In the Classroom edited by
Teaching with Technology
James P. Birk
Blood-Chemistry Tutorials: Teaching Biological Applications of General Chemistry Material
Arizona State University Tempe, AZ 85287
Rachel E. Casiday, Dewey Holten, Richard Krathen, and Regina F. Frey* Department of Chemistry, Washington University, St. Louis, MO 63130; *
[email protected] Frequently, students enrolled in general chemistry courses are given little opportunity to explore the relevance of chemical concepts to the world around them (1). To foster this exploration, Washington University has introduced a series of application-oriented tutorials into the laboratory component of its general chemistry series. In conjunction with each experiment, the students complete a tutorial assignment that describes an interdisciplinary application of the concepts introduced in the laboratory. Students access the tutorials via the World Wide Web (http://www.chemistry.wustl.edu/EduDev/LabTutorials). The Web-based character of the tutorials allows students flexibility in scheduling their work on the tutorial assignments and provides valuable experience with the computer technology that has become an integral part of the study of chemistry. Each tutorial tells its own story and can stand on its own; however, the tutorials also build on one another, so students are reminded of pertinent concepts and examples from previous tutorials. In this paper, we describe a set of four tutorials (on Hemoglobin, Ferritin, Dialysis, and Buffers) that deal with chemical processes in the blood. This set provides an integrated biological context for a variety of chemical topics including metal complexes, spectroscopy, polarity, molecular size, diffusion, and equilibrium. Each tutorial is focused on a specific interdisciplinary application that incorporates the key chemical concepts introduced in the corresponding experiment.1 For example, in our course, the hemoglobin tutorial accompanies a general-chemistry experiment in which students use microscale techniques to synthesize inorganic compounds containing metal centers. The key chemical concepts introduced in the experiment are metal complexes (their coordination numbers and different ligand types), ligand-exchange processes, and electronic-absorption spectroscopy. The tutorial describes the oxygen transport by hemoglobin in the blood, which is dependent on heme, the metal complex in hemoglobin. The key concepts introduced in the tutorial are metal complexes (coordination numbers and ligand types), protein structure, and relationships between structure and function. Hence, the major concepts in the tutorial and the experiment complement each other. In addition, because the tutorials are self-contained, they may be used with different experiments or as part of a lecture course. Each tutorial begins with a list of the key chemical and application-oriented concepts to be explored, highlighting the concepts on which the students should focus as they study the tutorial. The body of the tutorial begins by introducing how the topic of the tutorial relates to the students’ everyday lives. The tutorial then shows how the topic depends on specific chemical concepts and emphasizes that, to understand the application in detail, students must understand the specific 1210
chemical concepts. In this way, the tutorials teach the key chemical concepts and any other necessary ideas in the context of the application. Interspersed throughout each tutorial are short-answer or calculational questions to help the students clarify their understanding of the application and the underlying chemistry as they progress through the tutorial. In our course, the solutions to these questions are graded and are worth 20% of the total score for each experiment. The next section of this paper describes the general story of the chemical processes in the blood, the contribution each tutorial makes to this story, and the major chemical concepts that are developed in this set of four tutorials. The third section outlines special features of the tutorials that allow students to make use of computer technology to enhance their understanding and appreciation of chemistry. The summary includes student evaluations of these tutorials. Chemistry in the Blood The blood-chemistry tutorials build upon one another to help students develop an understanding of the physiological and chemical processes that occur in the blood to maintain its metabolic status during everyday activities (Hemoglobin, Ferritin, and Dialysis tutorials) and to allow the body to cope with the stress of exercise (Buffer tutorial). In addition to the physiological and chemical processes, three major chemical concepts (protein structure and molecular structure, polarity, and chemical equilibrium) are developed over the course of the tutorials.
Hemoglobin (Oxygen-Transport Protein) The blood distributes oxygen and nutrients to the many different cells in the body, carries CO2 generated by the cells back to the lungs, and carries waste products (other than CO2) generated by the body’s metabolic activity from the cells to the kidneys and liver. Students are first introduced to these blood-chemistry processes in the tutorial “Hemoglobin and the Heme Group: Metal Complexes in the Blood” (first semester of General Chemistry). Here students learn about gas exchange in the blood (CO2 exchanged for O2 in the lungs, O2 exchanged for CO2 in the muscles). They learn that molecular oxygen is carried from the lungs to the cells (e.g., muscle cells) by hemoglobin in the blood; and that the CO2 and H+ produced by peripheral tissues may be carried by hemoglobin through the blood to the lungs or be dissolved directly in the blood (2, 3). Then the tutorial encourages the students to think more structurally by presenting the heme group as an iron complex that can bind or release molecular oxygen. Students learn how both hemoglobin and the heme group undergo conformational changes upon oxygenation and deoxygenation (2, 3). Last, since heme groups are embedded in hemoglobin, the tutorial
Journal of Chemical Education • Vol. 78 No. 9 September 2001 • JChemEd.chem.wisc.edu
In the Classroom
Figure 1. This figure, taken from the tutorial entitled “Hemoglobin and the Heme Group: Metal Complexes in the Blood”, depicts hemoglobin in the ribbon representation, with the heme groups shown in the ball-and-stick representation. The coordinates for this molecule were obtained from the Brookhaven Protein Data Bank. The rendering was made using Swiss PDB Viewer and POV-Ray Tracer (4, 5).
gives a view of hemoglobin and its major structural features. In this tutorial, students begin viewing three-dimensional molecular representations of proteins (see Fig. 1). As they study this figure, they learn about protein subunits: hemoglobin has four subunits, two α chains and two β chains, each of which is colored differently in the tutorial figure. They learn about the α helix, a common structural motif in proteins, which is shown by the ribbon representation in Figure 1 and in atomic detail in a subsequent figure in the tutorial. By viewing these molecular representations and studying the associated discussion, students begin to understand that (i) proteins are large molecules whose structures vary widely and (ii) the molecular structure of an individual protein determines the function of that protein.
Ferritin (Iron-Storage Protein) After students appreciate the importance of the ironcontaining heme group in oxygen transport, they explore the “Iron Use and Storage in the Body: Ferritin and Molecular Representations” tutorial. The iron needed to produce the heme groups of hemoglobin is stored in ferritin, which is found predominantly in the liver. This tutorial shows how iron is used and stored in the body and how it is released in a controlled fashion from ferritin when it is needed (e.g., to generate more heme groups) (6, 7). A significant change in the iron balance of the body can result in inadequate production of hemoglobin (iron deficiency) or in serious toxic effects (iron overload). Ferritin is the dominant safeguard against iron imbalance. This tutorial is written for first-semester-chemistry students with very little molecular-structure background (7). It builds upon the hemoglobin tutorial by expanding students’ understanding of protein structure and insight into different molecular representations. Varieties of two- and three-dimensional molecular representations provide a detailed picture of the structure of ferritin. Among the major features of ferritin are its extremely large size (80 Å diameter, comprising 24 subunits),
its hollow-shell shape (which allows iron to be stored inside), and its channels (which allow iron and other small molecules to enter and exit the protein’s center). Viewing the moleculargraphical representations and reading the accompanying explanations teach students the advantages and limitations of each type of representation and the different kinds of information that each type provides about protein structure. The tutorial also examines protein structure at the microscopic level in terms of amino acids as the fundamental building blocks of proteins. The students explore the general structure of an amino acid, the structures of several particular amino acids that are important in ferritin, and the formation of the peptide bonds between amino acids to build a large protein. The Ferritin tutorial introduces polarity, which is the second major chemical concept developed within this set of blood-chemistry tutorials. Polarity is introduced here because ferritin has both polar and nonpolar channels that allow for the passage of different molecules. Students learn to distinguish between polar and nonpolar amino acids. They discover that the polar channels are lined with amino acids whose polar side chains face the inside of the channel, whereas the nonpolar channels are lined with amino acids having corresponding nonpolar side chains.
Dialysis (Filtration of the Blood) Of course, iron and oxygen are not the only chemicals of importance in the blood. Blood contains particles of many sizes and types, including cells, proteins, dissolved ions, and organic waste products. Some of these are essential for the body, whereas others must be removed from the blood or they will accumulate and interfere with normal metabolism. Some chemicals are required in concentrations that must be tightly regulated, especially when the intake of these chemicals varies. The principal organ responsible for maintaining the chemical composition of the blood is the kidney (8). Students learn about the function of the kidney from the tutorial “Maintaining the Body’s Chemistry: Dialysis in the Kidneys” (second semester of General Chemistry). The kidney contains membranes that function as dialysis units to separate particles in the blood on the basis of size and polarity. For most substances, this separation occurs by passive diffusion and therefore is concentration dependent. For example, if the blood concentration of HCO3᎑ or H+ is too high, these ions are removed as the blood passes through the kidneys, which reduces their concentration. The Dialysis tutorial gives an in-depth structural view of protein channels embedded in the membranes of the kidneys. These proteins contain channels that allow certain ions and molecules to pass across the membrane while restricting the passage of others. The tutorial shows the importance of a protein’s shape (e.g., containing a hollow channel) and size (in this case, the size of the channel) in determining its function and thus furthers students’ understanding of protein structure. The concept of polarity is central to the Dialysis tutorial and is developed in detail. Students learn that the ability of ions and polar molecules to pass through a protein channel but not through the lipid portion of a membrane is dependent on the polarity of the inside of the channels and the nonpolarity of the lipid portion of the membrane. They build upon the introduction of polarity in the Ferritin tutorial to predict, based on electronegativity differences of the constituent atoms, whether a molecule has a dipole moment.2
JChemEd.chem.wisc.edu • Vol. 78 No. 9 September 2001 • Journal of Chemical Education
1211
In the Classroom
The Dialysis tutorial also introduces dynamic chemical equilibrium, in the context of molecular diffusion across a semipermeable membrane. A QuickTime movie shows the diffusion of particles across a membrane when all the diffusing particles are initially on the same side (i.e., the initial condition is a large concentration gradient) (9). At first, the concentration gradient decreases rapidly as particles travel from the area of high concentration to the area of low concentration. As the concentrations on the two sides of the membrane become closer to one another (i.e., the concentration gradient decreases), the rate of change in the concentration decreases until finally the concentrations are equal and no longer change. Students see that in this state, known as dynamic equilibrium, the particles still travel across the membrane as rapidly as before, but the amount of motion in the two directions is the same, so there is no net change. Thus students are introduced to the equilibrium concept using an application that is easy to observe. This helps them to visualize that, in an equilibrium state, chemical movement and (in later applications) chemical reaction do not stop, although the concentrations remain constant.
pH Buffers and Exercise (Acid–Base Buffering of the Blood) After seeing the importance of O2, CO2, and H+ concentrations in the blood (from the Hemoglobin tutorial) and discovering that the kidneys help to regulate the concentrations of certain chemical species in the blood (from the Dialysis tutorial), students now learn that chemicals dissolved in the blood also help to control the blood’s chemistry (8, 10, 11). To avoid serious health problems (e.g., acidosis), the pH of the blood must be held within a narrow range. To accomplish this, a series of acid–base buffers dissolved in the blood work in concert with the kidneys as they remove the waste products. The final blood-chemistry tutorial (“Blood, Sweat, and Buffers: pH Regulation during Exercise”) links information on buffering with the concepts described in the previous
tutorials to present a unified picture of what happens to the blood during exercise (8). Exercise increases the need for oxygen in the muscles. As the muscles use oxygen, the amount of molecular oxygen in the muscle tissue is depleted, setting up an O2-concentration gradient between the muscle cells and the blood in nearby capillaries. As seen in Figure 2, oxygen is carried to the muscles by hemoglobin in the blood. It then diffuses from the blood to the muscle cells via the concentration gradient, because the membranes separating the blood from the muscle cells are permeable to oxygen. In addition, because of the increased metabolism during exercise, CO2 and H+ are produced in the muscles, increasing their concentrations relative to those in the blood. Therefore CO2 and H+ flow from the muscles to the blood because the exercise-induced concentration gradients in these species are in the opposite direction from the O2 gradient. In the blood, hemoglobin picks up the extra H+ and CO2 at the same time as it undergoes a conformational change and releases O2 (2). This O2 diffuses to the muscle cells that need it. However, if the amounts of H+ and CO2 entering the blood exceed the capacity of hemoglobin, these species are dissolved directly in the blood and can alter the blood’s pH. The pH of the blood is maintained by a finely tuned buffering system consisting primarily of bicarbonate ion (HCO3᎑) and H+ in equilibrium with water and CO2 (eq 1). H+ + HCO3᎑
H2CO3
H2O + CO2
(1)
+
When H and CO2 are dissolved in the blood, they cause the buffer equilibrium to shift and lower the pH. If the pH becomes too low (
