Chapter 1. The Runner's Experiment

Instructor's Notes

Topic Pre-requisites: Students should have exposure to the topics of Chapters 14–18 and ideally Sections 23.2 and 23.3 of Lehninger Principles of Biochemistry, 7^th ed.

Overview

This capstone-type case is designed to help students understand the importance of gluconeogenic substrates in human metabolism and the interconnections between carbohydrate, fat, and protein metabolism in humans. Because the focus of this case is the integration of metabolic pathways, we recommend that students be exposed to the topics of Chapters 14–18 and ideally Sections 23.2 and 23.3 of the textbook (Lehninger Principles of Biochemistry, 7^th ed.) before beginning this case. These latter two sections could be assigned as preliminary reading before initiating the case if they have not been explicitly covered in the class; in that case, we recommend allowing students additional time to complete this case study.

Students may work individually or in groups to complete this case study. Students are constantly encouraged to refer to their textbook throughout the case, and internet access is permitted, although it is not necessary for the completion of the case. Students are required to iteratively acquire, analyze, and integrate data as they progress through the case and answer assessment questions found throughout the case. All assessment questions are automatically scored.

For this case, students will need to explore all investigative options to complete the case, and so, unlike some other cases in this collection, the number of investigations that students make use of will not be reported.

Learning Objectives

This case is intended for remediating or extending student capabilities in these difficult topics:

1. Real-world applications of the study of human metabolism. Students will:
   • utilize real biochemical tests to evaluate and “solve” a metabolic disorder case.
   • consider the importance of factors like personal and family history, diet, medications taken, and symptoms in solving a biochemical case.
2. Critical and interrelated pathways in human central metabolism. Students will:
   • review carbohydrate, lipid, and amino acid metabolic pathways.
   • review fatty acid metabolism and recognize the distinctions between the oxidation of even- and odd-chain fatty acids.
3. Connections between carbohydrate, fat, and protein metabolism in humans. Students should be able to:
   • outline and explain the importance of gluconeogenic substrates in human metabolism.
     • understand why the inability to convert acetyl-CoA to gluconeogenic substrates in humans leads to protein wasting.
     • explain the importance of ketone body formation and ammonia transport/disposal in human metabolism.
   • explain the important differences between the metabolic intermediates produced by the oxidation of even vs. odd-chain fatty acids.
4. Practice critical thinking skills involving data. Students will:
   • evaluate data provided by metabolite and enzyme tests.
   • integrate multiple pieces of biochemical data.

Some questions are designed to address areas of difficulty for students

• Students are often confused about the necessity to maintain glucose homeostasis, even in the presence of circulating ketone bodies… that is, the concept that glucose must always be exported from the liver under all circumstances in the fasted state is not clear to most students.
• The significance of a fundamental disconnect in human metabolism--the absence of a metabolic pathway to convert acetyl-CoA ultimately to glucose--is often underappreciated or missed entirely by some students.
• The role of protein wasting as a necessary, but unfortunate consequence of the need for gluconeogenic precursors in the absence of dietary carbohydrates or stored glycogen. It is both a critical aspect of human metabolism and a relevant real-world connection given the rise of protein-heavy diets in Western society (Atkins, etc.).
• Author note: A common error is to jump immediately into testing a “pet” hypothesis by conducting laboratory tests (metabolite assays or enzyme assays) before exploring “data gathering” options like visual inspections or interviews with the person. This is an excellent and intentionally designed opportunity to point out a common mistake about the scientific method-- that is, it begins with making careful observations, rather than by immediately testing quickly formed hypotheses.

Suggested implementation

Below we describe two options for course implementation. The hybrid Online/In-class approach is recommended. Time required for students to complete the online case will vary by group depending on their level of discussion between each investigation. The case study can be started and stopped, and so it is recommended to give students a window of 3 to 5 days in which to complete the assignment.

1. Share the case study link with your students to work online outside of class, preferably in pairs or groups of three. Assign the case study to be due before your next class meeting. Students should be instructed to bring copies of notes and answers to assessment questions to the following class period.
2. Review the online answers before the following class for difficult areas for students (see expected areas of difficulty above).
3. Lead students in a discussion in pairs, groups, or as a class (depending upon class size and instructor preference) to address unresolved difficulties (~30 minutes in-class time).
4. After using the case, we recommend that you select questions from the supplied assessment questions to use on exams or as homework assignments to reinforce the difficult concepts covered. Please see the document “Exam Questions for Case 4: Integration of Metabolism.”

1. Share the case study link with your students to work online, preferably in pairs or groups of three. Assign the case study to be due before your next class meeting.
2. Review the online answers for difficult areas for students (see expected areas of difficulty above).
3. Mention or remediate tough points during a portion of lecture.
4. After using the case, we recommend that you select questions from the supplied assessment questions to use on exams or as homework assignments to reinforce the difficult concepts covered. Please see the document “Exam Questions for Case 4: Integration of Metabolism.”

Suggestions for in-class discussions (these questions may also be used in summative assessments-- i.e., exams, scored quizzes, etc.):

• What were some of the most important facts in the initial presentation of Dave and Michael’s case and why were they important?
  • Students could be directed to brainstorm in groups or as a whole class.
• What were some of the most important facts of Dave and Michael’s case that were revealed as a result of your investigations and why were they important?
  • Students could be directed to brainstorm in groups or as a whole class.
• What are some issues associated with someone trying to do a diet that is completely based on one type of macronutrient, like fat in this case, or for example a diet entirely of protein?
  • Could be easily used as a think-pair-share exercise.
  • Alternatively, students could first answer this question in writing individually, and then those responses could be collected or discussed in groups and revised.
• What was the relevance of the brothers being identical twins with respect to this case and to biochemistry in general--i.e., what might we have been concerned about if the brothers were not twins?
• What is the significance of the two oils the brothers were eating?
• What was the significance of Michael’s neurological issues?
• Why did Michael have lower levels of immunoglobins and higher levels of ketone bodies than Dave?
• Why are high levels of ketone bodies dangerous?

You are missing vital information

You may be missing vital information needed to sufficiently explain this incident. You must complete all investigations before proceeding to the final assessment questions.

You are missing vital information

You may be missing vital information needed to sufficiently explain this incident. You must complete all investigations before proceeding to the final assessment questions.

This activity has already been completed, however feel free to review the information contained within.

I am finished gathering information for this investigation and feel I am able to fully explain the reason(s) for Dave’s and Michael’s incidents in biochemical and physiological terms, including reasons for the significant differences between the two brothers’ conditions and I can fully justify and completely explain my reasoning based on the evidence I have gathered.