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Use of general principles in teaching biochemistry
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Use of General Principles in Teaching Biochemistry ROLANDO HERNANDEZ FERNANDEZ and AGUSTIN VICEDO TOMEY
Department of Biochemistry Higher Institute of Medical Sciences Havana, Cuba Introduction Biochemistry has been taught mainly by means of detailed descriptions of chemical structures and reactions, but today the body of knowledge surrounding this discipline is so vast that this way of teaching has become impractical. It is necessary to develop new, rational methods for teaching this subject, keeping in mind (a) the students' need for knowledge, (b) the constant and indeed exponential increase in new information, (c) the limited time for teaching it, and (d) the need of students, as well as of teachers to have a point of view by which they can get to grips with a large amount of knowledge. During the last five years, our department has been engaged in the development of a general aspect of defining biochemical knowledge and we have found it particularly useful for teaching medical students. These 'generalizations' have been defined as categories, concepts, principles, models and guiding ideas. We present here these Principles of Biochemistry, as a generalization of the principal traits of the object of study of this science. In the initial stages of their study students do not know the content of the course, and thus we do not present these principles all together, but rather one by one, at the points when the stage of study allows them to be better understood. We subsequently ask the students for the application of each principle on an appropriate occasion. Thus, each principle is presented to the students in relation to different themes, for instance, Principles Nos 2 and 3 (see below) are dealt with in relation to Macromolecules, No 5 in relation to Biocatalysts, and so forth. We evaluate how the students understand and apply each principle in seminars, laboratories and, of course, in the final examination, when it is expected that students should be at the peak of their training. We have been using this approach during the last five years not only in our department but also in 17 Faculties of Medicine in our country that have adopted this method. Judging by the results obtained, we believe this strategy to be correct, although obviously any competent professor might obtain similar results using another approach. We list below the proposed Principles of Biochemistry with a brief comment on each.
(1) The Principle of Continual Turnover The continual interchange of substances, energy and information with the environment is one of the main characteristics of living things, reflecting their dynamic state. This is the conceptual content of this principle. By means of this interchange, the living organism replaces all B I O C H E M I C A L EDUCATION 19(4) 1991
its cellular components, from the simplest molecule to the most complex organelle. Independently of the speed and the mechanisms by which this replacement is brought about, each component of living matter has only a transitory existence. In analyzing any metabolic process, students ought to realize that the compounds involved are in constant flux as a consequence of synthesis and breakdown. For example, liver glycogen is being continuously renewed and at any given moment, its level is the result of the relative activities of the processes of glycogenogenesis and glycogenolysis.
(2) The Principle of Macromolecular Organization Macromolecules are the most important components of living matter, all of them are constructed by polymerization of low molecular weight precursors, all of similar structure, joined together by covalent bonds. In all macromolecules one can distinguish a constant region and a variable one. Between these two different regions or domains, interactions take place. When elements of the constant zone are involved, regular structures will arise, but when interactions take place within the variable region, more or less irregular structures are formed depending upon the variability of the precursors. This may be illustrated as follows. In protein molecules one can distinguish a region formed by successive peptide bonds. The structure of this zone is the same in all proteins, varying only in length; therefore, this is the constant region. The distribution of amino acid side chains, however, is different in every protein, and so this is referred to as the variable region. The structures resulting from the interactions (hydrogen bonds) within the constant region are fairly regular and fall into two broad classes: s-helical and 13-sheet structures. Conversely, if interactions take place between side chain residues, an irregular structure is obtained which determines protein shape. We observe similar regularities in polysaccharide and nucleic acid structures. These regularities appear and express themselves in variable degree in different kinds of macromolecules, a fact that students must keep in mind when they analyze composition-conformation-function relationships.
(3) The Principle of Molecular Recognition In contrast to inorganic chemistry, biochemical phenomena take place via highly specific interactions between two or more molecules. This high degree of specificity is achieved because macromolecules with a highly organized structure and shape are involved in these interactions. This characteristic of biochemical systems is summarized by stating that, independently of what follows, biochemical events always begin with mutual specific recognition between molecules, and at least one of these will be a macromolecule. From this beginning, it is possible to explain catalysis, hormone action, allosteric regulation, etc. In molecular recognition, specificity relies upon steric complementarity and multiple weak bonds.
183
(4) The Principle of Multiplicity of Utilization Most of the compounds present in living organisms, especially those of low molecular weight, may be used in several ways according to the reaction possibilities of their structures. Certain substances (eg glucose) may be catabolized to produce energy, polymerized to produce structural macromolecules or converted into stored reserves. In considering any biochemical substance, the student should realise that most likely this compound has more than one function in the organism. (5) The Principle of Maximum Efficiency In living systems, almost all transformations depend on the action of biocatalysts. These catalysts have a high degree of specificity and, in addition, each reaction produces a very high proportion of 'desired' product molecules from the substrate with few secondary products. This high efficiency results from the specificity of the biocatalysts, their mechanisms of action, their subcellular localizations and the way in which they are organized. This allows the organism to carry out any given biological function using only the necessary and sufficient quantity of substance, energy and information, because metabolic pathways are under tight regulatory central mechanisms commonly effected by feedback loops by which substrates or products act upon one of the first reactions of a pathway. These regulatory mechanisms control the direction and extent of metabolic processes, allowing their constant adaptation to an organism's needs at any moment. (6) The Principle of Gradual Changes Transformations take place by metabolic pathways and cycles integrated by a variable number of enzymecatalyzed reactions. In each of these reactions, a gradual transformation of substrate occurs by addition or subtraction of chemical groups, linkage formation or breakdown, transformation of functional groups, and so on. As a rule, no great change takes place in the general structure of the substance or in its energetic content in a single step. Of course, the cumulative effect of all these minor changes ultimately gives rise to the major transformations that take place in metabolic pathways. Thus, the purine nucleotide biosynthesis pathway has no less than thirteen enzyme-catalyzed reactions. (7) The Principle of Interrelationship Living organisms are complex systems in which each structural and functional component is directly or indirectly connected with the rest. There is no isolated metabolic process; all of the metabolic pathways are more or less tightly related to each other. This characteristic is a result of the requirements for substances, energy or information needed for normal functioning of metabolic processes, which must be obtained from other processes or directly from the environment. At the same time, each biochemical process B I O C H E M I C A L EDUCATION 19(4) 1991
generates products that are needed by other pathways and other organisms. The utilization of substances, energy or information coming from other processes, that establish and maintain these special links among biochemical processes, is a general regularity observed in metabolism. The Cori cycle is a good example.
(8) The Principle of Transformational Reciprocity In biochemical transformations, it usually happens that if a substance A can be converted into another substance H, the reciprocal transformation of H into A is possible (and indeed probable). Although this event may occur by direct inversion of the transformation when single reactions are involved, in the case of more complex pathways, the reciprocal transformations always take place via different routes, at least for some of the steps. There are two important consequences of this situation. First, these complex biochemical processes are not controlled by the Law of Mass Action, and second, the 'differential' steps are commonly targets for the regulatory mechanisms. The biosynthesis of glucose proceeds in large part by a reversal of a number of enzymatic reactions, but it differs from glycolysis at the two critical points in the whole sequence, that is, at either end. Only in the synthesis of very specific compounds does this rule not hold. (9) The Principle of Information Transfer Living organisms are characterized by a very high degree of structural and functional organization. Perpetuation of this order is an unavoidable requisite for life to continue. In this perpetuation, molecular information, sequential or conformational, plays the major role. Basic mechanisms dealing with information in living matter follow certain regularities; whatever the steps or mechanisms involved, molecular information flows from molecules in which sequential information predominates to molecules in which conformational information is more relevant. Thus, 'everything' that a cell can do is stored in a linear sequence of nucleotides in DNA (sequential information) but cells cannot do anything unless previous synthesis of proteins (conformational information) occurs, in which process the flux stated in the principle is taking place. Conclusions Our experience is that the introduction of these principles in teaching Biochemistry to medical students is very rewarding. Students are able to understand, provided they learn the principles, the general characteristics of biochemical processes, even if they have never seen a particular pathway before. In confronting a new metabolic process, they have to learn some particular details but they are correctly oriented from the beginning with general rules that are reinforced continuously. In this way, learning is easier and fundamental knowledge is better understood and retained. Students are also better prepared for future self-education.
184 At the same time teachers do their work in a more systematic way, because they must first explain and demonstrate the principle with a few examples. What remains is mainly to work together with students in their application in a very active interaction in such a way that the new knowledge becomes more firmly established. This teaching strategy also simplifies the planning and development of academic activities, including lectures, seminars and laboratories. In our current program, the use of these Principles of Biochemistry is complemented by other generalizations such as categories, concepts, models and guiding ideas, which together constitute a useful set of didactic tools in teaching Biochemistry.
Learning from Failures MURRAY SAFFRAN
Department of Biochemistry and Molecular Biology Medical College of Ohio Toledo, Ohio 43699, USA Introduction This journal and other educational journals contain many papers that describe innovative teaching successes. The innovative programmes are evaluated by questionnaires and the students usually favour their experience by a statistically significant margin. Rarely are teaching failures described in the literature, yet I am sure that many attempts at innovations in education are unsuccessful. Can we learn from our failures? I was asked to teach the section on Nutrition and Digestion in the medical biochemistry course. In the past it was a topic that received only mild attention from the students, yet it is of great importance to the practising physician. Was it possible to stimulate more interest in Nutrition and Digestion on the part of our future physicians? We decided to try. Nutrition and Digestion We changed the schedule to bring together the lecture hours devoted to digestion by the departments of Biochemistry and Physiology, giving us a block of 2 weeks to devote to the topic. Then we gathered a team of experts in Nutrition and Digestion to outline the course. We have had previous successful experiences with group learning in student-run courses; 1'2 we agreed that the students should be able to teach the course themselves because the topics, although important in medicine, were relatively easy to understand. The medical class of about 140 students was divided into 20 groups. Each group was assigned an hour to present a section of the course. Each group would gather the information and relay it to the rest of the class in whatever way they deemed best. We encouraged the students to go beyond the lecture format in their presentations. BIOCHEMICAL
E D U C A T I O N 19(4) 1991
Seeing the Error of our Ways In retrospect, the course failed because of a series of mistakes on our part. Mistake number 1 was to tell the class about the course through class representatives, instead of meeting with the entire class. We had decided to use the channel of the class officers for a valid reason - - to spare the entire class the time of a meeting. However, the class felt that we should have met with all of them face-to-face because the class representatives were unable to answer questions that arose. Mistake number 2 was our failure to assess the receptivity of the class to a different format of teaching. This class was already angered by the perceived imposition of a new series of comprehensive examinations, replacing those on the original timetable. The students regarded the timetable as a sacred contract between them and the curriculum and any deviation from it was breaking the contract. When we changed the timetable, the anger generated by the change in the examinations spilled over onto us. Mistake number 3 was to overestimate the maturity of the students. In our previous experiences with studentmanaged courses the students responded enthusiastically to the welcome change from the endless series of lectures. They felt that they could do better than their professors, and in some cases, they did do better. But this class was different. They objected to being asked to teach each other. They were paying fees so that professors would teach them, not untrained fellow students, who might tell them wrong facts, or omit important details. Our reassurances that we would monitor the presentations and correct and add to the presentations fell on deaf ears. The insecurity of being taught by non-experts was contagious. Even those students who were enthusiastic at first, were swept up by the wave of resentment. The students also believed that preparation and presentation of the course would take too much time away from their studies and that they would have to neglect other concurrent courses. Mistake number 4 was to encourage the students to develop their own list of course objectives. They were accustomed to receiving a long list of objectives from the lecturers. When we suggested that each group should write their own objectives, which we would then review and edit, the students felt that they needed guidance in the first stages, and not after they had developed a first draft. Mistake number 5 was our expectation that the students would consult us frequently during the development of the presentations. Only two or three groups did so. The rest ignored our offers of help. Mistake number 6 was our failure to cope with the problem of the large number of students who refused to participate in the course. The resentment of the students who did the work was directed not at their recalcitrant classmates but toward us. Mistake number 7 was our laissez-faire policy toward attendance at the presentations. About 1/5 to 1/3 of the
Use of General Principles in Teaching Biochemistry ROLANDO HERNANDEZ FERNANDEZ and AGUSTIN VICEDO TOMEY
Department of Biochemistry Higher Institute of Medical Sciences Havana, Cuba Introduction Biochemistry has been taught mainly by means of detailed descriptions of chemical structures and reactions, but today the body of knowledge surrounding this discipline is so vast that this way of teaching has become impractical. It is necessary to develop new, rational methods for teaching this subject, keeping in mind (a) the students' need for knowledge, (b) the constant and indeed exponential increase in new information, (c) the limited time for teaching it, and (d) the need of students, as well as of teachers to have a point of view by which they can get to grips with a large amount of knowledge. During the last five years, our department has been engaged in the development of a general aspect of defining biochemical knowledge and we have found it particularly useful for teaching medical students. These 'generalizations' have been defined as categories, concepts, principles, models and guiding ideas. We present here these Principles of Biochemistry, as a generalization of the principal traits of the object of study of this science. In the initial stages of their study students do not know the content of the course, and thus we do not present these principles all together, but rather one by one, at the points when the stage of study allows them to be better understood. We subsequently ask the students for the application of each principle on an appropriate occasion. Thus, each principle is presented to the students in relation to different themes, for instance, Principles Nos 2 and 3 (see below) are dealt with in relation to Macromolecules, No 5 in relation to Biocatalysts, and so forth. We evaluate how the students understand and apply each principle in seminars, laboratories and, of course, in the final examination, when it is expected that students should be at the peak of their training. We have been using this approach during the last five years not only in our department but also in 17 Faculties of Medicine in our country that have adopted this method. Judging by the results obtained, we believe this strategy to be correct, although obviously any competent professor might obtain similar results using another approach. We list below the proposed Principles of Biochemistry with a brief comment on each.
(1) The Principle of Continual Turnover The continual interchange of substances, energy and information with the environment is one of the main characteristics of living things, reflecting their dynamic state. This is the conceptual content of this principle. By means of this interchange, the living organism replaces all B I O C H E M I C A L EDUCATION 19(4) 1991
its cellular components, from the simplest molecule to the most complex organelle. Independently of the speed and the mechanisms by which this replacement is brought about, each component of living matter has only a transitory existence. In analyzing any metabolic process, students ought to realize that the compounds involved are in constant flux as a consequence of synthesis and breakdown. For example, liver glycogen is being continuously renewed and at any given moment, its level is the result of the relative activities of the processes of glycogenogenesis and glycogenolysis.
(2) The Principle of Macromolecular Organization Macromolecules are the most important components of living matter, all of them are constructed by polymerization of low molecular weight precursors, all of similar structure, joined together by covalent bonds. In all macromolecules one can distinguish a constant region and a variable one. Between these two different regions or domains, interactions take place. When elements of the constant zone are involved, regular structures will arise, but when interactions take place within the variable region, more or less irregular structures are formed depending upon the variability of the precursors. This may be illustrated as follows. In protein molecules one can distinguish a region formed by successive peptide bonds. The structure of this zone is the same in all proteins, varying only in length; therefore, this is the constant region. The distribution of amino acid side chains, however, is different in every protein, and so this is referred to as the variable region. The structures resulting from the interactions (hydrogen bonds) within the constant region are fairly regular and fall into two broad classes: s-helical and 13-sheet structures. Conversely, if interactions take place between side chain residues, an irregular structure is obtained which determines protein shape. We observe similar regularities in polysaccharide and nucleic acid structures. These regularities appear and express themselves in variable degree in different kinds of macromolecules, a fact that students must keep in mind when they analyze composition-conformation-function relationships.
(3) The Principle of Molecular Recognition In contrast to inorganic chemistry, biochemical phenomena take place via highly specific interactions between two or more molecules. This high degree of specificity is achieved because macromolecules with a highly organized structure and shape are involved in these interactions. This characteristic of biochemical systems is summarized by stating that, independently of what follows, biochemical events always begin with mutual specific recognition between molecules, and at least one of these will be a macromolecule. From this beginning, it is possible to explain catalysis, hormone action, allosteric regulation, etc. In molecular recognition, specificity relies upon steric complementarity and multiple weak bonds.
183
(4) The Principle of Multiplicity of Utilization Most of the compounds present in living organisms, especially those of low molecular weight, may be used in several ways according to the reaction possibilities of their structures. Certain substances (eg glucose) may be catabolized to produce energy, polymerized to produce structural macromolecules or converted into stored reserves. In considering any biochemical substance, the student should realise that most likely this compound has more than one function in the organism. (5) The Principle of Maximum Efficiency In living systems, almost all transformations depend on the action of biocatalysts. These catalysts have a high degree of specificity and, in addition, each reaction produces a very high proportion of 'desired' product molecules from the substrate with few secondary products. This high efficiency results from the specificity of the biocatalysts, their mechanisms of action, their subcellular localizations and the way in which they are organized. This allows the organism to carry out any given biological function using only the necessary and sufficient quantity of substance, energy and information, because metabolic pathways are under tight regulatory central mechanisms commonly effected by feedback loops by which substrates or products act upon one of the first reactions of a pathway. These regulatory mechanisms control the direction and extent of metabolic processes, allowing their constant adaptation to an organism's needs at any moment. (6) The Principle of Gradual Changes Transformations take place by metabolic pathways and cycles integrated by a variable number of enzymecatalyzed reactions. In each of these reactions, a gradual transformation of substrate occurs by addition or subtraction of chemical groups, linkage formation or breakdown, transformation of functional groups, and so on. As a rule, no great change takes place in the general structure of the substance or in its energetic content in a single step. Of course, the cumulative effect of all these minor changes ultimately gives rise to the major transformations that take place in metabolic pathways. Thus, the purine nucleotide biosynthesis pathway has no less than thirteen enzyme-catalyzed reactions. (7) The Principle of Interrelationship Living organisms are complex systems in which each structural and functional component is directly or indirectly connected with the rest. There is no isolated metabolic process; all of the metabolic pathways are more or less tightly related to each other. This characteristic is a result of the requirements for substances, energy or information needed for normal functioning of metabolic processes, which must be obtained from other processes or directly from the environment. At the same time, each biochemical process B I O C H E M I C A L EDUCATION 19(4) 1991
generates products that are needed by other pathways and other organisms. The utilization of substances, energy or information coming from other processes, that establish and maintain these special links among biochemical processes, is a general regularity observed in metabolism. The Cori cycle is a good example.
(8) The Principle of Transformational Reciprocity In biochemical transformations, it usually happens that if a substance A can be converted into another substance H, the reciprocal transformation of H into A is possible (and indeed probable). Although this event may occur by direct inversion of the transformation when single reactions are involved, in the case of more complex pathways, the reciprocal transformations always take place via different routes, at least for some of the steps. There are two important consequences of this situation. First, these complex biochemical processes are not controlled by the Law of Mass Action, and second, the 'differential' steps are commonly targets for the regulatory mechanisms. The biosynthesis of glucose proceeds in large part by a reversal of a number of enzymatic reactions, but it differs from glycolysis at the two critical points in the whole sequence, that is, at either end. Only in the synthesis of very specific compounds does this rule not hold. (9) The Principle of Information Transfer Living organisms are characterized by a very high degree of structural and functional organization. Perpetuation of this order is an unavoidable requisite for life to continue. In this perpetuation, molecular information, sequential or conformational, plays the major role. Basic mechanisms dealing with information in living matter follow certain regularities; whatever the steps or mechanisms involved, molecular information flows from molecules in which sequential information predominates to molecules in which conformational information is more relevant. Thus, 'everything' that a cell can do is stored in a linear sequence of nucleotides in DNA (sequential information) but cells cannot do anything unless previous synthesis of proteins (conformational information) occurs, in which process the flux stated in the principle is taking place. Conclusions Our experience is that the introduction of these principles in teaching Biochemistry to medical students is very rewarding. Students are able to understand, provided they learn the principles, the general characteristics of biochemical processes, even if they have never seen a particular pathway before. In confronting a new metabolic process, they have to learn some particular details but they are correctly oriented from the beginning with general rules that are reinforced continuously. In this way, learning is easier and fundamental knowledge is better understood and retained. Students are also better prepared for future self-education.
184 At the same time teachers do their work in a more systematic way, because they must first explain and demonstrate the principle with a few examples. What remains is mainly to work together with students in their application in a very active interaction in such a way that the new knowledge becomes more firmly established. This teaching strategy also simplifies the planning and development of academic activities, including lectures, seminars and laboratories. In our current program, the use of these Principles of Biochemistry is complemented by other generalizations such as categories, concepts, models and guiding ideas, which together constitute a useful set of didactic tools in teaching Biochemistry.
Learning from Failures MURRAY SAFFRAN
Department of Biochemistry and Molecular Biology Medical College of Ohio Toledo, Ohio 43699, USA Introduction This journal and other educational journals contain many papers that describe innovative teaching successes. The innovative programmes are evaluated by questionnaires and the students usually favour their experience by a statistically significant margin. Rarely are teaching failures described in the literature, yet I am sure that many attempts at innovations in education are unsuccessful. Can we learn from our failures? I was asked to teach the section on Nutrition and Digestion in the medical biochemistry course. In the past it was a topic that received only mild attention from the students, yet it is of great importance to the practising physician. Was it possible to stimulate more interest in Nutrition and Digestion on the part of our future physicians? We decided to try. Nutrition and Digestion We changed the schedule to bring together the lecture hours devoted to digestion by the departments of Biochemistry and Physiology, giving us a block of 2 weeks to devote to the topic. Then we gathered a team of experts in Nutrition and Digestion to outline the course. We have had previous successful experiences with group learning in student-run courses; 1'2 we agreed that the students should be able to teach the course themselves because the topics, although important in medicine, were relatively easy to understand. The medical class of about 140 students was divided into 20 groups. Each group was assigned an hour to present a section of the course. Each group would gather the information and relay it to the rest of the class in whatever way they deemed best. We encouraged the students to go beyond the lecture format in their presentations. BIOCHEMICAL
E D U C A T I O N 19(4) 1991
Seeing the Error of our Ways In retrospect, the course failed because of a series of mistakes on our part. Mistake number 1 was to tell the class about the course through class representatives, instead of meeting with the entire class. We had decided to use the channel of the class officers for a valid reason - - to spare the entire class the time of a meeting. However, the class felt that we should have met with all of them face-to-face because the class representatives were unable to answer questions that arose. Mistake number 2 was our failure to assess the receptivity of the class to a different format of teaching. This class was already angered by the perceived imposition of a new series of comprehensive examinations, replacing those on the original timetable. The students regarded the timetable as a sacred contract between them and the curriculum and any deviation from it was breaking the contract. When we changed the timetable, the anger generated by the change in the examinations spilled over onto us. Mistake number 3 was to overestimate the maturity of the students. In our previous experiences with studentmanaged courses the students responded enthusiastically to the welcome change from the endless series of lectures. They felt that they could do better than their professors, and in some cases, they did do better. But this class was different. They objected to being asked to teach each other. They were paying fees so that professors would teach them, not untrained fellow students, who might tell them wrong facts, or omit important details. Our reassurances that we would monitor the presentations and correct and add to the presentations fell on deaf ears. The insecurity of being taught by non-experts was contagious. Even those students who were enthusiastic at first, were swept up by the wave of resentment. The students also believed that preparation and presentation of the course would take too much time away from their studies and that they would have to neglect other concurrent courses. Mistake number 4 was to encourage the students to develop their own list of course objectives. They were accustomed to receiving a long list of objectives from the lecturers. When we suggested that each group should write their own objectives, which we would then review and edit, the students felt that they needed guidance in the first stages, and not after they had developed a first draft. Mistake number 5 was our expectation that the students would consult us frequently during the development of the presentations. Only two or three groups did so. The rest ignored our offers of help. Mistake number 6 was our failure to cope with the problem of the large number of students who refused to participate in the course. The resentment of the students who did the work was directed not at their recalcitrant classmates but toward us. Mistake number 7 was our laissez-faire policy toward attendance at the presentations. About 1/5 to 1/3 of the