Chapter 1. Sudden Onset: An Introduction to Metabolism

1.1 Introduction

Sudden Onset: An
Introduction to Metabolism

By Justin Hines, Lafayette College

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Instructor's Notes

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

Topic Prerequisites: Students should have exposure to the topics of Chapter 16 of Tymoczko Biochemistry: A Short Course, 3rd edition.

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 16 of Tymoczko, Biochemistry, 3rd edition 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.

I am ready to start the investigation.

Figure 1.1

Makali slept. His mother held his hand, staring intently at his face, breaking only to wipe away tears. It was nearly midnight and quiet in the hospital. Makali’s father was in the hallway, pacing. Other than his occasional muscle spasms, and hand tremors that didn’t interfere with his day-to-day life, Makali had been a happy and healthy teenager. Now, no one understood what was happening to him . . . and that was terrifying for his parents. Moving to the United States had always been a dream for the family, but the last 24 hours had been a nightmare of vomiting and diarrhea. His mother’s thoughts turned to her parents and she shuddered. Had the curse of the Fore people been passed on to her children? Given the family’s tragic history, she feared the worst and sobbed . . .

Introduction part 2

You are a biochemist who is working with a group of physicians. It is up to you to determine what is wrong with Makali by systematically investigating this case. Are you up to the challenge?

Introduction Part 3

About this case

In addition to reviewing some interesting and important aspects of human biochemistry, this case is meant to help you understand the mechanics of the remaining case studies in this collection. You may have free access to both your textbook and the Internet while you solve these cases, but please remember that a critical aspect of these cases is that you are meant to learn and review fundamental biochemistry concepts by thinking critically about the data presented in each case and by reviewing the relevant sections in your textbook. You are NOT to “guess” the correct disease, and we have taken great care to avoid obvious answers that can be revealed by a simple search of the Web for key terms.

In these cases, you will be placed in the shoes of someone who is investigating the case and you will have many investigation options, including tests for specific metabolites and tests to examine the activity of specific enzymes. However, it will typically be far more efficient for you to focus first on more general “information gathering” options than to immediately begin guessing and testing poorly formulated hypotheses by choosing specific tests. Therefore, we strongly suggest that you begin your investigation by gathering more information about Makali and his condition. As you will see in these cases, some investigations will open up new investigative directions and options, which may lead either to critical clues or to dead ends. It is up to you explore the case and find out! Get started by making your first choice from the options shown on the following page.

Investigation Part 1

Figure 1.2

INFORMATION-GATHERING INVESTIGATIONS

Click to select any option in any order.

Conduct a blood test for common poisons or narcotics.

Results: No poisons or narcotics were found.

Conduct a fecal analysis to look for blood and intestinal parasites.

Results: No blood or intestinal parasites were found.

Determine the blood serum concentration of glucose.

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

Determine the blood serum concentration of galactose.

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

Determine the blood serum concentration of H3O+ ions (blood pH).

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

Evaluate overall physical appearance, including the presence of insect bites or other injuries.

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.

Examine hair for common toxic compounds (heavy metals and narcotics).

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

true
true

Interview Makali’s parents to ask about the “family history.”

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.

You now have the following two new investigation options available to you:

Test common immunoglobulin (IgG, IgA, IgM) levels in the blood for signs of an infection.

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

Conduct a brain biopsy.

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.

true
true

Interview one of Makali’s friends to ask about the day he first became sick.

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.

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 16.3 of Tymozcko, Biochemistry: A Short Course, 3rd 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:

Continue to assessment questions.

Question 1.1

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10
Correct.
Incorrect.
true

Question 1.2

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3
Correct.
Incorrect.
true

Question 1.3

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3
Correct.
Incorrect.
true

Question 1.4

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4
Correct.
Incorrect.
true

Question 1.5

XhaxO00/MJuineJOhU0bsCJ2DWghp16wlGDV5rnFcuoxnlkf9khYbKcb0n8UrEjaGYhzGrTNmlBZorA+SlmQyTT3jTRK3pmaRjxDWC4rfElttAVKiErG9MyUiR4hMbC8rmJdVDx6f30WVZ1HbBIPrFZvGnaNcz+xCSt40bHQ6hkdaeIo0LLIY4pgg//xnIVhyPofVbcdO5n+XuxVezYnTfsjx4hlaNAUmJtzaT23x8EpU+MBaW3LmqT97nFZKpIS6hZ4y+U8xVKtEwGzWRUw8Kk9jEvQfJevgd+W5biMhDFv6JkCN+9+hvyYw6H+do7093omhdbUkb7kkp3D1dJUHCpNnZhXfsziaQNcVvpLy3FxC3Q/OTawdFKt07sU1w4j6qb2pM5ooI+9YqwMp+3saCoe5yW1qC7C06sbHVL6w7KiGbMPnhvOlg8misCHC/PGGNXzAEQ5Fnmm/bLzwh1arwz4xAD1AFKPL168CWpJT/JExoI2vsxjcBnwFhBawT4BPumfLBvX2UpMmqDridQVEtvhqvD+dqdoMRjYhhOTSOcoIQeCW8RRDo4BXo48XWAYqwBH7t2kPIpFfqjlw9jFfSTeFiqkEA+nymbpbsOLaM3E/vVuZhMobNJWJ+I/ECLRBQpypEXYZabUS0ShjiBUhp5xBKGgloRDNgezL+1sXDPy+w98TOS4Tb8TrcxDKWvtc5osr1nBUieXoyd5HPK1TjIgkhye3S1gVoCGdeijTQk9toguh6aKpH6Q69lbtFTnSl3xL23LTxIDxa5aCIYMuijQY+aOd5Qvb3AU0fOlIpentlygP2GXqQ4yF7+ERnhe/SKO+O4+xSSHH4ohwc9plGnSmvNwT8PPq2V/jumlzkQc6f5e9g7LHSlTbUVSxZiUpIkAtf2b6isYl+bRcMF4zMlTytbzabdKp+lW/c7HnL6zPqjKpXbvFo61++NKFPRoZWKqa3ke9QCa0rYnEErx2JqTE8Op9m6pyuuWvqVihs3b3gF7pg+42sNqLjnDVD8/6WXbEzfr3ZEJrQKtz23islMFOtcaVqJA1KLcuG39LVIP5ai1OmPWm+g+fWg1rVfXunQ7vpmYY+npIDz1cH2/hCfD7nr/DpyCVOeNtfCcsxSdhb/wHtWI7pQC9RunsyJfjxVg8KpmMDnmm9jjmg4gSU2bs3i53GzVhT43Hku2JAC9sf00UpVU/cr77pVi+0CZZvek6fIOUa8wnCmGG55cyhwZBpAPCvgmyBaLjgkc+0PUF0wy5HiDnc0pWpso0VF5SxRKY/5CABBQ6+NXLPdpAyKKDVB3yWUfK61MLqush28OxUX8FlR6/2NRlsQM+MLJLtKM/kjeakePtusRjo6srKNiSrnlkJkXENE7h+WtB9sXJmRnc0sDCRG07Dobec2XtTGkQAAbcml/KMtd5Vx4tUYwN6BgE2yvwXFNsm+i9brnNixSkg6kcDZURFWQqt1IYE9aMd1iqdPiuARDwd1gbX31VAEPbLuzR0X8TiRyRMu1GadWy2a4DrjSUOYGKJyOqaNctkqTjjFreKdXOkB1oTqR5+QmeqmFmvrzDa6tbjX4mSv6jLIcSJxnd9t9PmjB9RIK7WQUgeqUt8/dyJ/qD5IGa9QF2C36AdDwfuPdpb6DhAjmBGA8q3isQP8JRV3upaPhmjtTD2Eacaaa8dI8OuqNFZwx71BYjq9t2jVcGiHaejIP8g58CiZqJtP0PiOaPBVW/9662+xDi5EwjbEnblbhtzK6JxyC1e7FNAiqs6n9WwW0YYNeI+nBMNnBkdk7ctIOVRWV6mQSkPTQHXCH8vhU7BypD2whebJzKrtfW5sUBR62zpLqF++ToSabRsP3iEQq6VXiUyVosabWTOeao07crE4OWMHANo7B0rGdYoKfNxlNMlZ0K1ZZBNbBUnxGbQaZ+kZmq1BUnBu0wDv1tTz6Qv2c9lvDI/OyDSgb22hKuNB7OwI7L2m58Hdh6rqW3Y7qPWIwoMtIDGC0a4HPxLEK3EhAjsA7Aou+fXtAs4KlPxPvGhg+I1bBu/FDPNkM2jNuwFuxQdbI1qjzbDxdVQHZp0I/YB9Nf/4TJF4G4xUUne/V//waA1JouYjJqNNCgQ6VytZkfNpz4IcLn1XTDh+vigfyMf0RgtVvhJSOmqHJi01BEZcoSSlOV6xMAC2CvORUZmXpzM8fs+LZU2nk++wQrfoeyM6G+zTSFT07ixDk4CPJ1UxP6BceRf1rT/dpiHO/WVVdPoIi2bTI4msYOPdvh8eNmX2tv4WFs/jkL+U1S2gH9JaS0H/B7A3GpTmn7/zwtQLYOIakWvOCVJRnJqcaBZFxF0kgBsD4TyThexRylgMVqEcatYMVyzOIH3ZNiz2LG9wYGlckVN9m7K98iM9U/HkOo0FKaBdGbFgvK+eqQD4p9aA7lBm4LKPq0HR1l1/Z3al28uF7p6WaP/AcUJYBF4enpTpuDX2RNyvhfTAEyKSlm+urgl0v4POZShUduh7URgNCxHl+W9ZAgQm3k59bOm/2zZ+LTAa8RU2U9n6HuSBdTkizfJCwPEov3S0+yt91QRHjEx/F4LEgPtfuXV1KaiCS4+MyZxDVqfDBOJapAEzKlTwr86MDETSCIwGz/pV+remp1ICyzetyOT3E+9Q5AbDrbM2NNDIF72KYbER5pxjmz+WY3PHdOZZsCEMegeeiPr6dMZ+AwXFCde5bR1B6esP3hYWYxnodn+J6v7e90JPTlOjKsrfo3eweMjv/4IfRII1SNNFOduZ04otPVy236WHKfdQUR1FRS7aM+yBIT0dmr5jTuLUxK0w8TzZv2Z2b9GpL+3NJoU+SJjJXU3CJBXNsaYjnt+qLgNO2Vyjm4DbFuYAIwG+ehJbe+bps5DA9O02OnWuoZOCv+tfVL+0i1AZZ7NieDrhvI8fy8HSq1YDOXRBLrBYYf2YyLUlPiBpn9lwJM4prRscpPEClrJpT4Tp+dspGGSxkEZ92XuwOh/AmpQH+r1GW0fUN5XfPyWNG2Dlf5/XyUQ+mFtMYLh46mjrZI7os8qCvJIhPzsxYWVVRs46fD89BFXBmYkFpgJUKm00cWo6ocgPMrUdVuZep9U93slZHIj2tI0hCZA6MZ8ZTb8Zh0wJd0I2CMnQ4e8u3rU4v8tJZzZ91O0XxX4Ipvjo0JOiXg8reZ07kLfDItLB/NjH47vEi1tzcgUEsfNwGNbXgTmdyNdObdGUT0x0mbawcdYHRLGZ2SJJ5zgBHG58x9D4zd5Vr0WLk4DiHNwNasz3/oTZBvNkBCOvHL/vT7NGaUJV9x3S5APB1FXDmZBjFH2XjeIk5x0DDIiwLrjEtI97n2peqCBr5g4fKpzK4OjArx8u8TmJAfkhcAx7t1HEGVOpFReRb2EC4/QlHFWQbMx5yRvyToY6LNwBruaRmIVcmu+tOErVGQic94wDNXu6nTfBe79tJ+TEfQaNckNW5flqZ/YRn6YwjDB3I2aKXUyg4uASkf/rpYFuf65EcG0+PtZWLYvcRa3zpU0Qv0SXR7Q2p0/oklQp+531fAwWNthXwvcwfLQbGRX51TNqWapYvSwRhywvbVly6xNKdkfurEg3Pw4BXBGw1EERyU2MmO4weLlEE/3C9UT6ARlLZqkhMmvfzCF+kdmS4SzHn3YbXrew1219ATscPqBAnPvCB2CLZYrdo2VuvCSpYcYgwg08TTgmAVpJfW/ShaVtuAVEeXbyYlCmoSkpaziI5vHqzhai5dtpGiMLT7hdaZxKpDU+EHep7FpXEEHeeAyQs4TZvh92W1oKc0sjuXUJlmJKf0V6exfFSomqxTySh54wpS1xMDZs51MFwOQxPA0BuQwClyPn86wVeOUyvcGUWtjAmEX7EWFwessK/l8ygsauZVYHw+tDx6xulUztZpAhAJxskiH8wDbZNn11beceMALcLs7XHeCOBQXlZ966R60laJHUJ6TvpaXbzFY8NzlzDQVgiCgGfYz4zaP8+1qxGePWe61LrUURddr1J/yu9bgcRBDdlXsM5WCxGzeUKF0wDNQ5peOcxrQDURdWpvgaG/7QTKuWwNWEYVJI43fYxDV9ajpT80f062EaNUFAnhJFqCUjOWoMb3KcnNexaeuUYdZmRNXGNfz4VYCmnVJ/tDvPztIyd+AKe3Qkz6e1j6AyQ9G8OD0yQ0a1GX7iD11B3rZ5ldOIlZUuMhZ1DOg89R+TfCOF3a5arqoRlgKT/+JCtseikoepA8T6V4k4ajE7SeK+rZ2fs9Fq63uxzNb29da1LHQiVmG6EjKIsxu14rI5AfIfpSrVgcXu0QTgZ1jeQjCrDPqNfKyfcppv4rrHPeZjJuBippSlck+m3c/etHEvxPsKu1GVZnvOH8SQVhSKW7D7B6fP0HSR1GGRS83S98oHq5WuzW/kAUC/6CzUUjQVMLUWUzT+EqN1Z9SonOwDU5CoX2TbawKWxq2eWndyvOkwdFIe8/HOQG5qzXSvrND/p2c1XaBedfUL5fGmWcwobhRtVLaHJLxEdjs5JE94mYvuw+1ywG1qLQHWB8mjW71MAwelkvA==
9
Correct.
Incorrect.
true

Question 1.6

Which of the following three scenarios poses the most serious threat to the person’s health?

1. A lactose-intolerant person drinks a solution of galactose.

2. A lactose-intolerant person with galactosemia takes a lactose intolerance test like the one described in the previous question.

3. A lactose-tolerant person with galactosemia takes a lactose intolerance test like the one described in the previous question.

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
4
Correct.
Incorrect.
true

Question 1.7

It appears that Makali may be suffering from either lactose intolerance or galactosemia, or both. His doctor notes that galactosemia is almost always diagnosed at infancy, and so he has never seen (or even heard of) an adult who is just discovering the condition. On the other hand, lactose intolerance can begin at any point during an adult’s life (whenever the expression of lactase naturally declines). As noted in the last question, it would be very dangerous for a lactose-tolerant person with undiagnosed galactosemia to take a lactose-tolerance test like the one described earlier. This is because a lactose-tolerant person will break lactose down into its component glucose and galactose monosaccharides by the action of lactase. The test therefore subjects an individual to a huge dose of dietary galactose—very dangerous for someone with galactosemia!

You will shortly have new investigation options, including the ability to test specifically the activities of various enzymes. Before attempting to answer the next question, please review the major pathways detailed in Chapter 16 of Tymozcko, Biochemistry: A Short course, 3rd ed., to determine the pathways in which you will find the following enzymes: aldolase, galactose-1-phosphate uridyltransferase, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase. Then answer the following question.

iF8TvEYUKNfJIK1Tuk6J8t0kIv3dl13os6cPGLEu6BumalFEvDKeGFpLf1YPJdQWiG9o9wh+hbANSWTLyuHYb40iKPjJyicAWGyX14c5WJd55CQfC8+YpDe/SAzXORd4VEvAN81d1JhE+gqQf/TDPw2Sg2UJjU/F1SRnYbz0gplsXy/OPbiQ6DmW28wxO8q2eSecI5j9y07G9AJXziB9l85Pm3N5/NT2RGUo3POw8ol1ZaoJrH1XmxcYCAsUEr8ilPlot/6UHYIeLmA7eTyAxWw4gWKTPQHuQVvIsSEJhmumKW1XI6cAzlgBMg/N1wqN29DWohxigYjYWd7f
3
Correct.
Incorrect. Review the enzymes of the metabolic pathways presented on pages 285 (Figure 16.1), 296, (Figure 16.9) of Chapter 16 and pages 478-479 (Table 26.2 and Figure 26.3) Tymozcko, Biochemistry: A Short Course, 3rd ed. and try again.
Incorrect.
true
1

1

You now have the following four new investigation options available to you:

Conduct a lactose intolerance test on Makali.

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

Test the activity of the enzyme aldolase.

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

Test the activity of the enzyme galactose-1-phosphate uridyltransferase (GALT).

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.”

Question 1.8

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4
Correct.
Incorrect.
true

Question 1.9

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
3
Correct.
Incorrect.
true

Question 1.10

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4
Correct.
Incorrect.
true

Question 1.11

This is the most common effect of a block in a metabolic pathway: The substrate or substrates of the blocked enzymatic step build up to high concentrations. Sometimes the specific compound is toxic to cells, whereas in other cases the compound is re-directed through another pathway. For galactosemia, the build-up of the metabolite galactose 1-phosphate correlates with pathology, but we still don’t know for sure, at the biochemical level, what causes the many organ-specific problems associated with galactose 1-phosphate accumulation. Perhaps someday someone like you can help decipher this real biochemical mystery; its solution would help profoundly with developing new ways to treat those affected by the disorder.

The textbook states: “the disruption of galactose metabolism is referred to as galactosemia”

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2
Correct.
Incorrect.
true

Question 1.12

Makali has very little GALT activity, so he has type 1 galactosemia (also known as “classic galactosemia”). Normally type 1 is the most severe form, but because Makali has some enzyme activity (as opposed to none) and because he has serendipitously avoided galactose all his life through his diet in Papua New Guinea, he has only the mildest symptoms of the disorder: muscle spasms and tremors. These symptoms are likely the result of neurological damage that occurred in infancy before he stopped drinking milk entirely. There is one other factor still to consider.

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4
Correct.
Incorrect.
true

Question 1.13

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3
Correct.
Incorrect.
true

Question 1.14

Because of his ancestry, Makali is more likely to be lactose intolerant, as are the majority of people in the world today. There are actually other ways to measure lactase activity than the oral lactose dose test we described earlier, and these tests are safer for a person with galactosemia. One of these tests reveals that Makali is, in fact, lactose intolerant as expected. As such, he poorly digests lactose. Makali’s lactose intolerance is another important factor in his well-being: It has reduced the impact of dietary lactose and thus reduced the severity of his symptoms; his lactose intolerance partially protected Makali from his galactosemia! We hope that as a result of working on this case, you will not make the common mistake of confusing galactosemia with lactose intolerance. The latter is actually the natural condition of all adult mammals on earth except a relatively small group of humans.

The best treatment for Makali’s galactosemia is to continue avoiding consumption of galactose. In addition to dairy products, Makali must avoid leeks, broccoli, carrots, Brussels sprouts, plums, and sugar beets, all foods containing significant amounts of galactose. But, as noted in Section 16.3 of your textbook, some people with severe galactosemia still suffer severe consequences even when galactose is eliminated from the diet. This is because the human body naturally produces some galactose constantly as part of the normal turnover of glycoproteins and glycolipids containing galactose. Please answer one last question to complete the case.

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7
Correct. You have completed all essential investigations and assessment questions for this case, but you may still explore any remaining investigation options. Please feel free to open any additional may still explore any remaining investigation options. Please feel free to open any remaining investigation options to see any information that you may have missed. When you are finished, click the link below to finish the case study activity. When you are finished, click the green arrow to finish the case study activity.
Incorrect. You have completed all essential investigations and assessment questions for this case, but you may still explore any remaining investigation options. Please feel free to open any additional may still explore any remaining investigation options. Please feel free to open any remaining investigation options to see any information that you may have missed. When you are finished, click the link below to finish the case study activity. When you are finished, click the green arrow to finish the case study activity.
Incorrect.
true

Test the activity of the enzyme lactate dehydrogenase (LDH).

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

Investigate medical history including current medications.

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.

1.2 Case Summary

Congratulations on completing this Case Study! The following Case Summary gives a full explanation of the murder of Dr. John Bleu.

About this case: A debriefing

We hope that you enjoyed investigating this case and learning about a common inborn error of metabolism. As you work on additional case activities in the future, you will again have access to both your textbook and the Internet, but please remember that you should not simply guess the correct answer since getting to the correct answer is not necessarily the point of these cases. Rather, you are meant to learn and review fundamental biochemistry concepts by thinking critically about the data presented in each case, and by reviewing the relevant sections in your textbook. Trying to use Web searches of key terms to guess the answer may in fact lead you astray. For example, in the current case, you immediately learned that Makali is a member of the Fore (Makali is a traditional name of this group). A quick search of the term “Fore people” may have led you to jump to the conclusion that Makali is suffering from Kuru, the disease that made the Fore known to the rest of the world. This conclusion is a red herring, not at all supported by the details given in the case. Be sure to avoid trying to find a shortcut to the solution of future cases in this manner and remember that you should evaluate all the facts of the case as they are presented.

These cases are intended as learning tools, not evaluations. Preferably, we’d like them to be enjoyable too! We hope that in working each case you will enhance your understanding of biochemistry and your integration of biochemical information. Knowing the answer in advance only hinders your own learning, and likewise you do a disservice to others if you “spoil” the case for them. It also takes all the fun out of the activity since no one likes spoilers. Once you complete a case, please keep the answers to yourself and please don’t spoil the fun and the learning opportunity for others!