6: Metabolism Flashcards
Energy and Metabolism, Potential, Kinetic, Free, and Activation Energy, the Laws of Thermodynamics, ATP: Adenosine Triphosphate, Enzymes
1
Q
What are anabolic pathways?
A
Pathways that require an input of energy to synthesize complex molecules from simpler ones. (Also, anabolism).
2
Q
What is bioenergetics?
A
The study of energy flowing through living systems.
3
Q
What are catabolic pathways?
A
Pathways in which complex molecules are broken down into simpler ones. (Also, catabolism).
4
Q
What is metabolism?
A
All the chemical reactions that take place inside cells, including anabolism and catabolism.
5
Q
What are the benefits of sugar to living organisms?
A
Living things consume sugar as a major energy source, because sugar molecules have a great deal of energy stored within their bonds.
6
Q
What is the formula for the synthesis and catabolism of glucose?
A
6CO2 + 6H2O + (energy) ⇐⇒ C6H12O6 + 6O2
7
Q
What is the primary producer of sugar?
A
Carbohydrates that are consumed have their origins in photosynthesizing organisms like plants. During photosynthesis, plants use the energy of sunlight to convert carbon dioxide gas (CO2) into sugar molecules, like glucose (C6H12O6). Because this process involves synthesizing a larger, energy-storing molecule, it requires an input of energy to proceed.
8
Q
What is the source of energy for the sugar production?
A
During the chemical reactions of photosynthesis, energy is provided in the form of a very high-energy molecule called ATP, or adenosine triphosphate, which is the primary energy currency of all cells used to perform immediate work.
9
Q
How is sugar stored in living organisms?
A
The sugar (glucose) is stored as starch or glycogen. Energy-storing polymers like these are broken down into glucose to supply molecules of ATP.
10
Q
How is solar energy used to produce glucose?
A
Solar energy is required to synthesize a molecule of glucose during the reactions of photosynthesis. In photosynthesis, light energy from the sun is initially transformed into chemical energy that is temporally stored in the energy carrier molecules ATP and NADPH (nicotinamide adenine dinucleotide phosphate). The stored energy in ATP and NADPH is then used later in photosynthesis to build one molecule of glucose from six molecules of CO2. Glucose molecules can also be combined with and converted into other types of sugars.
11
Q
What happens when sugars are consumed?
A
When sugars are consumed, molecules of glucose eventually make their way into each living cell of the organism. Inside the cell, each sugar molecule is broken down through a complex series of chemical reactions. The goal of these reactions is to harvest the energy stored inside the sugar molecules. The harvested energy is used to make high-energy ATP molecules, which can be used to perform work, powering many chemical reactions in the cell.
12
Q
How much energy is required to synthesize glucose?
A
Under ideal conditions, the amount of energy needed to make one molecule of glucose from six molecules of carbon dioxide during photosynthesis is 18 molecules of ATP and 12 molecules of NADPH (each one of which is energetically equivalent to three molecules of ATP), or a total of 54 molecule equivalents required for the synthesis of one molecule of glucose.
13
Q
What is a metabolic pathway?
A
A metabolic pathway is a series of interconnected biochemical reactions that convert a substrate molecule or molecules, step-by-step, through a series of metabolic intermediates, eventually yielding a final product or products.
14
Q
Which types of organisms perform the most photosynthesis?
A
The majority of global photosynthesis is done by planktonic algae.
15
Q
How does photosynthesis enable cellular respiration?
A
The by-product of photosynthesis is oxygen, required by some cells to carry out cellular respiration. During cellular respiration, oxygen aids in the catabolic breakdown of carbon compounds, like carbohydrates. Among the products of this catabolism are CO2 and ATP. In addition, some eukaryotes perform catabolic processes without oxygen (fermentation); that is, they perform or use anaerobic metabolism.
16
Q
How did metabolism evolve?
A
Organisms probably evolved anaerobic metabolism to survive (living organisms came into existence about 3.8 billion years ago, when the atmosphere lacked oxygen). Despite the differences between organisms and the complexity of metabolism, researchers have found that all branches of life share some of the same metabolic pathways, suggesting that all organisms evolved from the same ancient common ancestor. Evidence indicates that over time, the pathways diverged, adding specialized enzymes to allow organisms to better adapt to their environment, thus increasing their chance to survive. However, the underlying principle remains that all organisms must harvest energy from their environment and convert it to ATP to carry out cellular functions.
17
Q
What are some examples of anabolic pathways?
A
Synthesizing sugar from CO2 is one example. Other examples are the synthesis of large proteins from amino acid building blocks, and the synthesis of new DNA strands from nucleic acid building blocks.
18
Q
How much ATP can be produced through the catabolism of glucose?
A
A single molecule of glucose can store enough energy to make 36 to 38 molecules of ATP.
19
Q
What other types of molecules besides carbohydrates are used to produce ATP?
A
Other energy-storing molecules, such as fats, are also broken down through similar catabolic reactions to release energy and make ATP.
20
Q
How do proteins facilitate metabolic pathways?
A
The chemical reactions of metabolic pathways don’t take place spontaneously. Each reaction step is facilitated, or catalyzed, by a protein called an enzyme. Enzymes are important for catalyzing all types of biological reactions—those that require energy as well as those that release energy.
21
Q
What is activation energy?
A
The energy necessary for reactions to occur.
22
Q
What is chemical energy?
A
The potential energy in chemical bonds that is released when those bonds are broken.
23
Q
What are endergonic reactions?
A
Chemical reactions that require energy input.
24
Q
What is enthalpy?
A
The total energy of a system.
25
What are exergonic reactions?
Chemical reactions that release free energy.
26
What is free energy?
Gibbs free energy is the usable energy, or energy that is available to do work.
27
What is heat energy?
The total bond energy of reactants or products in a chemical reaction.
28
What is kinetic energy?
A type of energy associated with objects or particles in motion.
29
What is potential energy?
A type of energy that has the potential to do work; stored energy.
30
What is a transition state?
A high-energy, unstable state (an intermediate form between the substrate and the product) occurring during a chemical reaction.
31
What is energy?
Energy is defined as the ability to do work.
32
Why is free energy called Gibbs free energy?
Free energy is called Gibbs free energy (abbreviated with the letter G) after Josiah Willard Gibbs, the scientist who developed the measurement.
33
How does Gibbs free energy take into account the second law of thermodynamics?
Gibbs free energy specifically refers to the energy associated with a chemical reaction that is available after entropy is accounted for. In other words, Gibbs free energy is usable energy, or energy that is available to do work.
34
How does free energy change in a chemical reaction?
Every chemical reaction involves a change in free energy, called delta G (∆G). The change in free energy can be calculated for any system that undergoes such a change, such as a chemical reaction. To calculate ∆G, subtract the amount of energy lost to entropy (denoted as ∆S) from the total energy change of the system. This total energy change in the system is called enthalpy and is denoted as ∆H. The formula for calculating ∆G is as follows, where the symbol T refers to absolute temperature in Kelvin (degrees Celsius + 273):
ΔG = ΔH − TΔS
35
How is the standard free energy change of a chemical reaction expressed?
The standard free energy change of a chemical reaction is expressed as an amount of energy per mole of the reaction product (either in kilojoules or kilocalories, kJ/mol or kcal/mol; 1 kJ = 0.239 kcal) under standard pH, temperature, and pressure conditions.
36
What is standard pH, temperature, and pressure?
Standard pH, temperature, and pressure conditions are generally calculated at pH 7.0 in biological systems, 25 degrees Celsius, and 100 kilopascals (1 atm pressure), respectively.
37
What must be taken into account when calculating the free energy change of a chemical reaction in a cellular environment?
Cellular conditions vary considerably from the standard conditions, and so standard calculated ∆G values for biological reactions will be different inside the cell.
38
What is the free energy change of reactions that release energy?
Reactions that release energy have a ∆G \< 0. A negative ∆G also means that the products of the reaction have less free energy than the reactants, because they gave off some free energy during the reaction. Reactions that have a negative ∆G and consequently release free energy are called exergonic reactions. These reactions are also referred to as spontaneous reactions, because they can occur without the addition of energy into the system.
39
What is the free energy change of a reaction that stores energy?
If a chemical reaction requires an input of energy rather than releasing energy, then the ∆G for that reaction will be a positive value. In this case, the products have more free energy than the reactants. Thus, the products of these reactions can be thought of as energy-storing molecules. These chemical reactions are called endergonic reactions, and they are non-spontaneous. An endergonic reaction will not take place on its own without the addition of free energy.
40
How does reaction reversibility factor into free energy change?
Most chemical reactions are reversible. They can proceed in both directions, releasing energy into their environment in one direction, and absorbing it from the environment in the other direction. The same is true for the chemical reactions involved in cell metabolism, such as the breaking down and building up of proteins into and from individual amino acids, respectively.
41
Why do living systems never achieve a state of equilibrium?
Reactants within a closed system will undergo chemical reactions in both directions until a state of equilibrium is reached. This state of equilibrium is one of the lowest possible free energy and a state of maximal entropy. Energy must be put into the system to push the reactants and products away from a state of equilibrium. Either reactants or products must be added, removed, or changed. If a cell were a closed system, its chemical reactions would reach equilibrium, and it would die because there would be insufficient free energy left to perform the work needed to maintain life. In a living cell, chemical reactions are constantly moving towards equilibrium, but never reach it. This is because a living cell is an open system. Materials pass in and out, the cell recycles the products of certain chemical reactions into other reactions, and chemical equilibrium is never reached. In this way, living organisms are in a constant energy-requiring, uphill battle against equilibrium and entropy. This constant supply of energy ultimately comes from sunlight, which is used to produce nutrients in the process of photosynthesis.
42
How is energy used to catalyze a chemical reaction?
Even exergonic reactions require a small amount of energy input to get going before they can proceed with their energy-releasing steps. These reactions have a net release of energy, but still require some energy in the beginning. This small amount of energy input necessary for all chemical reactions to occur is called the activation energy (or free energy of activation) and is abbreviated EA.
43
Why is activation energy required to start a reaction?
During chemical reactions, certain chemical bonds are broken and new ones are formed. Since these are energy-storing bonds, they release energy when broken. However, to get them into a state that allows the bonds to break, the molecule must be somewhat contorted. A small energy input is required to achieve this contorted state. This contorted state is called the transition state.
44
What is the energy of a transition state?
The transition state is a high-energy, unstable state. For this reason, reactant molecules don’t last long in their transition state, but very quickly proceed to the next steps of the chemical reaction. Free energy diagrams illustrate the energy profiles for a given reaction. The transition state of the reaction exists at a higher energy state than the reactants, and thus, EA is always positive.
45
Where does the activation energy required by chemical reactants come from?
The source of the activation energy needed to push reactions forward is typically heat energy from the surroundings. Heat energy (the total bond energy of reactants or products in a chemical reaction) speeds up the motion of molecules, increasing the frequency and force with which they collide; it also moves atoms and bonds within the molecule slightly, helping them reach their transition state. For this reason, heating up a system will cause chemical reactants within that system to react more frequently. Increasing the pressure on a system has the same effect. Once reactants have absorbed enough heat energy from their surroundings to reach the transition state, the reaction will proceed.
46
How is activation energy related to reaction rate?
The activation energy of a particular reaction determines the rate at which it will proceed. The higher the activation energy, the slower the chemical reaction will be.
47
What are some examples of activation energy and subsequent reaction speed?
The example of iron rusting illustrates an inherently slow reaction. This reaction occurs slowly over time because of its high EA. Additionally, the burning of many fuels, which is strongly exergonic, will take place at a negligible rate unless their activation energy is overcome by sufficient heat from a spark. Once they begin to burn, however, the chemical reactions release enough heat to continue the burning process, supplying the activation energy for surrounding fuel molecules.
48
What is used in addition to heat energy to increase the rate of chemical reactions in a cellular environment?
The activation energy for most cellular reactions is too high for heat energy to overcome at efficient rates. In other words, in order for important cellular reactions to occur at appreciable rates (number of reactions per unit time), their activation energies must be lowered; this is referred to as catalysis.
49
Why is reaction catalysis beneficial in cells?
Important macromolecules, such as proteins, DNA, and RNA, store considerable energy, and their breakdown is exergonic. If cellular temperatures alone provided enough heat energy for these exergonic reactions to overcome their activation barriers, the essential components of a cell would disintegrate.
50
What is entropy (S)?
The measure of randomness or disorder within a system.
51
What is heat?
The energy transferred from one system to another that is not work (energy of the motion of molecules or particles).
52
What is thermodynamics?
The study of energy and energy transfer involving physical matter.
53
In thermodynamics, what is a system and its surroundings?
The matter and its environment relevant to a particular case of energy transfer are classified as a system, and everything outside of that system is called the surroundings.
54
What are the two types of systems in thermodynamics?
There are two types of systems: open and closed. An open system is one in which energy can be transferred between the system and its surroundings. A closed system is one that cannot transfer energy to its surroundings.
55
Are biological systems open or closed?
Biological organisms are open systems. Energy is exchanged between them and their surroundings, as they consume energy-storing molecules and release energy to the environment by doing work.
56
What is the first law of thermodynamics?
The first law of thermodynamics deals with the total amount of energy in the universe. It states that this total amount of energy is constant. In other words, there has always been, and always will be, exactly the same amount of energy in the universe. Energy exists in many different forms. According to the first law of thermodynamics, energy may be transferred from place to place or transformed into different forms, but it cannot be created or destroyed.
57
What are some examples of energy transformations?
Light bulbs transform electrical energy into light energy. Gas stoves transform chemical energy from natural gas into heat energy. Plants convert the energy of sunlight into the chemical energy stored within organic molecules.
58
How is energy converted into a usable form by living organisms?
Chemical energy stored within organic molecules such as sugars and fats is transformed through a series of cellular chemical reactions into energy within molecules of ATP. Energy in ATP molecules is easily accessible to do work.
59
What are some examples of work that cells do?
Building complex molecules, transporting materials, powering the beating motion of cilia or flagella, contracting muscle fibers to create movement, reproduction.
60
What is the second law of thermodynamics?
No energy transfer is completely efficient. In every energy transfer, some amount of energy is lost in a form that is unusable. In most cases, this form is heat energy. Thermodynamically, heat energy is defined as the energy transferred from one system to another that is not doing work.
61
How is entropy related to energy?
The more energy that is lost by a system to its surroundings, the less ordered and more random the system is. Scientists refer to the measure of randomness or disorder within a system as entropy. High entropy means high disorder and low energy.
62
What are some ways in which entropy increases at the molecular level?
Two ways in which entropy increases is when chemical reactions approach a state of equilibrium and when molecules at a high concentration in one place diffuse and spread out.
63
What is the consequence of the second law of thermodynamics on universal entropy?
Living things are highly ordered, requiring constant energy input to be maintained in a state of low entropy. As living systems take in energy-storing molecules and transform them through chemical reactions, they lose some amount of usable energy in the process, because no reaction is completely efficient. They also produce waste and by-products that aren’t useful energy sources. This process increases the entropy of the system’s surroundings. Since all energy transfers result in the loss of some usable energy, the second law of thermodynamics states that every energy transfer or transformation increases the entropy of the universe. Even though living things are highly ordered and maintain a state of low entropy, the entropy of the universe in total is constantly increasing due to the loss of usable energy with each energy transfer that occurs. Essentially, living things are in a continuous uphill battle against this constant increase in universal entropy.
64
What is ATP?
Adenosine triphosphate, the cell's energy currency.
65
What is a phosphoanhydride bond?
A bond that connects phosphates in an ATP molecule.
66
What it ATP composed of?
Adenosine triphosphate is comprised of adenosine bound to three phosphate groups. Adenosine is a nucleoside consisting of the nitrogenous base adenine and a five-carbon sugar, ribose. The three phosphate groups, in order of closest to furthest from the ribose sugar, are labeled alpha, beta, and gamma.
67
Which bonds in an ATP molecule are high-energy?
Not all bonds within this molecule exist in a particularly high-energy state. Both bonds that link the phosphates are equally high-energy bonds (phosphoanhydride bonds) that, when broken, release sufficient energy to power a variety of cellular reactions and processes. These high-energy bonds are the bonds between the second and third (or beta and gamma) phosphate groups and between the first and second (alpha and beta) phosphate groups.
68
Why are phosphoanhydride bonds considered high-energy?
The reason that these bonds are considered “high-energy” is because the products of such bond breaking—adenosine diphosphate (ADP) and one inorganic phosphate group (Pi)—have considerably lower free energy than the reactants: ATP and a water molecule.
69
Why type of reaction is the catabolism of ATP into ADP?
Because this reaction takes place with the use of a water molecule, it is considered a hydrolysis reaction.
70
What is the formula for the hydrolysis of ATP?
ATP + H2O ⇐⇒ ADP + Pi + free energy
71
How much energy is released with the hydrolysis of ATP?
The calculated ∆G for the hydrolysis of one mole of ATP into ADP and Pi is −7.3 kcal/mole (−30.5 kJ/mol). Since this calculation is true under standard conditions, it would be expected that a different value exists under cellular conditions. In fact, the ∆G for the hydrolysis of one mole of ATP in a living cell is almost double the value at standard conditions: −14 kcal/mol (−57 kJ/mol).
72
What happens if an ATP molecule is not used?
ATP is a highly unstable molecule. Unless quickly used to perform work, ATP spontaneously dissociates into ADP + Pi, and the free energy released during this process is lost as heat.
73
What is energy coupling?
Cells couple the exergonic reaction of ATP hydrolysis with endergonic reactions, allowing them to proceed.
74
How does the Na+/K+ pump use energy-coupling to operate?
The sodium-potassium pump (Na+/K+ pump) drives sodium out of the cell and potassium into the cell. A large percentage of a cell’s ATP is spent powering this pump, because cellular processes bring a great deal of sodium into the cell and potassium out of the cell. The pump works constantly to stabilize cellular concentrations of sodium and potassium. In order for the pump to turn one cycle (exporting three Na+ ions and importing two K+ ions), one molecule of ATP must be hydrolyzed. When ATP is hydrolyzed, its gamma phosphate doesn’t simply float away, but is actually transferred onto the pump protein. This process of a phosphate group binding to a molecule is called phosphorylation. As with most cases of ATP hydrolysis, a phosphate from ATP is transferred onto another molecule. In a phosphorylated state, the Na+/K+ pump has more free energy and is triggered to undergo a conformational change. This change allows it to release Na+ to the outside of the cell. It then binds extracellular K+, which, through another conformational change, causes the phosphate to detach from the pump. This release of phosphate triggers the K+ to be released to the inside of the cell. Essentially, the energy released from the hydrolysis of ATP is coupled with the energy required to power the pump and transport Na+ and K+ ions. ATP performs cellular work using this basic form of energy coupling through phosphorylation.
75
Why are conformational changes used during metabolic reactions?
Often during cellular metabolic reactions, such as the synthesis and breakdown of nutrients, certain molecules must be altered slightly in their conformation to become substrates for the next step in the reaction series.
76
What is an example of conformational changes used in cellular respiration?
During the very first steps of cellular respiration, when a molecule of the sugar glucose is broken down in the process of glycolysis. In the first step of this process, ATP is required for the phosphorylation of glucose, creating a high-energy but unstable intermediate. This phosphorylation reaction powers a conformational change that allows the phosphorylated glucose molecule to be converted to the phosphorylated sugar fructose. Fructose is a necessary intermediate for glycolysis to move forward. Here, the exergonic reaction of ATP hydrolysis is coupled with the endergonic reaction of converting glucose into a phosphorylated intermediate in the pathway. Once again, the energy released by breaking a phosphate bond within ATP was used for the phosphorylation of another molecule, creating an unstable intermediate and powering an important conformational change.
77
What is an active site?
A specific region of the enzyme to which the substrate binds.
78
What is allosteric inhibition?
Inhibition by a binding event at a site different from the active site, which induces a conformational change and reduces the affinity of the enzyme for its substrate.
79
What is a coenzyme?
A small organic molecule, such as a vitamin or its derivative, which is required to enhance the activity of an enzyme.
80
What is a cofactor?
An inorganic ion, such as iron and magnesium ions, required for optimal regulation of enzyme activity.
81
What is competitive inhibition?
A type of inhibition in which the inhibitor competes with the substrate molecule by binding to the active site of the enzyme.
82
What does it mean to denature in a process?
A process that changes the natural properties of a substance.
83
What is feedback inhibition?
The effect of a product of a reaction sequence to decrease its further production by inhibiting the activity of the first enzyme in the pathway that produces it.
84
What is induced fit?
A dynamic fit between the enzyme and its substrate, in which both components modify their structures to allow for ideal binding.
85
What is a substrate?
A molecule on which the enzyme acts.
86
What is an enzyme?
A substance that helps a chemical reaction to occur is a catalyst, and the special molecules that catalyze biochemical reactions are called enzymes. Almost all enzymes are proteins, made up of chains of amino acids, and they perform the critical task of lowering the activation energies of chemical reactions inside the cell.
87
How do enzymes lower the activation energy of a chemical reaction?
Enzymes lower activation energy by binding to the reactant molecules, and holding them in such a way as to make the chemical bond-breaking and bond-forming processes take place more readily.
88
How do enzymes affect the free energy of a reaction?
Enzymes don’t change the ∆G of a reaction. In other words, they don’t change whether a reaction is exergonic (spontaneous) or endergonic. This is because they don’t change the free energy of the reactants or products. They only reduce the activation energy required to reach the transition state.
89
How many substrates may an enzyme have?
There may be one or more substrates, depending on the particular chemical reaction. In some reactions, a single-reactant substrate is broken down into multiple products. In others, two substrates may come together to create one larger molecule. Two reactants might also enter a reaction, both become modified, and leave the reaction as two products.
90
Why do enzymes have high specificity?
Since enzymes are proteins, there is a unique combination of amino acid residues (also called side chains, or R groups) within the active site. Each residue is characterized by different properties. Residues can be large or small, weakly acidic or basic, hydrophilic or hydrophobic, positively or negatively charged, or neutral. The unique combination of amino acid residues, their positions, sequences, structures, and properties, creates a very specific chemical environment within the active site. This specific environment is suited to bind, albeit briefly, to a specific chemical substrate (or substrates). Due to this jigsaw puzzle-like match between an enzyme and its substrates (which adapts to find the best fit between the transition state and the active site), enzymes are known for their specificity. The “best fit” results from the shape and the amino acid functional group’s attraction to the substrate. There is a specifically matched enzyme for each substrate and, thus, for each chemical reaction.
91
How does temperature affect enzymatic reaction rates?
It is true that increasing the environmental temperature generally increases reaction rates, enzyme-catalyzed or otherwise. However, increasing or decreasing the temperature outside of an optimal range can affect chemical bonds within the active site in such a way that they are less well suited to bind substrates. High temperatures will eventually cause enzymes, like other biological molecules, to denature, a process that changes the natural properties of a substance.
92
How does pH affect enzymatic reaction rates?
The pH of the local environment can also affect enzyme function. Active site amino acid residues have their own acidic or basic properties that are optimal for catalysis. These residues are sensitive to changes in pH that can impair the way substrate molecules bind. Enzymes are suited to function best within a certain pH range, and, as with temperature, extreme pH values (acidic or basic) of the environment can cause enzymes to denature.
93
How does the induced-fit model explain enzyme active site binding?
For many years, scientists thought that enzyme-substrate binding took place in a simple “lock-and-key” fashion. This model asserted that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view called induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild shift in the enzyme’s structure that confirms an ideal binding arrangement between the enzyme and the transition state of the substrate. This ideal binding maximizes the enzyme’s ability to catalyze its reaction.
94
What is an enzyme-substrate complex?
When an enzyme binds its substrate, an enzyme-substrate complex is formed. This complex lowers the activation energy of the reaction and promotes its rapid progression in one of many ways.
95
How do enzymes promote catalysis through orientation in their active sites?
Enzymes promote chemical reactions that involve more than one substrate by bringing the substrates together in an optimal orientation. The appropriate region (atoms and bonds) of one molecule is juxtaposed to the appropriate region of the other molecule with which it must react. The enzyme-substrate complex can lower the activation energy by contorting substrate molecules in such a way as to facilitate bond-breaking, helping to reach the transition state.
96
How do enzymes promote catalysis through the environment the active site provides?
Enzymes may create an optimal environment within the active site for the reaction to occur. Certain chemical reactions might proceed best in a slightly acidic or non-polar environment. The chemical properties that emerge from the particular arrangement of amino acid residues within an active site create the perfect environment for an enzyme’s specific substrates to react. The amino acid residues can provide certain ions or chemical groups that actually form covalent bonds with substrate molecules as a necessary step of the reaction process.
97
What is the impact of catalysis on enzymes?
The enzyme will always return to its original state at the completion of the reaction. Enzymes remain ultimately unchanged by the reactions they catalyze. After an enzyme is done catalyzing a reaction, it releases its product(s).
98
What are some ways in which enzyme activity changes over time and place?
Cellular needs and conditions vary from cell to cell, and change within individual cells over time. The required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and functionality of different enzymes.
99
How do enzymes regulate reaction rates?
Since the rates of biochemical reactions are controlled by activation energy, and enzymes lower and determine activation energies for chemical reactions, the relative amounts and functioning of the variety of enzymes within a cell ultimately determine which reactions will proceed and at which rates. This determination is tightly controlled.
100
How is enzyme activity regulated?
In certain cellular environments, enzyme activity is partly controlled by environmental factors, like pH and temperature. There are other mechanisms through which cells control the activity of enzymes and determine the rates at which various biochemical reactions will occur. Enzymes can be regulated in ways that either promote or reduce their activity. There are many different kinds of molecules that inhibit or promote enzyme function, and various mechanisms exist for doing so.
101
How can competitive inhibition be used to regulate enzyme activity?
In some cases of enzyme inhibition, for example, an inhibitor molecule is similar enough to a substrate that it can bind to the active site and simply block the substrate from binding. When this happens, the enzyme is inhibited through competitive inhibition, because an inhibitor molecule competes with the substrate for active site binding. On the other hand, in noncompetitive inhibition, an inhibitor molecule binds to the enzyme in a location other than an allosteric site and still manages to block substrate binding to the active site.
102
How can allosteric inhibition and activation be used to regulate enzyme activity?
Some inhibitor molecules bind to enzymes in a location where their binding induces a conformational change that reduces the affinity of the enzyme for its substrate. This type of inhibition is called allosteric inhibition. Most allosterically regulated enzymes are made up of more than one polypeptide, meaning that they have more than one protein subunit. When an allosteric inhibitor binds to an enzyme, all active sites on the protein subunits are changed slightly such that they bind their substrates with less efficiency. There are allosteric activators as well as inhibitors. Allosteric activators bind to locations on an enzyme away from the active site, inducing a conformational change that increases the affinity of the enzyme’s active site(s) for its substrate(s).
103
How is the understanding of enzymes used in the design of pharmaceutical drugs?
Understanding how enzymes work and how they can be regulated is a key principle behind the development of many of the pharmaceutical drugs on the market today. Biologists working in this field collaborate with other scientists, usually chemists, to design drugs.
104
How do statins work?
Statins, which is the name given to the class of drugs that reduces cholesterol levels, are essentially inhibitors of the enzyme HMG-CoA reductase. HMG-CoA reductase is the enzyme that synthesizes cholesterol from lipids in the body. By inhibiting this enzyme, the levels of cholesterol synthesized in the body can be reduced.
105
How does acetaminophen work?
Acetaminophen, popularly marketed under the brand name Tylenol, is an inhibitor of the enzyme cyclooxygenase. While it is effective in providing relief from fever and inflammation (pain), its mechanism of action is still not completely understood.
106
How are drugs developed?
One of the first challenges in drug development is identifying the specific molecule that the drug is intended to target. Drug targets are identified through painstaking research in the laboratory. Identifying the target alone is not sufficient; scientists also need to know how the target acts inside the cell and which reactions go awry in the case of disease. Once the target and the pathway are identified, then the actual process of drug design begins. During this stage, chemists and biologists work together to design and synthesize molecules that can either block or activate a particular reaction. However, this is only the beginning: both if and when a drug prototype is successful in performing its function, then it must undergo many tests from in vitro experiments to clinical trials before it can get FDA approval to be on the market.
107
How do cofactors and coenzymes promote enzyme activity?
Many enzymes don’t work optimally, or even at all, unless bound to other specific non-protein helper molecules, either temporarily through ionic or hydrogen bonds or permanently through stronger covalent bonds. Two types of helper molecules are cofactors and coenzymes. Binding to these molecules promotes optimal conformation and function for their respective enzymes. Enzyme function is, in part, regulated by an abundance of various cofactors and coenzymes, which are supplied primarily by the diets of most organisms.
108
What are some examples of cofactors?
Cofactors are inorganic ions such as iron (Fe++) and magnesium (Mg++). One example of an enzyme that requires a metal ion as a cofactor is the enzyme that builds DNA molecules, DNA polymerase, which requires bound zinc ion (Zn++) to function.
109
What are some examples of coenzymes?
The most common sources of coenzymes are dietary vitamins. Some vitamins are precursors to coenzymes and others act directly as coenzymes. Vitamin C is a coenzyme for multiple enzymes that take part in building the important connective tissue component, collagen.
110
What is an example of an enzyme that requires both cofactors and coenzymes?
An important step in the breakdown of glucose to yield energy is catalysis by a multi-enzyme complex called pyruvate dehydrogenase. Pyruvate dehydrogenase is a complex of several enzymes that actually requires one cofactor (a magnesium ion) and five different organic coenzymes to catalyze its specific chemical reaction.
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How are enzymes compartmentalized?
In eukaryotic cells, molecules such as enzymes are usually compartmentalized into different organelles. This allows for yet another level of regulation of enzyme activity. Enzymes required only for certain cellular processes can be housed separately along with their substrates, allowing for more efficient chemical reactions.
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What are some examples of enzyme regulation by compartmentalization?
Examples of enzyme regulation based on location and proximity include the enzymes involved in the latter stages of cellular respiration, which take place exclusively in the mitochondria, and the enzymes involved in the digestion of cellular debris and foreign materials, located within lysosomes.
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What is the source of the molecules that regulate enzyme activity?
A wide variety of molecules can perform allosteric modulation, and competitive and noncompetitive inhibition. Some of these molecules include pharmaceutical and non-pharmaceutical drugs, toxins, and poisons from the environment. Perhaps the most relevant sources of enzyme regulatory molecules, with respect to cellular metabolism, are the products of the cellular metabolic reactions themselves.
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How is feedback inhibition used to regulate enzyme activity?
Feedback inhibition involves the use of a reaction product to regulate its own further production. The cell responds to the abundance of specific products by slowing down production during anabolic or catabolic reactions. Such reaction products may inhibit the enzymes that catalyzed their production through the various mechanisms of enzyme regulation.
115
How is the production of proteins and nucleic acids regulated?
The production of both amino acids and nucleotides is controlled through feedback inhibition.
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How does ATP regulate enzyme activity?
ATP is an allosteric regulator of some of the enzymes involved in the catabolic breakdown of sugar, the process that produces ATP. In this way, when ATP is abundant, the cell can prevent its further production. Because ATP is an unstable molecule that can spontaneously dissociate into ADP, if too much ATP were present in a cell, much of it would go to waste. On the other hand, ADP serves as a positive allosteric regulator (an allosteric activator) for some of the same enzymes that are inhibited by ATP. Thus, when relative levels of ADP are high compared to ATP, the cell is triggered to produce more ATP through the catabolism of sugar.
