loading...
Section: Introduction Part 1Overall Progress: 25%

Chapter 1. The Runner's Experiment

Lehninger Principles of Biochemistry
false
true
true

The Runner's Experiment

By Justin Hines, Lafayette College and Marcy Osgood, University of New Mexico

Popup content goes in this box

New box content

Mikael Damkier/Shutterstock

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.

Photographee.eu/Shutterstock

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:

  1. Ketoacidosis
  2. Lactic acidosis
  3. Ammonia toxicity
  4. Mercury poisoning
  5. Acute hyperglycemia due to type II diabetes
  6. Hypoglycemia
  7. Phenylketonuria
  8. 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.

RECOMMENDED INITIAL INVESTIGATIONS

inv1
true
true

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.

inv2
true
true

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.

inv3
true
true

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:

inv4
true

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:

inv5
true

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.

inv6
true

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
inv101
true

1.

What is the most significant difference between these two fish oil samples in terms of their fatty acid compositions? Note: it may be helpful to briefly review fatty acid structure and nomenclature from Chapter 10 (pages 361-363) of Lehninger Principles of Biochemistry, 7th ed., before answering this question.

A.
B.
C.
D.
E.
F.

5
Correct.
Incorrect.
true
inv102
true
inv103
true
inv104
true

SECONDARY INVESTIGATIONS

true

Determine Blood Serum Concentrations

inv7
true

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)

inv105
true

5.

A defect in the urea cycle would obviously cause an increase in blood ammonia concentrations. Which of the following might also cause the concentration of ammonium ions found in the blood to increase?

A.
B.
C.
D.
E.
F.

5
Correct.
Incorrect.
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 (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: [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

6.

When a typical person runs a marathon, he or she does 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, when dietary carbohydrates are not consumed during the race, how does the body of a healthy marathon runner maintain adequate levels of blood glucose? Hint: You may wish to review pages 918-922 of Lehninger Principles of Biochemistry, 7th ed., with particular attention to the figures and to Table 23-2 before attempting the next two questions. In addition, remember to consider the sources of glucose, not ATP.

A.
B.
C.
D.
E.

4
Correct.
Incorrect.
Incorrect.
inv106b
true
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

8.

What macromolecules can be catabolized such that the resulting carbon can be used to create ketone bodies?

A.
B.
C.
D.
E.

Incorrect.
4
Correct.
Incorrect.
true
inv108
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

Determine Urine Concentrations

inv13
true

Branched-chain α-keto acids

Results for both Dave and Michael: undetectable levels (normal range: undetectable)

inv109
true

10.

What would an increased amount of branched-chain α-keto acids in the urine indicate? Hint: Be sure to review Section 18.3 (pages 690-705) of Lehninger Principles of Biochemistry, 7th ed., before attempting this question!

A.
B.
C.
D.
E.
F.

5
Correct.
Incorrect.
Incorrect.
inv14
true

Phenylpyruvate (a phenylketone)

Results for both Dave and Michael: undetectable levels (normal range: undetectable)

inv110
true

11.

What would an increased amount of phenylpyruvate in the urine indicate? Hint: Be sure to review Section 18.3 (pages 690-705) of Lehninger Principles of Biochemistry, 7th ed., before attempting this question!

A.
B.
C.
D.
E.
F.

5
Correct.
Incorrect.
Incorrect.
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

Test cells for electron transport chain enzyme activities

Results for both Dave and Michael: ETC enzyme activities were normal.

Congratulations!
You've completed this activity.
Your grade of 0% has been submitted.

Congratulations on completing this Case Study!

If your instructor has assigned the graded assessment for this case study, you can find it on the homepage of your Sapling course site.