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Student Centered Education The Polygonal Model: A Simple Representation of Biomolecules as a Tool for s Teaching Metabolismw
Carlos Francisco Sampaio Bonafe †* Jose Ailton ~o Bispo‡ Conceic¸a Marcelo Bispo de Jesus†
From the †Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Campinas, SP, 13083-970, Brazil, ‡Department of Technology, Faculty of Food Engineering, University of Feira de Santana (UEFS), CP 252/294, Feira de Santana, BA, 44036-900, Brazil
Abstract Metabolism involves numerous reactions and organic compounds that the student must master to understand adequately the processes involved. Part of biochemical learning should include some knowledge of the structure of biomolecules, although the acquisition of such knowledge can be time-consuming and may require significant effort from the student. In this report, we describe the “polygonal model” as a new means of graphically representing biomolecules. This model is based on the use of geometric figures such as open triangles, squares, and circles to represent hydroxyl, carbonyl, and carboxyl groups, respectively. The usefulness of the polygonal model was assessed by undergraduate students in a classroom activity that consisted of “transforming” molecules from Fischer models to polygonal models and vice and versa. The survey was applied to 135 undergraduate
Biology and Nursing students. Students found the model easy to use and we noted that it allowed identification of students’ misconceptions in basic concepts of organic chemistry, such as in stereochemistry and organic groups that could then be corrected. The students considered the polygonal model easier and faster for representing molecules than Fischer representations, without loss of information. These findings indicate that the polygonal model can facilitate the teaching of metabolism when the structures of biomolecules are discussed. Overall, the polygonal model promoted contact with chemical structures, e.g. through drawing activities, and encouraged student-student dialog, C 2017 by The thereby facilitating biochemical learning. V International Union of Biochemistry and Molecular Biology, 46(1):66–75, 2018.
Keywords: Biomolecule representations; polygonal model; visual literacy
Introduction “Education is the kindling of a flame, not the filling of a vessel.” Socrates
Volume 46, Number 1, January/February 2018, Pages 66–75 *To whom correspondence should be addressed. E-mail: bonafe@ unicamp.br. w s Additional Supporting Information may be found in the online version of this article. Received 17 January 2017; Revised 6 September 2017; Accepted 13 October 2017 DOI 10.1002/bmb.21093 Published online 13 November 2017 in Wiley Online Library (wileyonlinelibrary.com)
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Biochemistry is central to understanding biological processes, yet its intrinsic complexity makes it a difficult subject for teachers and students [1]. A correct understanding of biochemistry, particularly metabolic pathways (and metabolism in general), requires a solid foundation in physics, chemistry, and biology. Metabolism is particularly difficult for students to master because of the numerous reactions involved, as well as the need to understand the overall significance of the different pathways and their physiological roles in the organism. In addition, metabolic pathways have several key steps involving allosteric or covalently modulated regulation and are often located in different cellular compartments. A common dilemma for teachers is how much of the chemical structure of the compounds involved should be taught to and required of students. Undoubtedly, a minimal knowledge of chemical structures is necessary to
Biochemistry and Molecular Biology Education
understand biological phenomena at a molecular level [1–8]. On the one hand, knowledge of all biomolecular structures of all metabolic pathways is an unrealistic scenario since it would demand too much student time and effort, thereby destroying the beauty of biochemistry. Clearly, these two extreme situations are undesirable. Rather, we should foster the students’ visual literacy [9, 10]. The development of representational skills is mandatory in learning chemistry and is part of the process of moving from novice to expert [6, 8–15]. The conceptual understanding of chemical representations is a longstanding problem [5, 7, 11–15]. To help students comprehend structural chemistry, various external representations have been proposed, including dynamic visualizations [1, 2, 5, 8, 16], representation platforms [1–8], and augmented reality [5, 7, 11–15, 17]. Different representations corresponding to scientific or teaching models can be used, depending on the situation [15, 18]. Students may be confused when new models are introduced or when the attributes of different models are combined [11, 15, 19]. Certainly, the skills required for reading and writing a visual or symbolic language, i.e. visual literacy, are broadly needed when teaching and learning biochemistry, as well as for the structural manipulation of molecules. Hence the importance of having several alternatives for teaching and understanding molecular structures from various perspectives and depth [1, 8, 19]. Such models can be used to complement the learning process, as long as the advantages and limitations of each model are fully recognized [3, 6]. For this reason, teachers require training in the correct use of new tools, although this is an area that is typically neglected in research [7, 11, 14]. Biochemistry is offered in several undergraduate courses and frequently involves students with very diverse backgrounds, as well as considerable variation in the goals to be reached and the duration of the course. Regardless of the specific course involved, it is important to ensure adequate learning of biochemistry. In metabolism, biomolecules undergo many sequential transformations involving numerous biochemical structures, even when only a few metabolic pathways are considered. The tight schedule of some courses means that the time available for teaching metabolism to students who sometimes do not possess enough knowledge in organic chemistry is often quite limited. In this context, biochemistry teachers expect students to learn the structures of key biomolecules and metabolites [20]. The question then is how to make the best use of the available time, how to get the students involved with molecules, and how to convey a volume of information that is often cold, abstract, and static, while at the same time preserving the students’ motivation for learning about metabolism. Although several approaches for teaching the chemical structures of molecules involved in metabolism have been suggested [1–15], in this report, we propose a new way of
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FIG 1
Fischer projection of the open-chain form of glucose (A) compared to the polygonal model (B). (C) and (D) show the corresponding representations of the b isomer of cyclic glucose, i.e. b-Dglucopyranose. Organic groups and their respective representations: carbonyl (ACOH): squares, hydroxyl (AOH): triangles. All figures were drawn using the software Python (version 3.2) and the module Pygame.
representing compounds involved in metabolism, with the suppression of details for the sake of simplicity. In addition, alternative models provide additional tools that can stimulate student learning [15]. The scheme allows visualization of details of the reactions and metabolic pathways and can be useful for stimulating deeper discussion. Such a simplified representation allows rapid familiarization and understanding by the student, thereby improving the learning process. In addition, this model encourages students to look at underlying assumptions that are embedded in classic representations, i.e. Fischer projections. Thus, the aims of this work were to provide a simple way of representing biomolecules and to foster the development of representational competence by stimulating the students to learn how to switch between the proposed model and Fischer representations.
Biomolecules in a Simpler Perspective For the sake of comparison, we represent the open form of glucose in a classic Fischer projection (Fig. 1A) side by side with the polygonal model. Here, open triangles represent hydroxyl groups (AOH) and squares represent carbonyl groups (C@O), all of which are bound to a carbon skeleton represented by a vertical line. Hydrogens have been omitted for simplicity. Groups bound to asymmetric carbons are depicted by horizontal lines and those to nonasymmetric carbons as sloped or inclined lines. For example, Fig. 1B shows that glucose possesses four asymmetric carbons. The corresponding closed forms of glucose that predominant in solution are shown in Figs. 2C and 2D. Geometric shapes, i.e. polygons, were chosen to represent the main chemical groups, e.g. hydroxyls and carbonyls. This oversimplification of using familiar shapes to represent chemical
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Biochemistry and Molecular Biology Education
FIG 2
Polygonal model representation of (A) the conversion of methane to carbon dioxide by oxidation, an energetically favorable process in metabolism, and (B) glycolitic pathway in which only the initial, intermediate and final molecules are represented. The hydroxyls and carboxyls coupled to phosphate groups maintain their normal symbols in this model as a means of stimulating student discussion (see text for details). [Color figure can be viewed at wileyonlinelibrary.com]
structures is an informal approach intended to encourage students to critically analyze chemical structures [21]. Next, we show that the glycolytic pathway can be represented using the polygonal model (Fig. 2), in which the carboxyl groups (COOH or COO2) are depicted as circles, the phosphate groups as yellow circles with a “P” inside, and an additional line represents a double bound, e.g. phosphoenolpyruvate. In some cases, for clarification, carbons are depicted as small closed circles, e.g. pyruvate, in which some carbons are bound only to carbon and hydrogen atoms. For simplicity, some coenzymes and other participants of metabolic pathways are not represented [22]. The polygonal model may increase students’ awareness of certain aspects of chemical modifications. For example, it is easy to appreciate the reduction of pyruvate to lactate just by noting the change from a carbonyl to a hydroxyl group that is promptly visualized as a switch from a square to a triangle. The same can be said about oxidation, hydration, phosphorylation, and other chemical changes. In
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addition, asymmetric carbons are easily spotted as horizontal lines, as already mentioned. This approach makes it easy to identify the three intermediates (dihydroxyacetone phosphate, phosphoenolpyruvate, and pyruvate) in anaerobic glycolysis (from glucose to lactate) that have no asymmetric carbon; this identification often takes longer when the students have to examine the Fischer projections of the glycolytic intermediates. The polygonal model can easily be extended to other metabolic pathways, such as the Krebs (citric acid) cycle (Fig. 3). After familiarization with the model, it is easy to identify the steps involving oxidation, decarboxylation, hydration, dehydration or condensation. In this context, the model can be used to compare the last steps of the Krebs cycle and fatty acid b-oxidation (Lynen cycle) to reveal the remarkable similarities in their chemical structures (Fig. 4). Both processes occur in mitochondria and in each oxidation-reduction reaction the same coenzyme is used (FAD in the first and NAD1 in the fourth). The participation
The Polygonal Model
FIG 3
The Krebs cycle represented using the polygonal model. Only intermediate molecules are represented. See Fig. 2 for symbol definitions. The blue groups correspond to the carbons from acetyl-CoA. [Color figure can be viewed at wileyonlinelibrary.com]
of FAD in the oxidation of succinate and acyl-CoA in the Krebs cycle and b-oxidation, respectively (Fig. 4, reactions R1), can be explained by the relatively low reduction
FIG 4
Bonafe et al.
Polygonal representation of the first steps of fatty acid b-oxidation (Lynen cycle) compared with the Krebs cycle. Only the intermediates are represented. See Fig. 2 for symbol definitions. In R1 reactions, FAD is reduced to FADH2 while in R2 reactions H2O is introduced and in R3 reactions NAD1 is reduced to NADH 1 H1. [Color figure can be viewed at wileyonlinelibrary.com]
potential of the electrons since they are directly bound to saturated carbons in the hydrocarbon chain. In contrast, the electrons from carbons linked to hydroxyls have enough reducing potential to use NAD1, which explains why this coenzyme is employed in R3 reactions. In addition, Fig. 4 shows the formation of the trans isomer in both metabolic pathways, which results from the first oxidation step of these pathways furnishing fumarate (R1 reaction) and trans enoyl acyl-CoA (R’1 reaction). This way of representing the trans forms demonstrates the visual capacity of the polygonal model to convey structural details and helps to explain similar enzyme activities [20]. Thus, this model could be a useful starting point for further discussions and for stimulating questions regarding metabolism and enzymatic activity. In addition, thinking about external representations can help students to develop their visual literacy [9, 15] The polygonal model can also be used to represent other biomolecules, such as amino acids. For this, the amino group is represented by a blue closed circle, the amide group as a carboxyl and amide combination, the sulfhydryl group as a yellow triangle, and the phenyl group as a circle sectioned diagonally to represent aromatic amino acids. The amino acids valine, isoleucine, leucine, and methionine can be easily recognized because of the hydrocarbon chains, in contrast to other amino acids that have hydroxyl or charged R groups (Fig. 5B). Alternatively, as shown in Fig. 5, polygonal structures can be represented by black and white figures with no loss of information or visual effect. In this case, the thiol group was changed from a yellow to a white triangle containing the letter S and the amino group was changed from a blue to a gray circle. In this way, students can easily represent molecules in a simple fashion using a pen or pencil and a piece of paper. The use of this external representation allows students to become familiar with the structures of metabolic mole€nborn and Anderson, visual cules. As suggested by Scho literacy, particularly in biochemistry, involves mastering several cognitive skills, such as decoding the symbolic language encapsulated in external representations, evaluating the power, limitations and quality of external representations, constructing an external representation to explain a concept or solve a problem, translating horizontally across multiple external representations of a concept, and interpreting and using external representations to solve a problem. In this context, we proposed a classroom activity that explored these five cognitive skills, which are part of eight skills considered previously [22]. When being taught metabolism, students should be encouraged to expand their knowledge. This includes thinking critically about basic concepts and developing transferable skills, rather than passively receiving information from instructors [4, 6, 7]. In this context, the polygonal model may help students to focus on fundamental aspects rather than on unnecessary details, although the model is
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Biochemistry and Molecular Biology Education
FIG 5
Keto acids and amino acids represented using the polygonal model. (A) Glycine, alanine, serine, phosphoserine, cysteine, and threonine. (B) Valine, isoleucine, leucine, and methionine. (C) Glycine, alanine, serine, phosphoserine, cysteine, and threonine, black and white version, (D) Phenylalanine and tyrosine. (E) Oxaloacetate, aspartate, and asparagine. (F) aKetoglutarate, glutamate, and glutamine. (G) Lysine and arginine. [Color figure can be viewed at wileyonlinelibrary.com]
not intended to replace Fischer projections. The applicability of the polygonal model was assessed by using it to teach biochemistry to undergraduate Biology and Nursing students.
amount of prior conceptual knowledge, e.g. a working knowledge of Fischer projections and basic concepts of organic chemistry [22], in order for the students to interpret the polygonal model. To evaluate the introduction of this external representation, the classroom activity was structured as indicated below.
Procedures
Introducing the Polygonal Model
A classroom activity involving the polygonal model was applied to Biology (n 5 95) and Nursing (n 5 40) students. The setting for this task was the students’ initial classes on metabolism in the biochemistry module of their respective courses. The activity was designed to require a minimal
The students received an introduction that consisted of a one-page explanation of the polygonal model in which some molecules represented by this model and Fischer projections were compared (Supporting Information Fig. S1). This part of the activity lasted about 15 min, during which
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The Polygonal Model
The number and percentage of molecules that presented errors and a description of the most prevalent errors when transforming Fisher representations of Krebs cycle intermediates and acetyl CoA into the polygonal model
TABLE I
Biomolecule
Number of errors
%
Acetyl CoAa
10
9.0
Representation of an additional group in acetyl
9
7.8
Change in the groups bound to the main chain
7
5.9
Absence of double bond representation
Isocitrate
21
19.3
Change in the position of groups bound to the main chain; change in the position of the groups bound to the chiral carbon
Oxalosuccinate
36
32.7
Representation of the carbonyl carbon group extending out from the carbon chain
a-Ketoglutarate
28
25.0
Representation of the carbonyl carbon group extending out from the carbon chain
Succinyl CoAa
28
25.5
Representation of the carbonyl carbon group extending out from the carbon chain
Succinate
3
2.8
Lack of representation of carbons 2 and 3.
Fumaratec
10
9.3
Inadequate or absent representation of the double bond in the carbon chain
Malate
15
13.2
Inadequate placement of the hydroxyl group; lack of hydroxyl group
Oxaloacetate
22
20.2
Representation of the carbonyl carbon group extending out from the carbon chain
Citrate
b
Cis-aconitate
a
Most students considered the thioester group as carbonyl (not computed here as an error, see text).
b
c
b
Most prevalent errors
Most students failed to represent the third carbon as not asymmetric (not computed here as an error).
Most students did not represent fumarate as a trans isomer (not computed here as an error).
Items that were left unanswered (8.9%) were not computed here. Fig. 3 shows the forms considered to be correct. The molecules are listed in the order in which they appear in the Krebs cycle. Number of participants: 83 Biology and 36 Nursing students.
time the students were free to ask questions and discuss the topic with the instructors. The analysis was based on the percentage of right answers, the type and frequency of errors and whether they were related to misconceptions of organic chemistry, confusion among different organic functional groups, or distractions.
Classroom Context and Data Collection After the initial familiarization, the students undertook an exercise that involved converting the Krebs cycle molecules from Fischer projections to the polygonal model. Subsequently, the students were asked to convert an additional
Bonafe et al.
four molecules from the polygonal model to Fischer projections (Supporting Information Figs. S2 and S3). This part and the previous one lasted 35 min. In both activities, the students were allowed to keep the introductory material for future consultation. The analysis was also based on the answers and the type of errors, such as the erroneous classification of a molecule using the polygonal model or a lack of foundation in organic chemistry. In converting Fischer projections to the polygonal model the frequency of misrepresentation for each molecule of the Krebs cycle was recorded (Table I), while for conversion from the polygonal model to Fischer projections, the total number of errors was recorded, regardless of whether this involved
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Biochemistry and Molecular Biology Education
TABLE II
Most frequent errors detected during the transformation of polygonal model representations into the Fischer model for the molecules mevalonate, ribose-5-phosphate, sedoheptulose 7-phosphate and a-ketoadipate (see Supporting Information Fig. S3)
Type of error Omission of carbons in the carbon chain* Lack or excess of hydrogen bonds in carbon** 2PO22 3 **
Number of errors
%
40
27.4
33
22.6
10
6.85
Oxygen with three bonds**
9
6.16
Excess of carbon in the carbon chain*
7
4.79
Change of CAOH to C@O, and vice versa*
7
4.79
Absence of a methyl group (mevalonate)*
6
4.11
Absence of the OH or O group (in CAOH or C@O)*
6
4.11
Change or omission of other groups*
5
3.42
Change of C to O in the carbon chain**
5
3.42
Change in the spatial arrangement of the group in asymmetric carbon*
4
2.74
Change of phosphate to S-CoA**
1
0.68
Change of C@O to CO2**
1
0.68
146
100
Inadequate representation of the phosphate group as
Total
The errors were attributed to the inadequate use of the rules of the polygonal model (*) and a lack of foundational knowledge in organic chemistry (**). Students who did not participate in the activity (N 5 14) were not computed here. In some case, more than one error was associated with the same molecule. Number of participants: 83 Biology and 36 Nursing students.
the same molecule (more than one error per molecule) or different molecules (Table II).
Opinion Survey and Analysis After the activities, the students were surveyed for their opinions about the (1) advantages, (2) limitations and (3) applications of the polygonal model relative to Fischer projections (Table III), in an approach similar to that used in other studies [23, 24]. This survey sought to evaluate the students’ receptivity and feelings toward the polygonal model. The analysis was scored based on the frequency of replies, namely, >60%, 30–60%, and 80%) of these errors involving chirality and representation of the CoA thioester bond could be used as a diagnostic tool; for this reason, neither of these cases was computed as an error in Table I.
The Polygonal Model
TABLE III
Students’ opinions regarding the advantages and limitations of the polygonal model compared to Fischer projections
Fischer
Polygonal
Advantages
More detailed; good for studying reactions in detail, for designating specific hydrogen atoms, for direct visualization of structures; applicable to any molecule; visualization of charges.
More schematic, simpler, easier, and faster to write*; easier to visualize and memorize, organize and identify chemical groups*; more compact. Provides a quicker idea of the chemical groups involved; easier and faster to visualize chiral carbons, easier to compare similar molecules and specific changes in reactions (i.e. good for metabolic pathways); there is no loss of structural information; visually aesthetic, more didactic
Limitations
More complex, sometimes confusing; harder to manipulate, bulky, visually more “polluted”
Requires training prior to use, requires a legend to decode the symbols, does not show the charge of molecules, is less universal, ‘less accurate’
Applications
For studying reaction mechanisms; allows detailed representation of molecules
Useful for displaying long chains of reactions (such as in metabolic pathways)* and for displaying biomolecules in less detail
Nonbold opinions: 60% of student responses. Comments indicated in bold were the most prevalent. Number of participants: 83 Biology and 36 Nursing students.
The most common error (>15%) involved representation of the carbonyl group extending out from the carbon chain, as if it were “5O” instead of “-C 5 O” (Table I). Less common errors (
