Chapter 1. Sudden Onset: An Introduction to Metabolism

Instructor's Notes

Instructor Notes for the Case Study “Sudden Onset: Introduction to Metabolism”

Topic Prerequisites: Students should have exposure to the topics of Chapters 13 and 14 in Lehninger Principles of Biochemistry, 6th ed. (Lehninger POB, 6th ed.)

Overview

The case reviews various concepts of enzyme function and the pathways of carbohydrate metabolism in the context of several interesting aspects of human physiology related to lactose and galactose metabolism. As such, we have anticipated that students will have been exposed to material in the textbook through Chapter 14 of Lehninger POB, 6th ed.prior to beginning the case. 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.

In addition to reviewing some interesting and important aspects of human biochemistry, this case is meant to be a tutorial to help students understand the mechanics of the remaining case studies in this collection. In the case introduction, students are reminded that they are meant to review and learn fundamental biochemistry concepts by thinking critically about the data presented in each case, and by reviewing the relevant sections in their textbook, rather than simply trying to “guess” the correct disease. Care has been taken to avoid obvious answers that can be revealed by a simple Web search of key terms that arise in the case. In this tutorial case, a specific red herring is planted to reinforce this idea. Likewise, because these cases are intended to be learning tools, not evaluations, we point out to students that little will be gained by spoiling the answers to these and other cases, but, rather, sharing answers only does a disservice to those who would otherwise learn from, and hopefully enjoy, working on these cases as intended.

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

• use 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. Review of critical aspects of human central metabolism. Students will review

• reactions of glycolysis.
• feeder pathways for glycolysis.
• anaerobic fermentation.
• the pentose phosphate pathway.

3. Practice critical thinking skills involving data. Students will

• evaluate data provided by metabolite and enzyme tests.
• integrate multiple pieces of biochemical data.

Suggested implementation

Below we describe two options for course implementation. The Hybrid Online/In-class approach is recommended. The time required for students to complete the online case will vary by group depending on their level of discussion between conducting each investigation. The case study can be started and stopped, and so it is recommended to give students a window of 2 to 3 days to complete the assignment.

Hybrid: Online/In-class: ( recommended approach ; ~20 minutes of classtime expected)

1. Share the case study link with your students to allow them to work online outside of class in groups or alone. Assign the case study to be due before your next class meeting. Students should be instructed to bring copies of notes and/or printed answers to assessment questions to the following class period.

2. Review the online answers before the following class to spot difficult areas for students.

3. Lead students in a discussion in pairs, in groups, or as a class (depending upon class size and instructor preference) to address unresolved difficulties (~10–15 minutes in-class time).

4. We recommend using the supplied assessment questions on exams or as homework assignments to reinforce any difficult concepts. Please see document “Exam Questions for Sudden Onset: Introduction to Metabolism.”

Online only approach: (minimal in-class time required)

1. Share the case study link with your students that will allow them to work online, outside of class in groups, or alone. Assign the case study to be due before your next class meeting.

2. Review the online answers to spot difficult areas for students.

3. Mention or remediate tough points during a portion of lecture.

4. We recommend using the supplied assessment questions on exams or as homework assignments to reinforce the difficult concepts covered. Please see document “Exam Questions for Sudden Onset: Introduction to 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 of Makali’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.
• Does Makali suffer from an inborn error of metabolism? Explain your answers. How was he able to be a healthy teenager in the past?
  • This could be easily used as a think–pair–share exercise.
  • Alternatively, students could first answer this question individually in writing, and then those responses could be collected or discussed in groups and revised.
• What was the relevance of Makali’s diet in this case?
• What are the differences between monosaccharide and disaccharide metabolism? Explain how enzyme action is important for these differences.
• Compare and contrast lactose intolerance and galactosemia. What do these disorders have in common and how are they different?
  • This could be easily used as a think–pair–share exercise.
• What type of mutations could lead to galactosemia?
  • This could be easily used as a think–pair–share exercise,
• What type of mutations might result in lactose intolerance as opposed to lactase persistence?
• With the exception of dietary sources of galactose, why do humans need a specific feeder pathway for galactose metabolism?
• What are some consequences that might occur if a particular step in a metabolic pathway is blocked due to enzyme dysfunction?

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.

You are about to leave the investigation and proceed to the final assessment. Are you sure you wish you to proceed?

Figure 1.1

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Results: No poisons or narcotics were found.

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Results: No blood or intestinal parasites were found.

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Results: [Glc] = 95 mg/dL (normal range: 70–110 mg/dL)

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Results: [Gal] = 1.5 mg/dL (normal range: 0–6.0 mg/dL)

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Results: pH = 7.4 (normal range: 7.35–7.45)

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Results: The subject is a young, adult male with a slim, athletic frame but otherwise appears normal. No insect bites or other injuries are present.

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Results: Levels of common heavy metals were normal and no narcotics were found.

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Results: Makali and his parents had recently emigrated from the highlands of Papua New Guinea. His family is part of the famous Fore tribe; after living in the tribe for most of their lives, they decided to give Makali a different life in the United States. His mother starts to cry as she recalls that both her parents died in the Kuru epidemic that made the tribe famous and she is terrified that he might be coming down with Kuru. His father interjects to say that it is not possible and that he is far more concerned that Makali has some other infectious disease to which he had never previously been exposed. For example, he says, Makali had a severe allergic reaction to the tetanus/pertussis booster shot as a child and so he has been unable to be re-vaccinated as an adult (for fear that he may go into anaphylactic shock). Therefore, Makali may be susceptible to whooping cough (pertussis). This wouldn’t have been a concern 10 years ago, but vaccination rates for whooping cough are plummeting in the United States, eliminating herd immunity in some areas, and so the disease is returning. Ironically, vaccination rates in the Fore tribe are much higher than in the United States, so Makali’s parents had concerns about coming to the United States, which is falling behind in this area of basic medical care!

The doctor you are working with says that checking immunoglobulin (Ig) levels should reveal if there is a serious infection. He also points out that Kuru does not cause Ig levels to rise. If Makali does have Kuru, then it may require a brain biopsy to diagnose it for certain.

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Results: Makali became sick after eating with friends at a pizza place. He ate pepperoni and cheese pizza, and had a vanilla milkshake and an ice cream sundae (a banana split). Apparently, Makali had never tried ice cream before coming to the United States; he had a taste of it for the first time at this same restaurant about a week ago, and this was the first time he’d been back. It was also his first time eating pizza.

Makali’s friend mentioned something about his diet; you could ask his parents more about this specifically. The following is now a new investigation option:

Ask Makali’s parents more about his diet.

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Results: Makali’s parents report that he is not on any medications currently, and, as far as they know, he has never used illegal drugs. They note his occasional muscle spasms and his constant hand tremors, but they say he has suffered from these all his life, not just since becoming ill. They note that he was sick as a baby (jaundice, diarrhea, and vomiting), but he recovered quickly and has been in general good health ever since. They also note that he has always had poor eyesight since childhood, but it’s not an issue they’ve ever looked into.

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Results: All values are in normal ranges (normal ranges: [IgG] = 560–1800 mg/dL; [IgM] = 45–250 mg/dL; [IgA] = 100–400 mg/dL).

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Results: Rejected! The physicians you work with tell you that there is not enough evidence yet that Makali has Kuru to justify a highly invasive and dangerous procedure like a brain biopsy. You should continue to gather more evidence about this case and perhaps this investigation will be justified in the future.

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Results: Makali primarily ate his mother’s cooking at home, mostly rice, beans, and taro. Because of the fear that his parents might have been exposed to Kuru, which can incubate for more than 50 years without symptoms, and because Kuru can theoretically be passed from person to person in breast milk, Makali was never breast-fed. He had gotten sick as a baby and since then had neither liked nor drank goat’s milk nor has he eaten goat cheese, both abundant in Papua New Guinea. Rather he has been very fond of coconuts and bananas since he was an infant.

Makali’s illness seems to be closely related to the consumption of dairy products. Review section 14.2 of Lehninger POB, 6th ed., for information relating to the consumption of dairy products, carbohydrate metabolism, and health issues before proceeding. Then, when you are ready to answer questions about this topic, proceed by clicking the link below:

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Results: Request denied. The doctors you are working with remind you that if we have not yet ruled out galactosemia for certain, a lactose intolerance test could be very dangerous for Makali

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Results: [Aldolase] = 3.0 U/mL (normal range: 0–7.0 U/mL)

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Results: [G6PD] = 8 U/g Hb (normal range: 5–13 U/g Hb)

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Results: [LDH] = 160 U/L (normal range: 110–210 U/L)

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Results: [GALT] = 4.0 U/g Hb (normal range: 18.5–28.5 U/g Hb)

Testing for the activity of the enzyme galactose-1-phosphate uridyltransferase (GALT) in the blood is the most common and accurate test for the most common form of galactosemia, simply called “type 1 galactosemia.”