Module 2: Lesson 2: Enzymes Flashcards
One of the key roles that proteins play in living systems is to act as enzymes in chemical reactions. An enzyme is a molecule with a specific shape and structure that facilitates chemical reactions between other molecules, while not being altered or “used up” by the reaction. This allows one enzyme to perform the same reaction many times. Because of the presence of the enzyme, the chemical reaction takes place at a much faster rate than it otherwise would.
<p>The role of enzymes in the chemical reactions of a cell is similar to the role of a broker or an agent in a business deal. The broker brings together a buyer and seller but does no buying or selling. The buyer and seller eventually might find each other without the help of the broker, but the deal goes through much more quickly if the broker is there. In the same way, a molecule that plays the role of an enzyme possesses a shape and structure that may bring together two other molecules in a cell and facilitate their forming a bond, or it may tear a molecule apart without itself being affected in the chemical reaction. Because of the enzyme, the reaction takes place relatively quickly.</p>
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Enzymes
KEY CONCEPTS
Enzymes are protein catalysts that can do the same reaction over and over.
Enzymes speed up chemical reactions by lowering the activation energy of a reaction.
The unique physical and chemical properties of the active site limit an enzyme’s activity to specific substrates and reactions.
Living systems are shaped by an enormous variety of biochemical reactions, nearly all of which are mediated by a series of remarkable biological catalysts known as enzymes.
Enzymes are Protein Catalysts
Enzymes are a special category of proteins found in all living organisms. In fact, most cells contain hundreds of enzymes, and cells are constantly making proteins, many of which are enzymes. Enzymes are catalysts—substances that speed up chemical reactions and remain unchanged by the reaction they facilitate. Like all catalysts, enzymes increase the rates of chemical reactions by lowering the amount of energy required to start the reaction. Enzymes accomplish this feat through various mechanisms that depend on the arrangement of amino acid R groups in the enzyme’s active site, the region of the enzyme where catalysis occurs.
Enzymes illustrate the importance of shape in determining how chemical reactions take place among large molecules. Each large molecule has places on it, atoms or small groups of atoms, that are reactive—that is, where chemical bonding can take place. However, these areas are relatively small compared to the large, convoluted shape of the molecules. In order for two or more molecules to interact, their respective reactive areas have to come into contact. More precisely, the atoms whose electrons will eventually form the bonds must be brought close enough together for the electrons to interact. This proximity is unlikely to happen at random, but can happen quickly if a catalyst is involved.
Enzymes Lower Activation Energy
A chemical reaction takes place when the bonding in one or more reactant molecules are changed to yield one or more products. Many chemical reactions require an input of energy from the surroundings to begin. Even if the reaction is a favorable one (one in which the products are at a lower energy state than the reactants), there is usually some amount of energy needed to initiate the process. The energy required to start such a reaction is called activation energy (Figure 2-29).
Enzymes Act on Specific Substrates
How does an enzyme know which molecule(s) it needs to react with and avoid catalyzing a chemical reaction on the wrong molecule(s)? The answer is substrate specificity. A substrate is a molecule that an enzyme will bind preferentially to any other molecule, and each enzyme is specific for that substrate—it won’t react with molecules that are not its substrate. Enzymes have an active site, which serves as the binding platform for its specific substrate(s) and acts as the site of the chemical reaction (Fig. 2-30 a).
Enzymes are Affected by their Environment
Enzymes are proteins and their structure determines their function. It’s not surprising, then, that anything that would impact protein structure would also impact enzyme activity. For example, changes in pH or temperature can drastically impact enzyme activity.
Each enzyme has an optimal environment in which it will have its highest activity, and it is usually similar to the environment for which it is adapted. For example, digestive enzymes in the stomach are optimally active at very low pH because this is the environment in which they function. The closer an environment is to the optimal environment for an enzyme, the more active it will be, and the further from optimal the environment, the less active the enzyme will be.
For example, if an enzyme has an optimal pH of 5.5 and we have the choice between an environment of pH 5.2 and 6.3, the pH 5.2 environment is most likely to yield the highest activity because it is closest to the optimal pH. Similarly, if the optimal temperature is 95°C (almost boiling), then an environment with temperature 87° will yield higher activity than 37°C. Such is the case for enzymes from extreme bacteria that live in geysers and ocean vents - their enzymes have adapted to work well under those extreme temperatures and are much less active at more moderate temperatures.
Another important factor in enzyme activity is the amount of substrate present in the enzyme’s environment. The more substrate the enzyme has available the more active it will be. Thus, there are several ways to increase (or decrease) enzyme activity by changing its environment. For optimal activity, the enzyme needs to be as close to its optimal temperature and pH as possible with plenty of substrate around.
Enzymes in Pathways
Reactions that are catalyzed by enzymes are generally shown in a standard way. The action of the enzyme is represented by an arrow with the enzyme name written either inside or next to the arrow. The name or structure of the substrate(s) will be shown at the beginning of arrow and the product(s) will be shown at the end of the arrow (Figure 2-33).
Enzyme Regulation
KEY CONCEPTS
Phosphorylation and dephosphorylation of an enzyme can control its activity by shifting the equilibrium between more active and less active conformations.
Enzymes can be inhibited by competitive or noncompetitive inhibitors. Feedback inhibition is noncompetitive inhibition of an enzyme in a pathway by the product of that pathway.
Pharmaceutical drugs can be used to modulate enzyme activity by inhibiting or supplementation to treat diseases or alleviate symptoms.
An organism must be able to control the catalytic activities of its many enzymes so that it can coordinate its numerous metabolic processes, respond to changes in its environment, and grow and differentiate, all in an orderly manner. There are two ways that this may occur:
Control of enzyme availability. The amount of a given enzyme in a cell depends on both its rate of synthesis and its rate of degradation. Each of these rates is directly controlled by the cell and is subject to dramatic changes over time spans of minutes (in bacteria) to hours (in higher organisms).
Control of enzyme activity. An enzyme’s activity can be inhibited by the accumulation of product and by the presence of other types of inhibitors. In fact, an enzyme’s catalytic activity can be modulated—either negatively or positively—through structural alterations that influence the enzyme’s substrate-binding affinity or reaction rate.
In the following sections, we discuss the control of enzyme activity by covalent modification and inhibition.
Control by Covalent Modification Usually Involves Protein Phosphorylation
Many enzymes are subject to control by protein modification. By far, the most common such modification is phosphorylation and dephosphorylation (the attachment and removal of a phosphate group) of a polar amino acid residue. A phosphate group consists of a phosphate atom connected to four oxygen atoms, and it has an overall charge of (-2) (see bottom of Figure 2-34 part A). The phosphate group, with its double negative charge (a property not shared with naturally occurring amino acid residues) and its covalent attachment to a protein, can induce dramatic conformational changes in the protein structure. These changes in structural conformation are what regulate the enzyme activity.
Enzyme Inhibition
No organism can afford to allow continual maximum activity of all its enzymes. Not only is this a waste of materials and energy, but it also may allow harmful quantities of compounds to accumulate, while others are lacking. Therefore, the cell must have ways to inhibit enzyme activity in order to slow or even stop its rate. There are two common kinds of inhibitors: competitive inhibitors and noncompetitive inhibitors.
A competitive inhibitor is usually a molecule similar in structure to a substrate that can bind to an enzyme’s active site even though the molecule is unable to react. This non-substrate molecule competes with the substrate for the active site (Fig. 2-35).
Clinical Connection: Many Drugs Target Enzymes
The cell has a wide variety of enzymes, all part of various pathways that contribute to the overall function of the cell. The balance of enzyme activity is vital to the health of the organism, and mutations in enzymes can have clinical consequences. For example, the reduced or absent activity of the enzyme phenylalanine hydroxylase results in a build up of the amino acid phenylalanine in the body, leading to the symptoms of phenylketonuria (PKU).
Pharmaceutical drugs can affect enzyme activity in order to treat diseases, or at least alleviate their symptoms. This can be done with two different strategies: inhibition of enzyme activity or supplementation to increase enzyme activity.
An example of supplementation is the treatment of Parkinson’s disease with large doses of L-DOPA, the precursor to dopamine in the body. The protein aggregation associated with Parkinson’s disease substantially lowers dopamine production in the nervous system, leading to the symptoms of Parkinson’s disease. By supplementing with large amounts of L-DOPA, the enzyme that makes dopamine (DOPA decarboxylase), has large amounts of substrate to act on, and thereby increases its activity. The result is larger amounts of dopamine in the body that alleviate many of the symptoms of Parkinson’s disease.
lesson 2 review
Enzymes are protein catalysts that perform most of the chemical reactions that take place in a cell. Like all catalysts, enzymes speed up the reaction by lowering activation energy (the energy needed to get the reaction started), but they are not consumed by the reaction themselves. Instead, they can be “recycled” and perform the same reaction again and again.
Enzymes are specific in the reaction they catalyze as well as the molecules they act on. These molecules are known as the enzyme’s substrate, and each enzyme is specific for that substrate. The specificity is derived from the structure and chemical nature of an enzyme’s active site, the place on the enzyme where the substrate will bind and the reaction will take place. Substrates are recognized by their complementarity in both shape and functional groups. For example, an active site with a large hydrophobic pocket will require a substrate with a large hydrophobic area. Similarly, an active site with positively charged R groups will bind substrates with negatively charged areas. Many enzymes undergo an induced fit by adjusting their active site conformation slightly as the substrate binds to improve the fit.
In order to control and coordinate the action of the many enzymes in a cell, enzymes are regulated. This regulation happens at two levels: First, the amount of enzyme made by the ribosomes can be changed depending on the expression of the enzyme gene. Second, the activity of the existing enzymes can be modulated. This is done by protein modification and/or inhibitors. The most common protein modification is phosphorylation—the addition of a phosphate to a protein. The phosphate group induces conformational changes in the enzyme that can increase or decrease its activity, and this regulation allows the cell to effectively respond to its environment. Other molecules, such as lipids and carbohydrates, can also be used in protein modification and regulation.
Enzymes can also be controlled by inhibition. In the cell, this is often done through feedback inhibition, in which the final product of a pathway can inhibit the action of an enzyme earlier in the pathway in order to stop the production of the final product. Pharmaceutical drugs are also inhibitors that can be used to control an enzyme activity for the purpose of treating a disease or alleviating the symptoms of a condition. Inhibitors usually fall into one of two categories. Competitive inhibitors bind to the active site of the enzyme and compete with the substrate, thus lowering the amount of substrate that is converted to product by the enzyme. Noncompetitive inhibitors do not bind to the active site, but instead bind allosteric sites elsewhere on the enzyme and affect its conformation such that the reaction slows or no longer takes place.
Pharmaceutical drugs often target enzymes in order to alleviate symptoms or treat disease. Donepezil, the treatment prescribed for Deedra’s father to improve cognitive function, is such a drug.
How well do you understand the Lesson 2 material? Click on the Module 2 Check Your Understanding: Enzymes to take the short self-quiz. When you are finished, navigate back to this lesson using the breadcrumbs at the top, to continue to the Case Study Review and Reflection.
