway is catalyzed by an enzyme.The end product of a metabolic pathway may inhibit an enzyme that catalyzes the commitment step of that pathway.