The following is a comprehensive list of essay questions that have been asked on past AP exams. The questions are organized according to units.
Unit 1 (Basic Chemistry and Water)
1. The unique properties (characteristics) of water make life possible on Earth. Select three properties of water and:
- for each property, identify and define the property and explain it in terms of the physical/chemical nature of water.
- for each property, describe one example of how the property affects the functioning of living organisms.
Unit 2 (Organic Chemistry, Biochemistry, and Metabolism)
2. Describe the chemical composition and configuration of enzymes and discuss the factors that modify enzyme structure and/or function.
3. After an enzyme is mixed with its substrate, the amount of product formed is determined at 10-second intervals for 1 minute. Data from this experiment are shown below:
- What is the initial rate of this enzymatic reaction?
- What is the rate after 50 seconds? Why is it different from the initial rate?
- What would be the effect on product formation if the enzyme where heated to a temperature of 100° C for 10 minutes before repeating the experiment? Why?
- How might altering the substrate concentration affect the rate of the reaction? Why?
- How might altering the pH affect the rate of the reaction? Why?
|Product formed (mg)|
Draw a graph of these data and answer the following questions.
4. Enzymes are biological catalysts.
- Relate the chemical structure of an enzyme to its specificity and catalytic activity.
- Design a quantitative experiment to investigate the influence of pH or temperature on the activity of an enzyme.
- Describe what information concerning the structure of an enzyme could be inferred from your experiments.
Unit 3 (Cell Structure and Function, Cell division)
5. Describe the fluid-mosaic model of a plasma membrane. Discuss the role of the membrane in the movement of materials through it by each of the following processes:
- Active transport
- Passive transport
6. Describe the structure of a eukaryotic plant cell. Indicate the ways in which a nonphotosynthetic prokaryotic cell would differ in structure from this generalized eukaryotic plant cell.
7. Discuss the process of cell division in animals. Include a description of mitosis and cytokinesis, and of the other phases of the cell cycle. Do Not include meiosis.
8. A laboratory assistant prepared solution of 0.8 M, 0.6 M, 0.4 M, and 0.2 M sucrose, but forgot to label them. After realizing the error, the assistant randomly labeled the flasks containing these four unknown solutions as flask A, flask B, flask C, and flask D.
Design an experiment, based on the principles of diffusion and osmosis, that the assistant could use to determine which of the flasks contains each of the four unknown solutions. Include in your answer (a) a description of how you would set up and perform the experiment: (b) the results you would expect from your experiments: and (c) an explanation of those results based on the principles involved. (Be sure to clearly state the principles addressed in your discussion.)
9. Cells transport substances across their membranes. Choose THREE of the following four types of cellular transport.
- Active Transport
- Facilitated Diffusion
For each of the three transport types you choose,
- Describe the transport process and explain how the organization of cell membranes functions in the movement of specific molecules across membranes; and
- Explain the significance of each type of transport to a specific cell (you may use difference cell types as examples.)
Unit 4 (Photosynthesis and Cellular Respiration)
10. Describe the similarities and differences between the biochemical pathways of aerobic respiration and photosynthesis in eukaryotic cells. Include in your discussion the major reactions, the end products, and energy transfers.
11. The rate of photosynthesis may vary with changes that occur in environmental temperature, wavelength of light, and light intensity. Using a photosynthetic organism of your choice, choose only ONE of the three variables (temperature, wavelength of light, or light intensity) and for this variable
- design a scientific experiment to determine the effect of the variable on the rate of photosynthesis for the organism;
- explain how you would measure the rate of photosynthesis in your experiment;
- describe the results you would expect. Explain why you would expect these results.
12. Describe the light reactions of photosynthesis and, for both a C3 and a C4 plant, trace the path of a carbon dioxide molecule from the point at which it enters a plant to its incorporation into a glucose molecule. Include leaf anatomy and biochemical pathways in your discussion of each type of plant.
13. Explain what occurs during the Krebs (citric acid) cycle and electron transport by describing the following:
- The location of the Krebs cycle and electron transport chain in mitochondria.
- The cyclic nature of the reactions in the Krebs cycle.
- The production of ATP and reduced coenzymes during the cycle.
- The chemiosmotic production of ATP during electron transport.
14. Membranes are important structural features of cells.
- Describe how membrane structure is related to the transport of materials across the membrane.
- Describe the role of membranes in the synthesis of ATP in either cellular respiration or photosynthesis.
15. Energy transfer occurs in all cellular activities. For 3 of the following 5 processes involving energy transfer, explain how each functions in the cell and give an example. Explain how ATP is involved in each example you choose.
- cellular movement
- active transport
- synthesis of molecules
16. The results below are measurements of cumulative oxygen consumption by germinating and dry seeds. Gas volume measurements were corrected for changes in temperature and pressure.
- Using the graph paper provided, plot the results for the germinating seeds at 22° C and at 10° C.
- Calculate function the rate of oxygen consumption for the germinating seeds at 22° C, using the time interval between 10 and 20 minutes.
- Account for the differences in oxygen consumption observed between:
- germinating seeds at 22° C and at 10° C
- germinating seeds and dry seeds
- Describe the essential features of an experimental apparatus that could be used to measure oxygen consumption by a small organism. Explain why each of these features is necessary.
Cumulative Oxygen Consumed (mL)
22° C Germinating Seeds
10° C Germinating Seeds
Unit 5 (Meiosis, Mendelian Genetics, DNA Replication)
17. State the conclusions reached by Mendel in his work on the inheritance of characteristics. Explain how each of the following deviates from these conclusions.
- Autosomal linkage.
- Sex-linked (X-linked) inheritance.
- Polygenic (multiple-gene) inheritance.
18. Experiments by the following scientists provided critical information concerning DNA. Describe each classical experiment and indicate how it provided evidence for the chemical nature of the gene.
- Hershey and Chase- bacteriophage replication
- Griffith and Avery, MacLeod and McCarty- bacterial transformation
- Meselson and Stahl- DNA replication in bacteria
19. Discuss Mendel’s laws of segregation and independent assortment. Explain how the events of meiosis I account for the observations that led Mendel to formulate these laws.
20. An organism is heterozygous at two genetic loci on different chromosomes.
- Explain how these alleles are transmitted by the process of mitosis to daughter cells.
- Explain how these alleles are distributed by the process of meiosis to gametes.
- Explain how the behavior of these two pairs of homologous chromosomes during meiosis provides the physical basis for Mendel’s two laws of inheritance.
Labeled diagrams that are explained in your answer may be useful.
Unit 6 (Protein Synthesis, Gene Expression, DNA Technology)
21. A portion of specific DNA molecule consists of the following sequence of nucleotide triplets.
TAC GAA CTT GGG TCC
This DNA sequence codes for the following short polypeptide.
methionine – leucine – glutamic acid – proline – arginine
Describe the steps in the synthesis of this polypeptide. What would be the effect of a deletion or an addition in one of the DNA nucleotides? What would be the effects of a substitution in one of the nucleotides?
22. Describe the operon hypothesis and discuss how it explains the control of messenger RNA production and the regulation of protein synthesis in bacterial cells.
23. Scientists seeking to determine which molecule is responsible for the transmission of characteristics from one generation to the next knew that the molecule must (1) copy itself precisely, (2) be stable but able to be changed, and (3) be complex enough to determine the organism’s phenotype.
- Explain how DNA meets each of the three criteria stated above.
- Select one of the criteria stated above and describe experimental evidence used to determine that DNA is the hereditary material.
24. Describe the biochemical composition, structure, and replication of DNA. Discuss how recombinant DNA techniques may be used to correct a point mutation.
25. Describe the production and processing of a protein that will be exported from a eukaryotic cell. Begin with the separation of the messenger RNA from the DNA template and end with the release of the protein at the plasma membrane.
26. Describe the steps of protein synthesis, beginning with the attachment of a messenger RNA molecule to the small subunit of a ribosome and ending generalized with the release of the polypeptide from the ribosome. Include in your answer a discussion of how the different types of RNA function in this process.
27. The diagram below shows a segment of DNA with a total length of 4,900 base pairs. The arrows indicate reaction sites for two restriction enzymes (enzyme X and enzyme Y).
- Explain how the principles of gel electrophoresis allow for the separation of DNA fragments.
- Describe the results you would expect from the electrophoresis separation of fragments from the following treatments of the DNA segment above. Assume that the digestions occurred under appropriate conditions and went to completion.
- DNA digested with only enzyme X
- DNA digested with only enzyme Y
- DNA digested with enzyme X and enzyme Y combined
- Undigested DNA
- Explain both of the following.
- The mechanism of action of restriction enzymes.
- The different results you would expect if a mutation occurred at the recognition site for enzyme Y.
28. By using the techniques of genetic engineering, scientists are able to modify genetic materials so that a particular gene of interest from one cell can be incorporated into a different cell.
- Describe a procedure by which this can be done.
- Explain the purpose of each step of your procedure.
- Describe how you could determine whether the gene was successfully incorporated.
- Describe an example of how gene transfer and incorporation have been used in biomedical or commercial applications.
29. Assume that a particular genetic condition in a mammalian species causes an inability to digest starch. This disorder occurs with equal frequency in males and females. In most cases, neither parent of affected offspring has the condition.
- Describe the most probable pattern of inheritance for this condition. Explain your reasoning. Include in your discussion a sample cross(es) sufficient to verify your proposed pattern.
- Explain how a mutation could cause this inability to digest starch.
- Describe how modern techniques of molecular biology could be used to determine whether the mutant allele is present in a given individual.
Unit 7 (Evolution, Population Genetics, Speciation)
29. Describe the special relationship between the two terms in each of the following pairs.
- Convergent evolution of organisms and Australia.
- Blood groups and genetic drift.
- Birds of prey and DDT.
30. Describe the modern theory of evolution and discuss how it is supported by evidence from two of the following areas.
- population genetics
- molecular biology
- comparative anatomy and embryology
31. Describe the process of speciation. Include in your discussion the factors that may contribute to the maintenance of genetic isolation.
32. Do the following with reference to the Hardy-Weinberg model.
- Indicate the conditions under which allelic frequencies (p and q) remain constant from one generation to the next.
- Calculate, showing all work, the frequencies of the alleles and the frequencies of the genotypes in a population of 100,000 rabbits, of which 25,000 are white and 75,000 are agouti. (In rabbits the white color is due to a recessive allele, w, and the agouti is due to a dominant all, W.)
- If the homozygous dominant condition were to become lethal, what would happen to the allelic and genotypic frequencies in the rabbit population after two generations?
33. Evolution is one of the major unifying themes of modern biology.
- Explain the mechanisms that lead to evolutionary change.
- Describe how scientists use each of the following as evidence for evolution.
- Bacterial resistance to antibodies.
- Comparative biochemistry.
- The fossil record.
34. Genetic variation is the raw material for evolution.
- Explain three cellular and/or molecular mechanisms that introduce variation into the gene pool of a plant or animal population.
- Explain the evolutionary mechanisms that can change the composition of the gene pool.
35. In a laboratory population of diploid, sexually reproducing organisms a certain trait is studied. This trait is determined by a single autosomal gene and is expressed as two phenotypes. A new population was created by crossing 51 pure breeding (homozygous) dominant individuals with 49 pure breeding (homozygous) individuals. After four generations, the following results were obtained.
- Identify an organism that might have been used to perform this experiment, and explain why this organism is a good choice for conducting this experiment.
- On the basis of the data, propose a hypothesis that explains the change in phenotypic frequency between generation 1 and generation 3.
- Is there evidence indicating whether or not this population is in Hardy-Weinberg equilibrium? Explain.
Number of Individuals
Unit 8 (Chemical Evolution, Prokaryotes, Eukaryote Evolution, Protista)
36. Scientists recently have proposed a reorganization of the phylogenetic system of classification to include the domain, a new taxonomic category higher (more inclusive) than the Kingdom category, as shown in the following diagram.
Domain Bacteria Domain Archaea Domain Eukarya
(Eubacteria) (Archaebacteria) (Eukaryotes)
- describe how this classification scheme presents different conclusions about the relationships among living organisms than those presented by the previous five-kingdom system of classification
- describe three kinds of evidence that were used to develop the taxonomic scheme above, and explain how this evidence was used. The evidence may be structural, physiological, molecular, and/or genetic.
- Describefour of the characteristics of the universal ancestor.
Unit 9 (Introduction to Plants, Fungi, Invertebrates)
37. In the life cycles of a fern and a flowering plant, compare and contrast each of the following:
- The gametophyte generation.
- Sperm transport and fertilization.
- Embryo protection.
38. Describe the differences between the terms in each of the following pairs.
- Coelomate versus acoelomate body plan.
- Protostome versus deuterostome development.
- Radial versus bilateral symmetry.
- Explain how each of these pairs of features was important in constructing the phylogenetic tree shown below. Use specific examples from the tree in your discussion.
Unit 10 (Vertebrates, Basic Animal Structure and Function)
39. Select two of the following three pairs and discuss the evolutionary relationships between the two members of each pair you have chosen. In your discussion include structural adaptations and the functional significance.
Pair A: green algae—vascular plants
Pair B: prokaryotes—eukaryotes
Pair C: amphibians—reptiles
Unit 11 (Animal Nutrition, Circulation, Respiration, Immune System)
40. Describe the structure of a mammalian respiratory system. Include in your discussion the mechanisms of inspiration and expiration.
41. Describe the processes of fat and protein digestion and product absorption as they occur in the human stomach and small intestine. Include a discussion of the enzymatic reactions involved.
42. Describe the following mechanisms of response to foreign materials in the human body.
- The antigen-antibody response to a skin graft from another person.
- The reactions of the body leading to inflammation of a wound infected by bacteria.
43. Discuss the processes of exchange of O2 and CO2 that occur at the alveoli and muscle cells of mammals. Include in your answer a description of the transport of these gases in the blood.
44. Many physioligical changes occur during exercise.
- Design a controlled experiment to test the hypothesis that an exercise session causes short-term increases in heart rat and breathing rate in humans.
- Explain how at least three organ systems are affected by this increased physical activity and discuss interactions among these systems.
45. The graph below shows the response of the human immune system to exposure to an antigen. Use this graph to answer part a and part b of this question.
- Describe the events that occur during period I as the immune system responds to the initial exposure to the antigen.
- Describe the events that occur during period II following a second exposure to the same antigen.
- Explain how infection by the AIDS virus (HIV) affects the function of both T and B lymphocytes.
Unit 12 (Homeostasis, Reproduction, Development)
47. Discuss the processes of cleavage, gastrulation, and neurulation in the frog embryo; tell what each process accomplishes. Describe an experiment that illustrates the importance of induction in development.
48. The evolutionary success of organisms depends on reproduction. Some groups of organisms reproduce asexually, some reproduce sexually, while others reproduce both sexually and asexually.
- Using THREE difference organisms, give an example of one organism that reproduces sexually, one that reproduces asexually, and one that reproduces BOTH sexually and asexually. For each organism given as an example, describe two reproductive adaptations. These adaptations may be behavioral, structural, and/or functional.
- What environmental conditions would favor sexual reproduction? Explain. What environmental conditions would favor asexual reproduction? Explain.
Unit 13 (Endocrine System, Nervous System, Sensory and Motor Mechanisms)
49. Discuss the sources and actions of each of the following pairs of hormones in humans and describe the feedback mechanisms that control their release.
- Parathyroid hormone—calcitonin
- Thyrotropin (TSH)—thyroxine (T4)
50. Beginning at the presynaptic membrane of the neuromuscular junction, describe the physical and biochemical events involved in the contraction of a skeletal muscle fiber. Include the structure of the fiber in your discussion.
52. Describe the negative and positive feedback loops, and discuss how feedback mechanisms regulate each of the following.
- The menstrual cycle in nonpregnant human female.
- Blood glucose levels in humans.
53. Discuss how cellular structures, including the plasma membrane, specialized endoplasmic reticulum, cytoskeletal elements, and mitochondria, function together in the contraction of skeletal muscle cells.
54. Structure and function are related in the various organ systems of animals. Select two of the following four organ systems in vertebrates:
For each of the two systems you choose, discuss the structure and function of two adaptations that aid in the transport or exchange of molecules (or ions). Be sure to relate structure to function in each example.
Unit 14 (Plant Structure and Function)
55. Relate the structure of an angiosperm leaf to each of the following:
- Adaptations for photosynthesis and food storage.
- Adaptations for food translocation and water transport.
- Specialized adaptations to a desert environment.
56. Define the following plant responses and explain the mechanism of control for each. Cite experimental evidence as part of your discussion.
57. Describe the structure of a bean seed and discuss its germination to the seedling stage. Include in your essay hormonal controls, structural changes, and tissue differentiation.
58. Describe the effects of plant hormones on plant growth and development. Design an experiment to demonstrate the effect of one of these plant hormones on plant growth and development.
59. Trace the pathway in a flowering plant as the water moves from the soil through the tissues of the root, stem, and leaves to the atmosphere. Explain the mechanisms involved in conducting water through these tissues.
60. Discuss the adaptations that have enabled flowering plants to overcome the following problems associated with life on land.
- The absence of an aquatic environment for reproduction.
- The absence of an aquatic environment to support the plant body.
- Dehydration of the plant.
61. A group of students designed an experiment to measure transpiration rates in a particular species of herbaceous plant. Plants were divided into four groups and were exposed to the following conditions.
- Construct and label a graph using the data for Group I. Using the same set of axes, draw and label three additional lines representing the results that you would predict for Groups II, III, and IV.
- Explain how biological and physical processes are responsible for the difference between each of your predictions and the data for Group I.
- Explain how the concept of water potential is used to account for the movement of water from the plant stem to the atmosphere during transpiration.
|Group I-||Room conditions (light, low humidity, 20° C, and little air movement.)|
|Group II-||Room conditions with increased humidity.|
|Group III-||Room conditions with increased air movement (fan)|
|Group IV-||Room conditions with additional light|
The cumulative water loss due to transpiration of water from each plant was measured at 10-minute intervals for 30 minutes. Water loss was expressed as milliliters of water per square centimeter of leaf surface area. The data for all plants in Group I (room conditions) were averaged. The average cumulative water loss by the plants in Group I is presented in the table below.
Average Cumulative Water Loss by the Plants in Group I
Average Cumulative Water Loss (milliliter H2O centimeter2)
3.5 x 10-4
7.7 x 10-4
10.6 x 10-4
62. Numerous environmental variables influence plant growth. Three students each planted a seedling of the same genetic variety in the same type of container with equal amounts of soil from the same source. Their goal was to maximize their seedling’s growth by manipulating environmental conditions. Their data are shown below.
- Identify three different environmental variables that could account for differences in the mass of seedlings at day 30. Then choose one of these variables and design an experiment to test the hypothesis that your variable affects growth of these seedlings.
- Discuss the results you would expect if your hypothesis is correct. Then provide a physiological explanation for the effect of your variable on plant growth.
|Plant Seedling Mass (grams)|
|Day 1||Day 30|
Unit 15 (Ecology)
63. Define and explain the role of each of the following in social behavior.
- Dominance hierarchies.
- Courtship behavior.
64. Describe the trophic levels in a typical ecosystem. Discuss the flow of energy through the ecosystem, the relationship between the different trophic levels, and the factors that limit the number of trophic levels.
65. Describe and give an example of each of the following. Include in your discussion the selection advantage of each.
- Stereotyped behavior (instinct).
66. Describe the process of ecological succession from a pioneer community to a climax community. Include in your answer a discussion of species diversity and interactions, accumulation of biomass, and energy flow.
67. Describe releasers, imprinting, and communications, as each of these terms relates to animal behavior. You may include in your answer a discussion of the classical studies of Niko Tinbergen, Konrad Lorenz, and Karl von Frisch.
68. Describe the biogeochemical cycles of carbon and nitrogen. Trace these elements from the point of their release from a decaying animal to their incorporation into a living animal.
69. Using an example for each, discuss the following ecological concepts.
- Energy flow between trophic levels.
- Limiting factors.
- Carrying capacity.
70. Living organisms play an important role in the recycling of many elements within an ecosystem. Discuss how various types of organisms and their biochemical reactions contribute to the recycling of either carbon or nitrogen in an ecosystem. Include in your answer one way in which human activity has an impact in the nutrient cycle you have chosen.
71. Survival depends on the ability of an organism to respond to changes in its environment. Some plants flower in response to changes in day length. Some mammals may run or fight when frightened. For both of these examples, describe the physiological mechanisms involved in the response.
72. Interdependence in nature is illustrated by the transfer of energy through trophic levels. The diagram below depicts the transfer of energy in a food web of an Arctic lake located in Alaska (J )
- Choosing organisms from four different trophic levels of this food web as examples, explain how energy is obtained at each trophic level.
- Describe the efficiency of energy transfer between trophic levels and discuss how the amount of energy available at each trophic level affects the structure of the ecosystem.
- If the cells in the dead terrestrial plant material that washed into the lake contained a commercially produced toxin, what would be the likely effects of this toxin on this food web? Explain.
For the data above, provide information on each of the following.
- Summarize the pattern.
- Identify THREE physiological or environmental variables that could cause the slugs to vary their distance from each other.
- Explain how each variable could bring about the observed pattern of distribution.
Choose ONE of the variables that you identified and design a controlled experiment to test your hypothetical explanation. Describe results that would support or refute your hypothesis.
74. Describe how the following adaptations have increased the evolutionary success of the organisms that possess them. Include in your discussion the structure and function related to each adaptation.
- C4 metabolism
- Amniotic egg
- Four-chambered heart
75. Describe the anatomical and functional similarities and difference within each of the following pairs of structures.
- Small intestine—colon
- Skeletal muscle—cardiac muscle
- Anterior pituitary—posterior pituitary
76. Discuss how each of the following has contributed to the evolutionary success of the organisms in which they are found.
- mammalian placenta
77. Angiosperms (flowering plants) and vertebrates obtain nutrients from their environment in different ways.
- Discuss the type of nutrition and the nutritional requirements of angiosperms and vertebrates.
- Describe 2 structural adaptations in angiosperms for obtaining nutrients from the environment. Relate structure to function.
- Interdependence in nature is evident in symbiosis. Explain tow symbiotic relationships that aid in nutrient uptake, using examples from angiosperms and/or vertebrates. (Both examples may be angiosperms, both may be vertebrates, or one may be from each group.
78. The problem of survival of animals on land are very different from those of survival of animals in an aquatic environment. Describe four problems associated with animal survival in terrestrial environments but not in aquatic environments. For each problem, explain an evolutionary solution.
79. The survival of organisms depends on regulatory mechanisms at various levels. Choose THREE from the following examples. Explain how each is regulated.
- The expression of a gene.
- The activity of an enzyme.
- The cell cycle.
- The internal water balance of a plant.
- The density of a population.
80. Photosynthesis and cellular respiration recycle oxygen in ecosystems. Respond to TWO (and only two) of the following:
- Explain how the metabolic processes of cellular respiration and photosynthesis recycle oxygen.
- Discuss the structural adaptations that function in oxygen exchange between each of the following organisms and its environment: a plant; an insect; a fish.
- Trace a molecule of O2 from the environment to a muscle cell in a vertebrate of your choice.
81. Biological recognition is important in many processes at the molecular, cellular, tissue, and organismal levels. Select three of the following, and for each of the three that you have chose, explain how the process of recognition occurs and give an example of each.
- Organisms recognize others as members of their own species.
- Neurotransmitters are recognized in the synapse.
- Antigens trigger antibody response.
- Nucleic acids are complementary.
- Target cells respond to specific hormones.
82. Communication occurs among the cells in a multicellular organism. Choose THREE of the following examples of cell-to-cell communication, and for each example, describe the communication that occurs and the types of responses that result from this communication.
- communication between two plant cells
- communication between two immune-system cells
- communication either between a neuron and another neuron, or between a neuron and a muscle cell
- communication between a specific endocrine-gland cell and its target cell
A fundamental task of proteins is to act as enzymes—catalysts that increase the rate of virtually all the chemical reactions within cells. Although RNAs are capable of catalyzing some reactions, most biological reactions are catalyzed by proteins. In the absence of enzymatic catalysis, most biochemical reactions are so slow that they would not occur under the mild conditions of temperature and pressure that are compatible with life. Enzymes accelerate the rates of such reactions by well over a million-fold, so reactions that would take years in the absence of catalysis can occur in fractions of seconds if catalyzed by the appropriate enzyme. Cells contain thousands of different enzymes, and their activities determine which of the many possible chemical reactions actually take place within the cell.
The Catalytic Activity of Enzymes
Like all other catalysts, enzymes are characterized by two fundamental properties. First, they increase the rate of chemical reactions without themselves being consumed or permanently altered by the reaction. Second, they increase reaction rates without altering the chemical equilibrium between reactants and products.
These principles of enzymatic catalysis are illustrated in the following example, in which a molecule acted upon by an enzyme (referred to as a substrate [S]) is converted to a product (P) as the result of the reaction. In the absence of the enzyme, the reaction can be written as follows:
The chemical equilibrium between S and P is determined by the laws of thermodynamics (as discussed further in the next section of this chapter) and is represented by the ratio of the forward and reverse reaction rates (S→P and P→S, respectively). In the presence of the appropriate enzyme, the conversion of S to P is accelerated, but the equilibrium between S and P is unaltered. Therefore, the enzyme must accelerate both the forward and reverse reactions equally. The reaction can be written as follows:
Note that the enzyme (E) is not altered by the reaction, so the chemical equilibrium remains unchanged, determined solely by the thermodynamic properties of S and P.
The effect of the enzyme on such a reaction is best illustrated by the energy changes that must occur during the conversion of S to P (Figure 2.22). The equilibrium of the reaction is determined by the final energy states of S and P, which are unaffected by enzymatic catalysis. In order for the reaction to proceed, however, the substrate must first be converted to a higher energy state, called the transition state. The energy required to reach the transition state (the activation energy) constitutes a barrier to the progress of the reaction, limiting the rate of the reaction. Enzymes (and other catalysts) act by reducing the activation energy, thereby increasing the rate of reaction. The increased rate is the same in both the forward and reverse directions, since both must pass through the same transition state.
Energy diagrams for catalyzed and uncatalyzed reactions. The reaction illustrated is the simple conversion of a substrate S to a product P. Because the final energy state of P is lower than that of S, the reaction proceeds from left to right. For the (more...)
The catalytic activity of enzymes involves the binding of their substrates to form an enzyme-substrate complex (ES). The substrate binds to a specific region of the enzyme, called the active site. While bound to the active site, the substrate is converted into the product of the reaction, which is then released from the enzyme. The enzyme-catalyzed reaction can thus be written as follows:
Note that E appears unaltered on both sides of the equation, so the equilibrium is unaffected. However, the enzyme provides a surface upon which the reactions converting S to P can occur more readily. This is a result of interactions between the enzyme and substrate that lower the energy of activation and favor formation of the transition state.
Mechanisms of Enzymatic Catalysis
The binding of a substrate to the active site of an enzyme is a very specific interaction. Active sites are clefts or grooves on the surface of an enzyme, usually composed of amino acids from different parts of the polypeptide chain that are brought together in the tertiary structure of the folded protein. Substrates initially bind to the active site by noncovalent interactions, including hydrogen bonds, ionic bonds, and hydrophobic interactions. Once a substrate is bound to the active site of an enzyme, multiple mechanisms can accelerate its conversion to the product of the reaction.
Although the simple example discussed in the previous section involved only a single substrate molecule, most biochemical reactions involve interactions between two or more different substrates. For example, the formation of a peptide bond involves the joining of two amino acids. For such reactions, the binding of two or more substrates to the active site in the proper position and orientation accelerates the reaction (Figure 2.23). The enzyme provides a template upon which the reactants are brought together and properly oriented to favor the formation of the transition state in which they interact.
Enzymatic catalysis of a reaction between two substrates. The enzyme provides a template upon which the two substrates are brought together in the proper position and orientation to react with each other.
Enzymes accelerate reactions also by altering the conformation of their substrates to approach that of the transition state. The simplest model of enzyme-substrate interaction is the lock-and-key model, in which the substrate fits precisely into the active site (Figure 2.24). In many cases, however, the configurations of both the enzyme and substrate are modified by substrate binding—a process called induced fit. In such cases the conformation of the substrate is altered so that it more closely resembles that of the transition state. The stress produced by such distortion of the substrate can further facilitate its conversion to the transition state by weakening critical bonds. Moreover, the transition state is stabilized by its tight binding to the enzyme, thereby lowering the required energy of activation.
Models of enzyme-substrate interaction. (A) In the lock-and-key model, the substrate fits precisely into the active site of the enzyme. (B) In the induced-fit model, substrate binding distorts the conformations of both substrate and enzyme. This distortion (more...)
In addition to bringing multiple substrates together and distorting the conformation of substrates to approach the transition state, many enzymes participate directly in the catalytic process. In such cases, specific amino acid side chains in the active site may react with the substrate and form bonds with reaction intermediates. The acidic and basic amino acids are often involved in these catalytic mechanisms, as illustrated in the following discussion of chymotrypsin as an example of enzymatic catalysis.
Chymotrypsin is a member of a family of enzymes (serine proteases) that digest proteins by catalyzing the hydrolysis of peptide bonds. The reaction can be written as follows:
The different members of the serine protease family (including chymotrypsin, trypsin, elastase, and thrombin) have distinct substrate specificities; they preferentially cleave peptide bonds adjacent to different amino acids. For example, whereas chymotrypsin digests bonds adjacent to hydrophobic amino acids, such as tryptophan and phenylalanine, trypsin digests bonds next to basic amino acids, such as lysine and arginine. All the serine proteases, however, are similar in structure and use the same mechanism of catalysis. The active sites of these enzymes contain three critical amino acids—serine, histidine, and aspartate—that drive hydrolysis of the peptide bond. Indeed, these enzymes are called serine proteases because of the central role of the serine residue.
Substrates bind to the serine proteases by insertion of the amino acid adjacent to the cleavage site into a pocket at the active site of the enzyme (Figure 2.25). The nature of this pocket determines the substrate specificity of the different members of the serine protease family. For example, the binding pocket of chymotrypsin contains hydrophobic amino acids that interact with the hydrophobic side chains of its preferred substrates. In contrast, the binding pocket of trypsin contains a negatively charged acidic amino acid (aspartate), which is able to form an ionic bond with the lysine or arginine residues of its substrates.
Substrate binding by serine proteases. The amino acid adjacent to the peptide bond to be cleaved is inserted into a pocket at the active site of the enzyme. In chymotrypsin, the pocket binds hydrophobic amino acids; the binding pocket of trypsin contains (more...)
Substrate binding positions the peptide bond to be cleaved adjacent to the active site serine (Figure 2.26). The proton of this serine is then transferred to the active site histidine. The conformation of the active site favors this proton transfer because the histidine interacts with the negatively charged aspartate residue. The serine reacts with the substrate, forming a tetrahedral transition state. The peptide bond is then cleaved, and the C-terminal portion of the substrate is released from the enzyme. However, the N-terminal peptide remains bound to serine. This situation is resolved when a water molecule (the second substrate) enters the active site and reverses the preceding reactions. The proton of the water molecule is transferred to histidine, and its hydroxyl group is transferred to the peptide, forming a second tetrahedral transition state. The proton is then transferred from histidine back to serine, and the peptide is released from the enzyme, completing the reaction.
Catalytic mechanism of chymotrypsin. Three amino acids at the active site (Ser-195, His-57, and Asp-102) play critical roles in catalysis.
This example illustrates several features of enzymatic catalysis; the specificity of enzyme-substrate interactions, the positioning of different substrate molecules in the active site, and the involvement of active-site residues in the formation and stabilization of the transition state. Although the thousands of enzymes in cells catalyze many different types of chemical reactions, the same basic principles apply to their operation.
In addition to binding their substrates, the active sites of many enzymes bind other small molecules that participate in catalysis. Prosthetic groups are small molecules bound to proteins in which they play critical functional roles. For example, the oxygen carried by myoglobin and hemoglobin is bound to heme, a prosthetic group of these proteins. In many cases metal ions (such as zinc or iron) are bound to enzymes and play central roles in the catalytic process. In addition, various low-molecular-weight organic molecules participate in specific types of enzymatic reactions. These molecules are called coenzymes because they work together with enzymes to enhance reaction rates. In contrast to substrates, coenzymes are not irreversibly altered by the reactions in which they are involved. Rather, they are recycled and can participate in multiple enzymatic reactions.
Coenzymes serve as carriers of several types of chemical groups. A prominent example of a coenzyme is nicotinamide adenine dinucleotide (NAD+), which functions as a carrier of electrons in oxidation-reduction reactions (Figure 2.27). NAD+ can accept a hydrogen ion (H+) and two electrons (e-) from one substrate, forming NADH. NADH can then donate these electrons to a second substrate, re-forming NAD+. Thus, NAD+ transfers electrons from the first substrate (which becomes oxidized) to the second (which becomes reduced).
Role of NAD+ in oxidation-reduction reactions. (A) Nicotinamide adenine dinucleotide (NAD+) acts as a carrier of electrons in oxidation-reduction reactions by accepting electrons (e-) to form NADH. (B) For example, NAD+ can accept electrons from one substrate (more...)
Several other coenzymes also act as electron carriers, and still others are involved in the transfer of a variety of additional chemical groups (e.g., carboxyl groups and acyl groups; Table 2.1). The same coenzymes function together with a variety of different enzymes to catalyze the transfer of specific chemical groups between a wide range of substrates. Many coenzymes are closely related to vitamins, which contribute part or all of the structure of the coenzyme. Vitamins are not required by bacteria such as E. coli but are necessary components of the diets of human and other higher animals, which have lost the ability to synthesize these compounds.
Regulation of Enzyme Activity
An important feature of most enzymes is that their activities are not constant but instead can be modulated. That is, the activities of enzymes can be regulated so that they function appropriately to meet the varied physiological needs that may arise during the life of the cell.
One common type of enzyme regulation is feedback inhibition, in which the product of a metabolic pathway inhibits the activity of an enzyme involved in its synthesis. For example, the amino acid isoleucine is synthesized by a series of reactions starting from the amino acid threonine (Figure 2.28). The first step in the pathway is catalyzed by the enzyme threonine deaminase, which is inhibited by isoleucine, the end product of the pathway. Thus, an adequate amount of isoleucine in the cell inhibits threonine deaminase, blocking further synthesis of isoleucine. If the concentration of isoleucine decreases, feedback inhibition is relieved, threonine deaminase is no longer inhibited, and additional isoleucine is synthesized. By so regulating the activity of threonine deaminase, the cell synthesizes the necessary amount of isoleucine but avoids wasting energy on the synthesis of more isoleucine than is needed.
Feedback inhibition. The first step in the conversion of threonine to iso-leucine is catalyzed by the enzyme threonine deaminase. The activity of this enzyme is inhibited by isoleucine, the end product of the pathway.
Feedback inhibition is one example of allosteric regulation, in which enzyme activity is controlled by the binding of small molecules to regulatory sites on the enzyme (Figure 2.29). The term “allosteric regulation” derives from the fact that the regulatory molecules bind not to the catalytic site, but to a distinct site on the protein (allo= “other” and steric= “site”). Binding of the regulatory molecule changes the conformation of the protein, which in turn alters the shape of the active site and the catalytic activity of the enzyme. In the case of threonine deaminase, binding of the regulatory molecule (isoleucine) inhibits enzymatic activity. In other cases regulatory molecules serve as activators, stimulating rather than inhibiting their target enzymes.
Allosteric regulation. In this example, enzyme activity is inhibited by the binding of a regulatory molecule to an allosteric site. In the absence of inhibitor, the substrate binds to the active site of the enzyme and the reaction proceeds. The binding (more...)
The activities of enzymes can also be regulated by their interactions with other proteins and by covalent modifications, such as the addition of phosphate groups to serine, threonine, or tyrosine residues. Phosphorylation is a particularly common mechanism for regulating enzyme activity; the addition of phosphate groups either stimulates or inhibits the activities of many different enzymes (Figure 2.30). For example, muscle cells respond to epinephrine (adrenaline) by breaking down glycogen into glucose, thereby providing a source of energy for increased muscular activity. The breakdown of glycogen is catalyzed by the enzyme glycogen phosphorylase, which is activated by phosphorylation in response to the binding of epinephrine to a receptor on the surface of the muscle cell. Protein phosphorylation plays a central role in controlling not only metabolic reactions but also many other cellular functions, including cell growth and differentiation.
Protein phosphorylation. Some enzymes are regulated by the addition of phosphate groups to the side-chain OH groups of serine (as shown here), threonine, or tyrosine residues. For example, the enzyme glycogen phosphorylase, which catalyzes the conversion (more...)