Chapter 1. The Runner's Experiment

1.1 Introduction Part 1

Tymoczko Biochemistry: A Short Course, 3^rd

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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 17-19, 24 and 27, and ideally Chapter 30 in Tymoczko Biochemistry: A Short Course, 3^rd.

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 17-19, 24 and 27, and ideally 30 of the textbook (Tymoczko Biochemistry: A Short Course, 3^rd) 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) The 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 increased protein degradation (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 glucogenic 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 3-5 days in which to complete the assignment.

Hybrid: Online/In-class: (recommended approach; ~30 minutes of class-time expected)

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 Case 4 - Integration of Metabolism”

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

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.

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 would Michael have lower levels of non-essential proteins like 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.

Figure 1.1

Race day had come. “Finally,” thought Michael. He was a marathon veteran, but this race was different. He felt terrible. “Probably a cold” he 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.

Figure 1.2

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

Figure 1.3

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 Investigations for Proceeding with the Case

RECOMMENDED INITIAL INVESTIGATIONS

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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.

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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.

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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:

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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:

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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.

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Investigate the lipid 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.(Note: shorthand notations for fatty acids are used for some. The first number before the colon is the total number of carbons; the number after the colon is the number of double bonds; the superscripted text indicates the location of the double bonds numbered from the carboxyl-group (always cis unless otherwise specified). For example: 16:1^Δ7 means that this is a 16-carbon long fatty acid with one double bond between carbons 7 and 8. Review pages 190-193 of Tymoczko Biochemistry: A Short Course, 3^rd for additional details about fatty acid nomenclature.)

The oil consumed by Dave (from the flathead (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 wild-caught 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

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Question 1.1

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Correct.

Incorrect.

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Question 1.2

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

Correct.

Try again.

Incorrect.

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true

Question 1.3

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

Correct.

Incorrect.

true

inv104

true

Question 1.4

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

Correct. You 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.

Incorrect. 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.

true

SECONDARY INVESTIGATIONS

true

Determine Blood Serum Concentrations

inv7

true

Ammonium (NH₄⁺)

Results for Dave: [NH₄⁺] = 20 mmol/L (normal range: 12–48 mmol/L)

Results for Michael: [NH₄⁺] = 67 mmol/L (normal range: 12–48 mmol/L)

inv105

true

Question 1.5

ADpsKehPkDdottFLLoB642UIkaRM9wnePs+rcNgmZM0oJzHP71KPkqN22+YnUIOAJb/yqvccBumt9hPcmfYdk7BzcNkohFXN0Ia2TL/y0GF7QjZQ+iXpuZrCQcJhPfOSTB9iFm8DxKkWlZ0WoG1iGUZSWtrGKngEbUSkVMTN0CuceWuzuCL3Vy4BFh0oEfSs8S2jmbb7QepJ3J/z3so570F5Y1yMGmEjyp/hUiPqfyXTNL7bihO8cP/LFHjMLh3Yk47x0f7O/XGQhMjjB5KRTJK52uct2jsukq9ZIz6xUww4uMoClAwij4pldjgZ1mdxOX3h49gpHl8F99Kw9GWzo1Oo1LCgaFhQ4EKLXVaJcgNLz9Q/0AtzPD8IKiQNSrp/wRgXF6SzggD5Wn7ekxMSH4OlEGww+wmMEnGCa41p7ex7lNWhxTQoj6dpKE2Ir6dc78fnd/LQEqQChDWLvjn+r+iqKXgpLYyWNDD7ZznbaYkI/MFtFvsQ02Xq42JmmwrpkWf1TR5I+PpYLOG0MZyI2T7eIy7c6ndh4Faagvbu9F9C/rZKvoD8IG6N1Mh6VYjdZjbAUO9GckPqvFiIR3oUlYX0kD1pt3MM8XFF1SYp/JCVhZGAIO5USulERlILEcAOgoTMIpeYYIq09RDIC1ZETI0jVPSsTAw/3XstOvjrnJzeeh703dPKIzSAGRH2aZ/BntyfYgcIFn6no07ctlYQpXASRx1pJG4Pdr1IN92fHywqBHMWnYHiQjZod4cmHqUqpKvmTBmITnWzRv3zLHtJNlJ6xnxh4FQdXOQFCARkwfCuWHux49GDwZypxXrbci6k5yP/zo7SEYDEkVLZKIcegItkjhrME0eSdM5HtnDNFrH5Cy8F9rABuQWzkmEENEYcuBmfo8QJRweTXtnqLg2sz6wOHyp0F/gtoPFjWosTLIgIE0k+pK72amhfczzH/VX8ca0O8DpTPMTiukdrcvJFYB0DwetwWSdWhHshCgSb2NO6pU9rKZwgpQYM8vSo31mvncUUgc8uyJJ5iAuT97rT3gCbVsX0TK67qnR7NMyLv7a4lNMZklirOxJzjaY0KyR8kA5r+J1XSTzQ7ldpuPl/0YhE83KgLynJTswbe+9RS2vMH2kxi54WScfd0cv08wyS1/00AOXaubFiLMQv9OcSBOsx357EkmDpv7v5m41MI7wz7Vss4KIr6kH5ao2FeoWKZC/l39Vpv6h6WKDz+P77Ayz/bQfE5+fhSwQLQ8p8VHtWOg/1CkvyIG/KvAm/pTt5G+rB/it4EQEBX151fsKCIhpHsGKd/C04u9XRQgibnxa0eTzqqcdeXrYtMIcTR++jMr24z8G57hzY/CnBlACHpehZpCL0Q+Yj3vymhGP7yYVcW4MBrXQWiL+YKRWacsaGpufrMnOOz+mXSbODD+K5nt4Z9Rp4z7mbxUovSsmYGI0H0XbwnaatQdexQvbCFMeX+mlEq0XmVj4FjjlrQpscO8x1WgHheIQ4FJMc9qLB6+IW5ybjkgKrK2MW0O+oX4bNq2N3MW+6a/TTKlqmqhyTeOCVgbHgry9DAMn6GQ0amavPY97BG4C0vWMs2Rl02pbmwWxayu/YfsxsQlwYyJelYGpSZh6S/XH+8fIqmJvUJVQHe9/bm2xuReg4EiVdLQSeve+c3WHgLFmLYJ2G2xsK0agS9bbuRuPRC2wUvGY9v542bn0sctLT5k/dO0Nxo+iHRsc7t0zdJkXXCdhsVHrNgbqDVcDtlaF11vLBUWzzKIYaczZdGadQdzHvuGitYB4HKHzhZ8py2rclCQF6uqu40TDs2NzJe8/WK+i2XhcbfVO6egPrKzm+GymlTjjS+OXucsqlmrqM0dMOE6U6BYBI7D7/F1OtllA8Lcbz9NyjWiSw58qw

Correct.

Try again.

Incorrect.

inv8

true

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)

inv9

true

Glucose and Glycated Hemoglobin (HbA_1c as a marker)

Results for Dave: [Glc] = 39 mg/dL (normal range: 70–110 mg/dL) Note: This value indicates severe hypoglycemia. HbA_1c = 4.4% (normal range: 4–6.5%)

Results for Michael: [Glc] = 31 mg/dL (normal range: 70–110 mg/dL) Note: This value indicates severe hypoglycemia. HbA1c = 3.2% (normal range: 4–6.5%)

inv106

true

Question 1.6

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

Correct.

Try again.

Incorrect.

inv106b

true

Question 1.7

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

Correct.

Try again.

Incorrect.

inv10

true

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.

inv11

true

Ketone Bodies (Acetoacetate and Acetone)

Results for Dave: low but detectable levels (normal range: undetectable)

Results for Michael: dangerously high levels of both found

inv107

true

Question 1.8

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try again.

Correct.

Incorrect.

true

inv108

true

Question 1.9

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

try again.

Correct.

Incorrect.

true

inv12

true

Lactate 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);

true

Specific Enzyme Tests

inv15

true

Lactate Dehydrogenase (LDH)

Results for both Dave and Michael: [LDH] = 150 U/L (normal range: 110–210 U/L)

inv16

true

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.

inv17

true

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)

inv18

true

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

Correct.

Try again.

Incorrect.

Activity results are being submitted...

1.5 Case Summary

Congratulations on completing this Case Study! The following Case Summary gives a full explanation 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 aminotransferases) 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.