Catalyzing Student Learning: Using Analogies To Teach Enzyme

Article Cite This: J. Chem. Educ. 2019, 96, 1401−1406

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Catalyzing Student Learning: Using Analogies To Teach Enzyme Kinetics Jon-Marc G. Rodriguez and Marcy H. Towns* Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States

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S Supporting Information *

ABSTRACT: Analogies are useful tools instructors can use to help make challenging concepts less abstract by drawing connections to familiar contexts. In this paper we provide an overview of the various analogies published in the education literature that are situated in the context of enzyme kinetics, including narrative-based analogies (analogies intended to be presented by an instructor in a lecture setting) and activity-based analogies (analogies that serve as the basis for interactive tasks intended to be completed by students in a laboratory/small group setting). After discussing the published analogies, we present an analogy we developed that incorporates previous research regarding the effective use and presentation of analogies in biochemistry. Our analogy focuses on supporting students in distinguishing between the different types of enzyme inhibitors, which has been previously determined to be challenging for students. KEYWORDS: Upper-Division Undergraduate, Biochemistry, Enzymes, Kinetics, Interdisciplinary/Multidisciplinary, Analogies/Transfer

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s discussed by Ausubel,1 in order to move beyond rote memorization and promote meaningful learning, new knowledge must build on and connect to prior knowledge. One way to draw connections between challenging new concepts and students’ previous experiences is through the use of analogies. In the context of instruction, analogies serve the role of helping students understand an idea (i.e., target domain) by drawing a comparison to something more familiar (i.e., analog domain).2 Common examples of analogies used in biochemistry and biology include describing enzyme−substrate complementarity as a “lock and key” or describing the mitochondria as the “powerhouse” of the cell. Research by Orgill and colleagues2,3 indicates biochemistry textbooks and biochemistry faculty frequently use analogies to explain concepts. Furthermore, students tended to have favorable views of the use of analogies in biochemistry courses, with students stating that analogies helped them understand challenging topics, remember ideas, and improve their motivation to learn the content.4,5 In this paper we provide an overview of analogies published in the education literature, focusing on analogies used to describe enzyme kinetics. The interest in enzyme kinetics © 2019 American Chemical Society and Division of Chemical Education, Inc.

analogies stemmed from work by the authors that investigated how students reason about enzyme kinetics, in which it was noted there was a lack of research on the teaching and learning of enzyme kinetics,6,7 but there was a rich body of resources for practitioners, including a variety of analogies that can be used to explain enzyme kinetics.8−19 Most of these analogies and analogy-based activities were published in this Journal, due to the variety of manuscript types available for publication (e.g., articles, commentaries, activities, etc.). After presenting an overview of the different analogies and the aspects of enzyme kinetics addressed in each analogy, an analogy for enzyme kinetics is presented by the authors that (1) incorporates evidence-based practices related to analogies (informed by the work of Orgill and colleagues)2−5 and (2) specifically addresses an aspect of enzyme kinetics determined to be challenging for students based on our recent research related to enzyme inhibition.6 Received: January 3, 2019 Revised: April 9, 2019 Published: May 24, 2019 1401

DOI: 10.1021/acs.jchemed.9b00004 J. Chem. Educ. 2019, 96, 1401−1406

Bean

Student

Student

Junker (2010),12 Lechner (2011),13 Silverstein (2011)17 Hinckley (2012)10

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a

Penny

Marble

Honey Contraband

Removing the bean from the paper bag Placing the penny in the falcon tube

Moving the marble from one container to another Unscrewing the nut from the bolt

a a

× ×

× ×

×

×

×

×

× ×

×

×

×

×

×

Activity-Based Analogy × ×

×

×

Vmax (Saturation)

Narrative-Based Analogy

Substrate Concn

× ×

Competitive Inhibition

×

×

×

×

×

Noncompetitive Inhibition

×

×

×

×

Enzyme Concn

Ochs (2000)15 did not clearly specify the catalytic event, primarily using analogies to describe uncompetitive inhibition in general terms.

House et al. (2016)11

Student holding a falcon tube

Nut screwed onto a bolt

Student

Runge et al. (2006)18

Ochs (2000)15 Ochs (2000)15

Cutting off the goose’s head

Goose

Child holding a pin Butcher with knife and chopping block Bear Suspect

Unlocking the lock Crushing the pingpong ball Popping the balloon

Catalytic Event

Key Ping-pong ball Balloon

Abel and Halenz (1992)9 Silverstein (1995)16

Substrate

Lock Person

Enzyme

Asimov (1959)8 Helser (1991)19

Publication

Table 1. Features of Enzyme Kinetics Addressed in Each Analogy, Ordered in Terms of Frequency

×

×

×

Irreversible Inhibition

×

×

×

Specificity

×

×

×

Reaction Scheme

×

×

×

Temp

×

× ×

Uncompetitive Inhibition

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DOI: 10.1021/acs.jchemed.9b00004 J. Chem. Educ. 2019, 96, 1401−1406

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ENZYME KINETICS ANALOGIES The overview of analogies in the literature can be divided into two main categories: narrative-based analogies and activity-based analogies. This distinction between the types of analogies is not meant to imply that the activity-based analogies do not involve a clear story, but rather to highlight the interactive nature of the activity-based analogies (in contrast, the narrative-based analogies are intended to be described by an instructor in a lecture setting). Moreover, our discussion is limited to published enzyme kinetics analogies discussed in peerreviewed academic journals.

The butcher steadies the goose on a specially designed chopping block (binding site) that orients the neck (labile bond) optimally for chopping (bond cleavage). The enzyme/butcher uses a specially sharpened knife (a critical nucleophile or coenzyme) for cutting. The active site consists of the butcher’s arm and knife, poised over the fowl’s neck. The binding site on the chopping block holds the animal (substrate). This particularly descriptive analogy then provided further detail, using this context to draw connections to kcat, activation energy, cooperativity, allosteric effects, and a qualitative description of Km as binding affinity, among other concepts.

Narrative-Based Analogies

Activity-Based Analogies

There was much more variety among the narrative-based analogies in comparison to the activity-based analogies. However, the general sentiment of the narrative-based analogies was the same: a more familiar context was used to describe enzyme kinetics, with each of the analogies in this category varying in terms of how developed the analogy was and how many features of enzyme kinetics were discussed. Some of the analogies were simple and focused on a single feature of enzyme inhibition, such as the analogy described by Asimov,8 which discussed competitive inhibition in the context of the “lock-and-key” model of enzyme−substrate interactions (a competitive inhibitor is analogous to a key that only fits in and occupies the lock, but does not have the correct grooves and fine-grained details to unlock the lock). Similarly, Ochs15 used two simple analogies to describe enzyme inhibition, exclusively focusing on the fact that uncompetitive inhibitors can only bind the enzyme−substrate complex: a bear (“the enzyme”) grabs honey (“the substrate”) from a bee hive (“the uncompetitive inhibitor”) and gets its paw stuck; a suspect (“the enzyme”) attempts to purchase illegal contraband (“the substrate”) and is arrested by a law enforcement agent (“the uncompetitive inhibitor”). Both of these analogies used by Ochs15 illustrated that the inhibition (the “honey trap” or “sting operation”) could not occur without both the enzyme and the substrate (i.e., the presence of the enzyme−substrate complex is necessary). Other analogies were surprisingly developed and complex in terms of the features of enzyme kinetics addressed. Abel and Halenz9 presented a seemingly innocuous analogy, in which enzyme catalysis was represented by a child (“the enzyme”) and a balloon (“the substrate”), where the catalytic event involved the child popping a balloon. Building on this idea, it was discussed that increasing the number of balloons influences rate, up to a limit (i.e., reaching Vmax), and the role of optimal temperature for enzyme functionality was addressedthe child would not be able to pop balloons as well if the temperature was too high or too low. The analogy was also used to describe reversible enzyme inhibition (competitive and noncompetitive); however, this analogy took a bit of a dark turn when it discussed irreversible enzyme inhibition, stating this was analogous to the child dying. On a similar note, Silverstein16 provided a particularly graphic description of enzyme−substrate interactions in the context of enzyme kinetics, best communicated by the article title, “Breaking Bonds versus Chopping Heads: The Enzyme as Butcher”. In his analogy, Silverstein16 described a butcher with a knife and a chopping block (“the enzyme”) that cuts the head off of a goose (“the substrate”), reflecting the catalytic event that produces a product (i.e., the severed fowl):

Activity-based analogies were largely the same, typically involving students working in groups using a simple model to describe enzyme kinetics and enzyme inhibition.10−13,17,18 In most cases catalysis was represented by having the students transfer an object to a container10,11,18 or, alternatively, unscrew a nut and bolt.12,13,17 In these analogies, the student represents the enzyme; their hands represent the active site, and the transferred object (e.g., marble, bean, penny) is the substrate. These activities were then used as a context to collect “kinetic” data, in which the students tabulated the number of “product” molecules that were formed for a given time interval, from which velocity (rate) could be calculated and subsequently graphed. Then, on the basis of the data obtained in these activities, students are prompted to draw conclusions regarding the kinetic parameters, Km and Vmax, and discuss the influence enzyme inhibitors have on these parameters. Each of the different activities had features that were unique to the specific activity; for example, Rung et al.’s activity,18 published in CBELife Sciences Education, approached enzyme kinetics from a biological perspective, focusing on how enzyme kinetics serves as the basis for studying membrane transporters such as permeases. In addition, in contrast to the other activities, Runge et al.18 emphasized the importance of understanding and calculating the turnover number associated with a particular enzyme. It is also interesting to note that the activity involving unscrewing a nut from a bolt was originally published by Junker,12 but others added to this experiment to expand the analogy or clarify specific points.13,17 For example, Lechner13 added to the activity by discussing how to model product inhibition, and Silverstein17 made some suggestions to build in considerations regarding how enzyme concentration influences rate. Comparison of the Analogies

Looking across the analogies from both categories, various enzyme kinetics ideas were discussed. In Table 1, a list of each of the analogies is provided, along with the features of enzyme kinetics addressed in each analogy (ordered on the basis of frequency from left to right). In the process of constructing Table 1, concepts covered in the analogies were only included if they were addressed by at least two analogies. For example, although House et al.11 described the role of pH on the function of the enzyme in their analogy (in addition to other ideas), it was not included in the table, since it was specific to their analogy. Generally, the most common concepts addressed in the analogies were competitive inhibition and the concentration-dependence of rate (along with implications for Vmax), whereas the analogies less frequently discussed uncompetitive inhibition and the role of temperature on the 1403

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Figure 1. Summary of our enzyme kinetics analogy, which was designed to help students distinguish between the different types of enzyme inhibition. In this analogy each runner plays by their own “set of rules” to cross the finish line and win the prize, where “winning the prize” represents the inhibitor binding the enzyme.

additional analogy, designed and informed by previous research. The potential benefits of analogies have been noted, and here we describe the features that characterize an effective analogy in biochemistry instruction, as noted by Orgill and colleagues,3−5 summarized in Box 1. The order of the

functionality of the enzyme. It can also be noted that the activity-based analogies were all published more recently, in contrast to the narrative-based analogies. It is also worth noting that Table 1 draws a distinction between what was discussed as part of the analogies versus what was explicitly addressed in activities. For example, the activity-based analogies involved analyzing and interpreting the data collected using the analogy/model, in which students calculated values such as Km; however, calculating Km from data does not have a clear analog−target connection. In this context, Km is treated mathematically the same as the Km associated with kinetic data obtained through other means; this is distinct from an analogy that uses an analog context to provide a qualitative understanding of Km by describing the interactions that occur at the “chopping block”, to use Silverstein’s16 fowl analogy. Thus, Table 1 only encompasses aspects of enzyme kinetics discussed in analogies containing clear analog−target connections. In addition, although it was not mentioned previously or shown in Table 1, there was an analogy described by Murkin14 that does not fit with the previously discussed narrative-based and activity-based categories. All of the previous analogies qualitatively described a concept, but Murkin’s14 analogy is more of an algorithmic tool that draws a connection between Ohm’s law and the relationship between rate constants in multistep reactions.

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Box 1. Features of the Effective Use and Presentation of Analogies in Biochemistry Instruction (Orgill and Colleagues3−5) 1. Intentional: Analogies should be carefully developed in advance for challenging topics. 2. Familiar: Analogies should involve a context that is relatable and accessible to a large and broad audience. 3. Simple: Analogies should be short and easy to remember. 4. Clear: Analogies should be presented in a way that draws explicit connections between the analog context and the target concept, using visuals to support these connections. 5. Bounded: The limits of the analogy (i.e., model) should be discussed to prevent its inappropriate application or extension. ideas discussed in Box 1 is relevant, because development of an analogy that incorporates these ideas requires intentionality (the first feature listed). In a study that focused on faculty perception and use of analogies, Orgill, Bussey, and Bodner2 discussed how instructors may be unaware of how frequently they used analogies and often used analogies as a spur-of-the-

ONE MORE ENZYME KINETICS ANALOGY

Developing an Analogy Informed by Research

As discussed previously, the intent is to not only provide an overview of enzyme kinetics analogies, but also to present an 1404

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Figure 2. Connection between the analogy and the target concepts. Adapted from ref 6 with permission from The Royal Society of Chemistry.

moment tool when students appeared confused, which presumably makes it difficult to adequately address the concerns presented in Box 1. In addition to the ideas discussed in Box 1, our presented analogy incorporates our previous research related to student challenges with enzyme kinetics.6 In order to keep the analogy simple and to narrow its scope, we focus specifically on supporting students in distinguishing between the different types of enzyme inhibition (competitive, noncompetitive, and uncompetitive). As discussed by Rodriguez and Towns,6 students tended to have difficulty differentiating between noncompetitive and uncompetitive inhibition due to the similarly sounding names, but students tended to have a clear understanding of the mechanism associated with competitive inhibition. As will be seen in the analogy presented, we take advantage of the intuitively named competitive inhibitor (the name suggests its mechanism, “the inhibitor competes for the active site”) to situate our analogy and serve as a basis to describe the other inhibition types. As another important consideration for our analogy, we avoided violent contexts (e.g., a child dying or cutting the head off an animal), and we suggest instructors do the same in their

analogies, since normalizing violence is not productive for fostering equity in learning environments. Competing for the Prize

The premise of our narrative-based analogy is a race with different runners competing, in which the runners each play by their own set of rules to cross the finish line, represented by the black and white checkerboard pattern, and win the prize. A summary of the analogy is provided in Figure 1 and is also provided as a separate file in the Supporting Information; instructors are encouraged to download this file and use it as part of their teaching (e.g., insert it into a PowerPoint presentation). In our analogy, “winning the prize” is analogous to an inhibitor binding the enzyme, and the “rules” each inhibitor plays by reflect the particulate-level mechanism: a competitive inhibitor only binds the free enzyme (i.e., has to reach the finish line before substrate); a noncompetitive inhibitor binds the free enzyme or the enzyme−substrate complex (i.e., can reach the finish line before or after the substrate); and an uncompetitive inhibitor only binds the enzyme−substrate complex (i.e., has to reach the finish line after the substrate). 1405

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ACKNOWLEDGMENTS We wish to thank Kinsey Bain, Brittland DeKorver, and the Towns research group for their support and helpful comments on the manuscript.

The analogy presented would be incomplete if its limitations were not addressed. For example, this analogy is distinct from other analogies discussed in this work and does not address the variety of enzyme kinetics ideas presented in Table 1, nor does it nicely map onto the “enzyme−substrate−catalytic event” pattern presented in Table 1; however, the competition analogy was not designed to be an “ultimate analogy” that encompasses everything. On the contrary, the analogy was intentionally limited for the sake of simplicity in order to target a particular challenge associated with nomenclature in enzyme kinetics. Therefore, how an inhibitor influences kinetic parameters, or a qualitative description of these kinetic parameters is not addressed in this analogy, along with other ideas, such as the influence of concentration, temperature, and pH; moreover, although the analogy is contextualized using a race, which may evoke ideas related to speed or velocity, the intention is not to focus on concepts related to reaction velocity or Vmax. The relationship between the analog and target domain is further clarified in Figure 2.

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CONCLUSION The intent of this work was not to evaluate the published analogies, but to consider what enzyme kinetics analogies were presented in the literature and contribute to this growing library of analogies to provide a simple, narrative-based analogy that instructors can discuss with students to help distinguish the different inhibition types. As discussed by Orgill and Bodner,3 analogies used to describe enzyme kinetics are less common in biochemistry textbooks, and surveying the analogies presented in the literature, none of the analogies addressed the issue of nomenclature conflation in enzyme kinetics. Most analogies focused on features such as competitive inhibition (a concept determined to be less challenging for students), whereas fewer focused on uncompetitive inhibition (a concept determined to be more challenging for students).6 We encourage instructors to make use of the analogy discussed herein and use the previously discussed features to develop their own analogies that are intentional, familiar, simple, clear, and bounded to help students understand complex ideas. As discussed by Asimov,8 “Metaphor, then by way of both reason and psychology, is itself a catalyst. By its mere presence and without actually increasing the scientific content of a course, it hastens the process of learning and is not used by thereby.” ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available on the ACS Publications website at DOI: 10.1021/acs.jchemed.9b00004. Image of Figure 1 for instructional use (PDF) Image of Figure 2 for instructional use (PDF)

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REFERENCES

(1) Ausubel, D. P. A Subsumption Theory of Meaningful Verbal Learning and Retention. Journal of General Psychology. 1962, 66 (2), 213−224. (2) Orgill, M.; Bussey, T. J.; Bodner, G. M. Biochemistry Instructors’ Perceptions of Analogies and Their Classroom Use. Chem. Educ. Res. Pract. 2015, 16 (4), 731−746. (3) Orgill, M.; Bodner, G. M. An Analysis of the Effectiveness of Analogy Use in College-Level Biochemistry Textbooks. J. Res. Sci. Teach. 2006, 43 (10), 1040−1060. (4) Orgill, M.; Bodner, G. What Research Tells Us About Using Analogies to Teach Chemistry. Chem. Educ. Res. Pract. 2004, 5 (1), 15−32. (5) Orgill, M.; Bodner, G. Locks and Keys: An Analysis of Biochemistry Students’ Use of Analogies. Biochem. Mol. Biol. Educ. 2007, 35 (4), 244−254. (6) Rodriguez, J.-M. G.; Towns, M. H. Analysis of Student Reasoning about Michaelis-Menten Enzyme Kinetics: Mixed Conceptions of Enzyme Inhibition. Chem. Educ. Res. Pract. 2019, 20 (2), 428−442. (7) Rodriguez, J. G.; Bain, K.; Towns, M. H. Graphs as Objects: Mathematical Resources Used by Undergraduate Biochemistry Students to Reason About Enzyme Kinetics. In It’s Just Math: Research on Students’ Understanding of Chemistry and Mathematics; ACS Symposium Series; American Chemical Society: Washington, DC, 2019; Vol. 1316, 6980. (8) Asimov, I. Enzymes and Metaphor. J. Chem. Educ. 1959, 36 (11), 535. (9) Abel, K. B.; Halenz, D. R. Enzyme Activity: A Simple Analogy. J. Chem. Educ. 1992, 69 (1), 9. (10) Hinckley, G. A Method for Teaching Enzyme Kinetics to Nonscience Majors. J. Chem. Educ. 2012, 89 (9), 1213−1214. (11) House, C.; Meades, G.; Linenberger, K. J. Approaching a Conceptual Understanding of Enzyme Kinetics and Inhibition: Development of an Active Learning Inquiry Activity for Prehealth and Nonscience Majors. J. Chem. Educ. 2016, 93 (8), 1397−1400. (12) Junker, M. A Hands-On Classroom Simulation To Demonstrate Concepts in Enzyme Kinetics. J. Chem. Educ. 2010, 87 (3), 294−295. (13) Lechner, J. H. More Nuts and Bolts of Michaelis-Menten Enzyme Kinetics. J. Chem. Educ. 2011, 88 (6), 845−846. (14) Murkin, A. S. Commentary: Ohm’s Law as an Analogy for Enzyme Kinetics: Commentary: Ohm’s Law as an Analogy for Enzyme Kinetics. Biochem. Mol. Biol. Educ. 2015, 43 (3), 139−141. (15) Ochs, R. S. Understanding Enzyme Inhibition. J. Chem. Educ. 2000, 77 (11), 1453. (16) Silverstein, T. P. Breaking Bonds versus Chopping Heads: The Enzyme as Butcher. J. Chem. Educ. 1995, 72 (7), 645. (17) Silverstein, T. The Nuts and Bolts of Michaelis-Menten Enzyme Kinetics: Suggestions and Clarifications. J. Chem. Educ. 2011, 88 (2), 167−168. (18) Runge, S. W.; Hill, B. J. F.; Moran, W. M. A Simple Classroom Teaching Technique To Help Students Understand MichaelisMenten Kinetics. LSE 2006, 5 (4), 348−352. (19) Helser, T. L. Enzyme Activity: The Ping-Pong Ball Torture Analogy. J. Chem. Educ. 1992, 69 (2), 137.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Jon-Marc G. Rodriguez: 0000-0001-6949-6823 Marcy H. Towns: 0000-0002-8422-4874 Notes

The authors declare no competing financial interest. 1406

DOI: 10.1021/acs.jchemed.9b00004 J. Chem. Educ. 2019, 96, 1401−1406