Chapter 1. The Runner's Experiment
1.1 Introduction Part 1
The Runner's Experiment
By Justin Hines, Lafayette College and Marcy Osgood, University of New Mexico
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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, 6th 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 POB,6th 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:
- 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.
- 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.
- 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.
- outline and explain the importance of gluconeogenic substrates in human metabolism.
- 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.
Hybrid: Online/In-class: (recommended approach; ~30 minutes of class-time expected)
- 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.
- Review the online answers before the following class for difficult areas for students (see expected areas of difficulty above).
- 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).
- 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.”
Online only approach: (minimal in-class time required)
- 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.
- Review the online answers for difficult areas for students (see expected areas of difficulty above).
- Mention or remediate tough points during a portion of lecture.
- 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.
You are about to leave the investigation and proceed to the final assessment. Are you sure you wish you to proceed?
Race day had come. “Finally,” thought Michael. He was a marathon veteran, but this race was different. He felt terrible. “Probably a cold” he had told his girlfriend, but nothing was going to stop him today. Today was the day he would finally prove his brother Dave wrong, and he had 26.2 miles to do it.
The two young men shook hands shortly before the race started. Dave was thin, like Michael, but not “gaunt”. Michael’s girlfriend Jan had actually used that word to describe Michael a few days before. His cheeks had receded recently. “Seriously, you should stop this… you look terrible!” Jan said. “It’s just pre-race training… and of course, the experiment,” he thought. “I’ll be fine!” he assured her with a wink before leaving their apartment.
"Today is the day we settle this!"
“Today is the day we settle this!” he now called to Dave as they took off down the race route, but Dave only smiled and accelerated to leave Michael behind. As Dave disappeared into the crowd, Michael called out, “It’s not about speed! It’s about endurance dummy!”, but Dave was too far ahead to hear.
For weeks they had been talking about their plan, the experiment, and how much money they were going to make. Michael smiled to himself and then put his head down to focus on the run. Dave was long gone but Michael was certain that he would see him again soon enough… that is, until he started to feel dizzy…
Juan had worked at several marathon medical tents before. It was always the same: people try to run the race without training properly, and they end up at the tents. Most are dehydrated and exhausted, others just “hit the wall,” when their bodies run out of glycogen, and some even have heart attacks, mainly due to poor training. This particular day wasn’t very hot, but it didn’t take much to overwhelm people during a marathon. Working the races was a nice excuse for an ER doctor to get out in the sun for a few hours on the weekend and a chance to help some people… for Juan that was as addicting as running.
Two hours in and Juan was bored. The chatter on the radio was the same as always: dehydrated runners at both tents, and one elderly person from the crowd had to be treated for heat exhaustion, though it was really just from standing too long… so far it was a slow day.
1.2 Introduction Part 2
Suddenly the radio chatter picked up. The ambulance from the medical tent at the 10-mile mark was headed in to his location at the finish line with a young man who was non-responsive. The incoming call was interrupted by a second voice: the ambulance from the medical tent at the 20-mile mark ALSO had a non-responsive man. ‘What are the odds?’ Juan thought. The two ambulances arrived simultaneously. Runner ID tags identified both subjects immediately: Michael and Dave Gard, two brothers! Dave was unconscious, but otherwise looked OK. When Juan saw Michael, however, he was startled into action; he would not have guessed that the two men were brothers!
You are a biochemistry student and you are shadowing an ER doctor who has just admitted two young males. One man, Dave, regained consciousness before arrival, whereas the other, Michael, regained consciousness only after arriving at the hospital and is still delirious. Neither man was particularly dehydrated, having drunk water during the race. Both have been stabilized, but blood and urine samples from before they were treated are available for you to test. It is up to you to discover what might be the problem with the two brothers.
Consider that there are two primary questions to answer:
- What caused both brothers to lose consciousness during the race? Here are some potential biochemical hypotheses for you to consider:
- Ketoacidosis
- Lactic acidosis
- Ammonia toxicity
- Mercury poisoning
- Acute hyperglycemia due to type II diabetes
- Hypoglycemia
- Phenylketonuria
- Maple-syrup urine disease
- What is the biochemical explanation for the differences in the conditions of the two brothers?
You may now conduct additional investigations to explore the details of this case and to test hypotheses so that you can eventually answer both questions. Note: for this case, you are encouraged to explore ALL possible investigations to gather as much information as possible to explain the case before finishing the case by continuing to the final case assessments.
1.3 Investigation Options for Proceeding with the Case
RECOMMENDED INITIAL INVESTIGATIONS
Evaluate the overall physical appearance of the two brothers, including insect bites or other injuries.
Results: The men are identical in height. Dave has a lean, athletic build, but is not unusually thin for a long-distance runner. Michael, on the other hand, appears to be severely emaciated. You note sunken eyes and cheek bones and protruding ribs, indicating a lack of not only body fat but also muscle tone. No injuries or other abnormalities are apparent.
Investigate past medical history, including current medications.
Results: Neither man smokes, drinks, or uses illegal drugs. They are not on any medications. Dave reports that Michael had not been feeling well prior to the race, but had thought that he was “just coming down with a cold or something”. Given that the men were both avid marathoners, no one apart from Michael’s girlfriend Jan had been concerned about Michael’s recent and rapid weight-loss.
Investigate the relationship between the two brothers in greater detail.
Results: Dave explains that the two men are not just brothers, they are best friends and despite their grossly different appearances at the moment, they are identical twins! He says, “Before we started our experiment just a few weeks ago, most people couldn’t tell us apart!”
Dave mentioned something about an experiment; you could ask him more about this. The following is now a new investigation option:
Ask Dave about “The Experiment”.
Results: Dave tells you that the two brothers had been planning to start a new dietary supplement company, Gard Nutraceuticals, selling purified fish oil, which they believe is a health panacea. They disagreed on the best fish oil to bring to market however, so the men had been conducting an experiment to settle this disagreement. Both had been taking fish-oil pills along with a multi-vitamin for the past three weeks while they tapered back their training runs dramatically. When you press Dave about what else he and Michael were eating, shockingly he says “nothing”. They had been eating enough fish oil to consume 3000 Calories per day, which is normal for marathon training (approximately 330 grams of fish oil per day). Each brother had been touting a different product: Michael was taking oil from wild-caught salmon, while Dave was taking oil from a flathead (striped) mullet. The bet was to determine whether fish oil was an adequate caloric-replacement supplement for athletes, and whose product was better. To make the decision unambiguous, the pair was going to use the marathon to decide the winner since the boys had nearly identical marathon times in previous races.
The details of this fish-oil experiment may merit further investigation. In particular, some fish contain high levels of mercury, which could be toxic if consumed in large quantities. You now have the following two new investigation options available to you:
Test hair for common toxins (heavy metals and narcotics) and ask Dave about mercury contamination in the supplements.
Results: Dave immediately points out that they worked with a chemist to extensively purify the fish oils to remove any mercury contamination. An independent laboratory verified that there are only trace levels of mercury left in their formulations, and Dave brings up the documentation on his smart-phone, showing that the analysis is good. Mercury toxicity will be negligible regardless of how much oil is consumed. Also, no heavy metals or narcotics were detected in hair samples from either brother.
Investigate the composition of the dietary supplements the subjects were eating.
Results: Complete hydrolysis followed by esterification of the triacylglycerols (TAGs) in the two fish oil samples allowed fatty acid composition to be analyzed by gas chromatography.
The oil consumed by Dave (from the striped mullet Mugil cephalus) contained:
- 11% 16:0
- 5% 16:1(Δ7)
- 15% 18:1(Δ9)
- 36% 20-, 22-, or 24-carbon omega-3 or omega-6
- 25% 15-, 17-, 19-, and 21-carbon fatty acids
- 6% 12- or 14-carbon fatty acids
- 2% unidentified
The oil consumed by Michael (from Atlantic salmon Salmo salar) contained:
- 16% 16:0
- 6% 16:1(Δ7)
- 20% 18:1(Δ9)
- 45% 20-, 22-, or 24-carbon omega-3 or omega-6
- 4% 15-, 17-, 19-, and 21-carbon fatty acids
- 7% 12- or 14-carbon fatty acids
- 2% unidentified
Question 1.1
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What is different about the metabolism of odd- vs. even-numbered fatty acids? (Mark “yes” for all that apply.)
| A. Odd-numbered fatty acids are not broken down by β-oxidation. | Fd/yhwSeUQ6ZqQj4 |
| B. Odd-numbered fatty acids are primarily broken down by ω-oxidation. | Fd/yhwSeUQ6ZqQj4 |
| C. Odd-numbered fatty acids cannot be broken down by humans. | Fd/yhwSeUQ6ZqQj4 |
| D. Odd-numbered fatty acids require additional enzymatic steps to fully degrade. | uS+xJY+rPntALoOB |
| E. Odd-numbered fatty acids do not require carnitine in order to be transported into the mitochondria. | Fd/yhwSeUQ6ZqQj4 |
| F. Odd-numbered fatty acid metabolism produces a 4-carbon succinyl group attached to CoA. | uS+xJY+rPntALoOB |
Question 1.3
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Question 1.4
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 have uncovered a critically important aspect of this case. As you continue exploring more investigations, consider what biochemical consequences might occur when someone is not consuming glucose and cannot convert the food that they are eating into glucose.
SECONDARY INVESTIGATIONS
Determine Blood Serum Concentrations
common immunoglobins (IgG, IgA, IgM) and ammonium (NH4+) levels
Results for Dave: All values for immunoglobin concentrations are at the low end of the normal ranges, which is normal for someone finishing a marathon. (normal ranges: [IgG] = 560–1800 mg/dL; [IgM] = 45–250 mg/dL; [IgA] = 100–400 mg/dL) [NH4+] = 20 mmol/L (normal range: 12–48 mmol/L)
Results for Michael: Severely low levels of IgG, IgM, and IgA. [NH4+] = 67 mmol/L (normal range: 12–48 mmol/L)
Question 1.5
Which of the following might cause the concentration of ammonium ions found in the blood to increase? (Mark "yes" for all that apply.)
| a. an increase in the rate of fatty acid catabolism by β-oxidation | Fd/yhwSeUQ6ZqQj4 |
| b. an increase in the rate of protein and amino acid catabolism | uS+xJY+rPntALoOB |
| c. an increase in the rate of glucose oxidation through the pentose phosphate pathway | Fd/yhwSeUQ6ZqQj4 |
| d. an increase in the rate of glucose oxidation through glycolysis and the citric acid cycle | Fd/yhwSeUQ6ZqQj4 |
| e. a defect in the urea cycle | uS+xJY+rPntALoOB |
| f. galactosemia | Fd/yhwSeUQ6ZqQj4 |
| g. lactose intolerance | Fd/yhwSeUQ6ZqQj4 |
free fatty acids (FFAs) and triacylglycerols (TAGs)
Results for Dave: 500 mg/dL FFAs (normal range: 190–420 mg/dL); 190 mg/dL TAGs (normal range: 40–150 mg/dL)
Results for Michael: 660 mg/dL FFAs (normal range: 190–420 mg/dL); 230 mg/dL TAGs (normal range: 40–150 mg/dL)
glucose and glycated hemoglobin (HbA1c as a marker)
Results for Dave: [Glc] = 39 mg/dL (normal range: 70–110 mg/dL) Note: This value indicates severe hypoglycemia. HbA1c = 4.4% (normal range: 4–6.5%)
Results for Michael: 31 mg/dL (normal range: 70–110 mg/dL) Note: This value indicates severe hypoglycemia. HbA1c = 3.2% (normal range: 4–6.5%)
Question 1.6
When a typical person runs a marathon, they do not become severely hypoglycemic to the extent that either Michael or Dave did. Some people consume carbohydrates during the race in the form of foods, gels, or sports drinks that have added sugar. However, even when dietary carbohydrates are not consumed during the race, how does the body of a healthy individual maintain adequate levels of blood glucose during sustained aerobic exercise? (Mark "yes" for all that apply.) Hint: You may wish to review pages 939–944 of Lehninger, 6th ed., with particular attention to the figures and to Table 23-2 before attempting this question!
| a. Even-numbered fatty acids are catabolized and the carbon is used for gluconeogenesis in the liver. | Fd/yhwSeUQ6ZqQj4 |
| b. Muscles run gluconeogenesis and export glucose into blood. | Fd/yhwSeUQ6ZqQj4 |
| c. Ketone bodies are produced by adipocytes and converted into glucose by the liver. | Fd/yhwSeUQ6ZqQj4 |
| d. Muscles convert lactate back into glucose and export this glucose back out into the blood. | Fd/yhwSeUQ6ZqQj4 |
| e. The exclusively ketogenic amino acids (leucine and lysine) are deaminated and the carbon skeletons used to synthesize glucose. | Fd/yhwSeUQ6ZqQj4 |
| f. Glucogenic amino acids are deaminated and the carbon skeletons used to synthesize glucose. | uS+xJY+rPntALoOB |
| g. Most blood glucose will come from the breakdown of muscle glycogen (glycogenolysis) and the export of this glucose from muscles to the blood. | Fd/yhwSeUQ6ZqQj4 |
| h. Most blood glucose will come from the breakdown of brain glycogen (glycogenolysis) and the export of this glucose from brain to the blood. | Fd/yhwSeUQ6ZqQj4 |
| i. Most blood glucose will come from the breakdown of liver glycogen (glycogenolysis) and the export of this glucose from the liver to the blood. | uS+xJY+rPntALoOB |
H3O+ ions: blood pH
Results for Dave: pH = 7.31 (normal range: 7.35–7.45)
Results for Michael: pH = 7.2 (normal range: 7.35–7.45) The physician you are shadowing tells you that a value of 7.31 indicates acidosis but that this value will not normally cause a loss of consciousness. A pH value of 7.2 indicates severe acidosis and could result in neurological problems.
ketone bodies (acetoacetate and acetone)
Results for Dave: low but detectable levels (normal range: undetectable)
Results for Michael: dangerously high levels of both found
Question 1.7
lfNPGXhSdMqbVbnX7UlMw/l7v0mNeZ3avjGYYR2NX3CJgyt/Yo0r9/MPyzYFactlhfU8K+cn3QjzkJH6e5UEZcOzfBARaOjWu6auvZyAIM6mf1V6/Xmf82T1inWs3HUBTUVCM829+xMNlgKxUTXmpdc/4PiuK7n+XmooRsjYf8Flxen7hmzanRqQy0cfRdagrJtqtxdgo9/NDbpwWOKFVWDuKJ/cfztGCjsIoUPOLlKGVQRiAGvTaRxh3tR++VeT/hNCZj8uf3ZLTcQmGNWfTBWmofzXaEiyhbNb4JzY1ynVGtC1kezTmBMPRzWpXWWorbYbsoIXOc3Qzh6atdkdzgaPuYiMvxlno872CYURNXqWGwOy11Q6d8HmHLX1SD5dYYG4xCs22lznLZ/KQuestion 1.8
77Bo2XfWfTuTPwkKm4L6JP/EPosvDkC6wD7l2i+5+k/Umdh7cRxDH/p4+N3nUx21bUA/O818Al3BYbYJwwQeuSULjKGjlBbVxu5wFqfT6JxZBg1F4HpsL2r42KBNiV0a9BEUBEFHPQghE8DLWRQ4xqxtlAtsBzKvvGqy2EzJxf7rcHKiecMUXVPgrILYdzPDEavj9OCFyFOwP2FWylGMExiJ9uxkSsf4WOGRU8zpMlYEy6+9uY9CX44lYblt5SLGNGFrMToGf3LNEhGoGgu4OVf6NuVw3wdkebg4ypIfK2YRrtJSeHCaiqjP/Nwi96gDmcCB+ub+ovmOzq/NMZ6h/qon5yX/voKaYm961ECMY5tTx+Yf9tOrxY6FshA6KsmDuEwdj4eR3LsS+knyMbq126E4Gm7ksEuhlactate and pyruvate
Results for Dave: [lactate] = 2.0 meq/L (normal range: 0.5-2.2 meq/L); [pyruvate] = 0.05 meq/L (normal range: 0–0.11 meq/L)
Results for Michael: [lactate] = 0.7 meq/L (normal range: 0.5–2.2 meq/L); [pyruvate] = 0.02 meq/L (normal range: 0–0.11 meq/L);
Determine Urine Concentrations
branched-chain α -keto acids
Results for both Dave and Michael: undetectable levels (normal range: undetectable)
Question 1.9
What would an increased amount of branched-chain a-keto acids in the urine indicate? (Mark "yes" for all that apply.)
| a. a defect in fatty acid catabolism | Fd/yhwSeUQ6ZqQj4 |
| b. a defect in fatty acid transport | Fd/yhwSeUQ6ZqQj4 |
| c. a defect in a citric acid cycle enzyme | Fd/yhwSeUQ6ZqQj4 |
| d. a defect in carbohydrate metabolism | Fd/yhwSeUQ6ZqQj4 |
| e. a defect in amino acid catabolism | uS+xJY+rPntALoOB |
| f. phenylketonuria | Fd/yhwSeUQ6ZqQj4 |
| g. lactose intolerance | Fd/yhwSeUQ6ZqQj4 |
| h. maple-syrup urine disease | uS+xJY+rPntALoOB |
phenylpyruvate (a phenylketone)
Results for both Dave and Michael: undetectable levels (normal range: undetectable)
Question 1.10
What would an increased amount of phenylpyruvate in the urine indicate? (Mark "yes" for all that apply.)
| a. a defect in fatty acid catabolism | Fd/yhwSeUQ6ZqQj4 |
| b. a defect in fatty acid transport | Fd/yhwSeUQ6ZqQj4 |
| c. a defect in a citric acid cycle enzyme | Fd/yhwSeUQ6ZqQj4 |
| d. a defect in carbohydrate metabolism | Fd/yhwSeUQ6ZqQj4 |
| e. a defect in amino acid catabolism | uS+xJY+rPntALoOB |
| f. phenylketonuria | Fd/yhwSeUQ6ZqQj4 |
| g. lactose intolerance | Fd/yhwSeUQ6ZqQj4 |
| h. maple-syrup urine disease | uS+xJY+rPntALoOB |
Specific Enzyme Tests
lactate dehydrogenase (LDH)
Results for both Dave and Michael: [LDH] = 150 U/L (normal range: 110–210 U/L)
liver Asp aminotransferase (AST) and Ala aminotransferase (ALT)
Results for Dave: Both enzymes are within the normal range (normal range: 7–55 U/L)
Results for Michael: Both enzyme levels are elevated.
pyruvate dehydrogenase (PDH)
Results for both Dave and Michael: PDH complex activity= 2.5 nmol/min*mg (normal range: 2–2.5 nmol/min*mg)
test cells for electron transport chain enzyme activities
Results for both Dave and Michael: ETC enzyme activities were normal.
1.4 Assessment
You have now completed the investigations and can go on to answer the following questions, which will give you the opportunity to demonstrate your understanding of Dave’s and Michael’s conditions.
Question 1.11
The citric acid cycle begins with the condensation of acetyl-CoA with oxaloacetate. Possible sources for carbon that may be converted into acetyl-CoA in active muscle include: (Mark "yes" for ALL that apply!)
| a. pyruvate | uS+xJY+rPntALoOB |
| b. β-oxidation of fatty acids | uS+xJY+rPntALoOB |
| c. amino acid catabolism | uS+xJY+rPntALoOB |
| d. conversion of ketone bodies from the blood back to acetyl-CoA | uS+xJY+rPntALoOB |
| e. stored glycogen in the muscle | uS+xJY+rPntALoOB |
Question 1.12
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Question 1.13
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Question 1.14
During their three-week pre-marathon self-experiment, both Dave’s and Michael’s livers had to produce some glucose. Which of the following molecules could be used by the liver to create the glucose that is needed to supply the brain and other tissues in a healthy person on a normal diet? (Mark "yes" for ALL that apply!)
| a. pyruvate | uS+xJY+rPntALoOB |
| b. lactate | uS+xJY+rPntALoOB |
| c. glycerol | uS+xJY+rPntALoOB |
| d. any citric acid cycle intermediate | uS+xJY+rPntALoOB |
| e. even-chain fatty acids | Fd/yhwSeUQ6ZqQj4 |
| f. alanine | uS+xJY+rPntALoOB |
| g. acetyl-CoA | Fd/yhwSeUQ6ZqQj4 |
Question 1.15
Select whether each the following statements about even-chain fatty acids is true or false.
| a. The product of the oxidation of even-numbered fatty acid chains is multiple acetyl groups bound to CoA molecules. | RzrZTwhMucz1zDETy1oF2g== |
| b. Humans have all the appropriate enzymes necessary to use even-chain fatty acids as gluconeogenic precursors through their conversion to acetyl-CoA. | 3PWWCFcX7vuH5EHreC3MSw== |
| c. A difference between even-chain and odd-chain fatty acids is that only odd-chain fatty acids produce propionyl groups bound to CoA. | RzrZTwhMucz1zDETy1oF2g== |
| d. The products of the oxidation of an odd-numbered fatty acid chain are multiple 3-carbon propionyl groups bound to CoA | 3PWWCFcX7vuH5EHreC3MSw== |
| e. The products of the oxidation of an odd-numbered fatty acid chain are acetyl groups and a final propionyl group attached to CoA. | RzrZTwhMucz1zDETy1oF2g== |
Question 1.16
What is happening to Dave and Michael with regard to their metabolisms? (Mark "yes" for ALL that apply!)
| a. Because the human body cannot create glucose from even-chain fatty acid oxidation, both runners are starving their bodies of glucose due to their restrictive diets. | uS+xJY+rPntALoOB |
| b. Most of their energy is coming from fatty acid oxidation, so ketone bodies are being produced to free up CoA for continued β-oxidation. | uS+xJY+rPntALoOB |
| c. The brothers have compromised immune systems because of a genetic disorder that affects their metabolism. | Fd/yhwSeUQ6ZqQj4 |
| d. Their diet high in fatty acids resulted in a large build-up of glycogen in their livers and muscles. | Fd/yhwSeUQ6ZqQj4 |
| e. Excessive fatty acid oxidation resulted in protein wasting, which led to acidification of the blood. | Fd/yhwSeUQ6ZqQj4 |
Question 1.17
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Question 1.18
LftBGzHKi6pE1SofFFXMtW1O87hnbDG09gnhc6phCJRXYBH8q4QPrx1I1Q1mLxpBeetkzPUD4xW8A2oSI99HHyj91HfxrFFhcXfuaV0KF5/Fa5c7YH/rb0/XWfbCe5EZIZLTGq15mQ46rujdjfZXgZeNZO8xrb3l9Hp3nLCOV4V9YWfUhNPIvk+3TTevV6/EZ5p4q2PD3zRI/Z8xZ7uCLsyyl4Vg/khdstH0Gedd9mRTuxj2g3iThoPxmKtCNehoy0PB2mVd2LGYK1Cpg2KyuIWVTteuKDHzMNtlLd739YMPnOZew3Bm+j285AlKa5PVA9Gcx4R7jo2P8GVRPWRV6WX72dfssOWRUixzjhMcOxRC7UDcgIT9MeVbaXSIROAxOg6r2kJpPtiVy5xMX7DbG8AWrWaY0/2USAvOl4ao0dHfSHgwKtnhDPhOAo+ZqNtQvxVK5P0eXaOwhUE6aG8P02Ic+kMgdrdFrgcrrWV4dxjDcYhltHm89gYjIGmfSFldPu/3VW3K3xi1vauQPN7a4Ag6q+ecLaEjhPGNdcRsYQj40W7rfeptUFYFVZQUXk5rJnPc/ncWbPDw4JiflvWl8/MrWoZhoZOkm/43HZ95HmJryiHzFRHrcmtQoWRzX9YYJPhxgXkah84VHE9JLYgyYz+fVn6A10ixXH22Y8+v55KfuVSBOVppsRBwuUygS6fDRWk0OEIJFwm3SfvSRrBC2xzvfMBj3qHb3O1tFdk8Xz5R+sLFvbc357xHChycR1cPwOj34gWNF2L5si2j9q9czqaw2QLriXixc1AJk4ecwsVJzqeus2M9P2UcZchmZEjoNAlcmTrKf8dKORhzpTlSmLQVm5OpEfysP23If571KyasP/akOLkTPvLk2wdSfEPam6ATIs3h1ekn9tIYz/oNPrQe1qbieDHy/Utf2bSpBKtCPaA3s3SGInrU/ApWgIYiWSHGLLi4Jfel+xBn4ij5DJAx6hNYN5DC0zBHjMuO12x63vnyAQzOna+SO7O42RFnxEJZktSiVESDDhS5lqcp3quC5M1TY8ZXLHQArZ/5/vL9t2c/rHVjarGeNxDP/1vSKFJ1b4j66pSadCV9eYbt+T1Yhs9l0f9ABeLtvYRP3bqyuX4UgBix2lJIcjo7C2QAZ/PqRzrkoSm9CiZdiMSOqqk66bnkKkpJb1TwQBV+AGgPdKGaSbY/NqPdn2KVjwVAz2B8n2JYuNHR3UhsTdbPeRvOmozGvBxoizMbRUywENLZ26AxO3CE9ntcvuZnDiLp4X2rxmtf4s/fsyHJzRCSelGZy5kGBaRwXVkYG5NpdKhrKzOHZGfWbIVRi3hMVYfLPcELYQjhXoSGgUUTHOSgIn725d8wsFJ+7XiKO6TUkdLERr95hllMjw2K2ykdaA2dXMCWeLa7HG/3GMqMs2ye25urAz8L01DjhWp5SKVKC/lLQxUCt22OZUKyam+8lx1Iq5JJ5d5GDoEOV0BYhm8jxTplVcEKavNNlIpybG5OpKBFpzt/g/OzJZESkmxeLlMSfkLrHqJSR2P6eVYKWLKUIdyw/ydU4jwNs664v6Xvke6zXB+PAbqEsWsaYx2mwH4idYXjvBpiXj/cdOzvPC7oN2TpPjq7EH/rzrwcnCuwfqju5ajfno05I/Hjyhmg9bRziKdUWGmzG4CXuGD+5ZTXjsWevn0mYH4w1vUbc7cJ2sADB+s2Ueeoy2r8LI7U1fovoHplXVdCd3MeTsUU0av6LNL1woPufa/3CgmG18XwHbzqk2cNtRLsFLYOdiqXk67tkDrtBktEncNy/r/l7xpuOXzR/Bp5FtKPhmOl2SYTjn/pKV6+VchINj0NM/2gk73YU7BQOEomh07h9cBMozZwkLHl4zwctM2CLI41PeG0Fg399hGpVfDLausVJ8DSiPYJIiMba3AJ+vldPilHD0Pox6gtAt5wPEJzrU4vFVF37m0g79N8Lgz2Y20fZKCPkS81gBV6qQ2LBi6tE4SyWVgDSY0LnEDqF/o1wv7Ciip4rv1rQenEs65gza9OhnxskHGsL3MIOxnd4Sjl9JWU2vJg3LKYPzDEGoa+tfI6Dlo/AoICw7h3f3+o/jUrzITREJkaAWSHRCUOCAcZCMP2cVKqFUcWE4GC54AuxmZ5jtqw28bw3T8CGo3FmaUcV4FOed1LqNreUj7VNs18m/mpgO6PPlkCR786PmMQ5LWi1LEXuRgxKrgtecLuRdyLg5Y5jJGKOo7BYCRQwQSyg9MbpEFJaJScmiuw23Ebb3EXN0txYojK0j4GvnYpMxud+7rki6lF/IFoHi2ViaJk9IEGPGiv1bK7EgnT/PqruCQKyy5QFJlu6yU970MZDpf11xuKXAeqpXMul6/tRvjTtGeMnGz/ju34GbDVIUhWwWAfUqY7oLgTD5iWWaAKMmcYfZq8lY56tBaSDNGAiKuQb+mO4+7YbRnErKw083ww++xUj4Fmxia0lDhAOTG+As5q85opxCHlUjyfiRckbB/sWx5VNnwzNXBPqF/gxVc/+OCpcH8h9VtM3Vr2+96PSB8xCcg=Question 1.19
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Question 1.20
What is/are the source(s) of the excessively high levels of ketone bodies in Michael but not Dave? (Mark "yes" for ALL that apply!)
| a. Ketone bodies are being formed from catabolism of carbohydrates for energy metabolism. | Fd/yhwSeUQ6ZqQj4 |
| b. Ketone bodies are being formed as a byproduct of excessive glycogenolysis. | Fd/yhwSeUQ6ZqQj4 |
| c. Ketone bodies are being formed from ketogenic amino acids released from protein catabolism. | uS+xJY+rPntALoOB |
| d. Ketone bodies are being formed from the products of β-oxidation of fatty acids from both stored triglycerols and the ingested fish oil. | uS+xJY+rPntALoOB |
| e. Ketone bodies are being produced in Michael’s brain to provide energy for the liver. | Fd/yhwSeUQ6ZqQj4 |
| f. Michael is producing large amounts of ketone bodies because he is severely hypoglycemic and has likely been hypoglycemic for most of the past few weeks. | uS+xJY+rPntALoOB |
Question 1.21
Why are the two twins experiencing such different symptoms?
| a. Michael probably has a genetic inborn error in metabolism that Dave does not. | Fd/yhwSeUQ6ZqQj4 |
| b. One brother is in much better shape for the run than the other because of training. | Fd/yhwSeUQ6ZqQj4 |
| c. Michael’s case is more severe because he relies on glycolysis (by way of lactic acid fermentation) for energy. | Fd/yhwSeUQ6ZqQj4 |
| d. Michael’s supplement has almost no odd-numbered fatty acids, so his body is undergoing more protein wasting, and producing dangerous levels of ketones. | uS+xJY+rPntALoOB |
| e. Dave’s case is milder because the supplement he is taking contains a significant amount of odd-numbered fatty acids, some of which may be used to produce glucose. | uS+xJY+rPntALoOB |
| f. The twins exhibit minor variations in metabolic adaptation to dietary changes based on their genetics. | Fd/yhwSeUQ6ZqQj4 |
Question 1.22
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Question 1.23
What is causing Michael’s neurological issues and what is the cause of this problem? (Mark "yes" for ALL that apply!)
| a. Michael is exhibiting the first signs of diabetes, triggered by the vigorous run. | Fd/yhwSeUQ6ZqQj4 |
| b. Michael has depleted his main stores of glucose and is therefore experiencing neurological effects from hypoglycemia. | Fd/yhwSeUQ6ZqQj4 |
| c. Michael has severe hypoglycemia and severe ketoacidosis. | uS+xJY+rPntALoOB |
| d. As a result of excessive protein degradation, Michael is also experiencing mild ammonia toxicity, which is likely exacerbating his neurological issues. | uS+xJY+rPntALoOB |
| e. Michael is experiencing side effects of extreme dehydration. | Fd/yhwSeUQ6ZqQj4 |
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1.5 Case Summary
Congratulations on completing this Case Study! The following Case Summary gives a full explanations of the two brothers’ conditions.
Case Summary
Because the human body cannot create glucose from the oxidation of even-chain fatty acids, both runners are starving their bodies of glucose due to their restrictive diets. Most of their energy is coming from fatty acid oxidation, so ketone bodies are being produced to free up CoA for more β-oxidation. Because their diet lacks carbohydrates and glucogenic amino acids, their glycogen levels will be very low before the race, regardless of their caloric intake. Their blood sugar is low and their bodies are compensating through protein wasting, resulting in their thin and emaciated appearances, and through ketone body production, resulting in acidified blood.
The differences between the two brothers’ conditions are not due to genetic polymorphisms (they are identical twins), but rather, arise from the composition of odd- vs. even-numbered fatty acids in their respective supplements. Even-chain fatty acids are NOT gluconeogenic precursors because the product of even-numbered fatty acid chain oxidation is multiple 2-carbon acetyl groups bound to CoA. Humans lack the enzymes necessary to use acetyl-CoA as a gluconeogenic precursor. In contrast, odd-numbered fatty acid catabolism produces one succinate (a 4-carbon citric acid cycle intermediate) for each fatty acid molecule oxidized. The result is that two glucose molecules (12 carbons total) can be produced from the oxidation of every three odd-numbered fatty acids.
Dave’s case is milder because the supplement he is taking contains a significant amount of odd-numbered fatty acids, and some of these may be used to produce glucose. Michael’s supplement has almost no odd-numbered fatty acids, so his body is undergoing more protein wasting (resulting in lower levels of non-essential body proteins like immunoglobins), and producing dangerous levels of ketones.
Ketone bodies are being formed BOTH from the products of β-oxidation of the fatty acids from the ingested fish oil and from ketogenic amino acids released from protein catabolism. Michael’s levels are higher than Dave’s because his body is undergoing protein wasting at a greater rate. Higher rates of protein wasting are the reason for Michael’s elevated levels of Asp aminotransferase (AST) and Ala aminotransferase (ALT). These enzymes (and additional aminotransfereases) are being produced in greater quantities to carry out the massive amount of amino acid deamination that must occur under these conditions. As a result of excessive protein degradation, Michael is also experiencing mild ammonia toxicity (in addition to all his other problems!). Ammonia passes readily through the blood-brain barrier and is highly toxic to the brain.