Case Study Section 4 – Lipid Metabolism Adapted from “Case Study: The Runner’s E
ID: 3165357 • Letter: C
Question
Case Study Section 4 – Lipid Metabolism
Adapted from “Case Study: The Runner’s Experiment” by Justin Hines (Lehninger’s Principles of Biochemistry)
The Patients:
Two identical twin brothers, Michael and Dave Gard, are admitted to the hospital after they both collapsed while running a marathon and became non-responsive. Dave regained consciousness before reaching the hospital while Michael only regained consciousness after arriving at the hospital and was still delirious. Both are experienced marathon runners and neither man appears particularly dehydrated. Once they are both stabilized blood samples were obtained for testing. The initial evaluation of the men resulted in the following comments:
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 with sunken eyes and cheek bones and protruding ribs, indicating a lack of not only body fat but also muscle tone.
No injuries or abnormalities are apparent on either man.
Neither man smokes, drinks, or uses illegal drugs. They are not on any medications. Michael’s girlfriend Jan comments that she has been concerned with Michael’s recent weight loss and that he was not feeling well prior to the race but thought he was “just coming down with something.”
They have apparently been involved in their own “experiment” over the past several weeks
“The Experiment”:
The men plan to start a new dietary supplement company selling purified fish oil but disagreed about the best fish oil to market. They thus started an experiment to settle the 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. Shockingly they were eating NOTHING else during this time. They each had been taking approximately 330 grams of fish oil per day to provide 3000 Calories per day (normal for marathon training). They each took a different product, Michael was taking oil from wild-caught salmon and Dave was taking oil from a flathead (striped) mullet. They had a bet to determine whether fish oil was an adequate caloric-replacement for athletes and whose product was better. Both oils had been highly purified and no contaminants were found in either source.
The sources had the following composition:
Striped Mullet (Dave) Salmon (Michael)
16:0 11% 16%
16:1 D7 5% 6%
18:1 D9 15% 20%
20-, 22-, or 24-C w-3 or w-6 36% 45%
15-, 17-, 19-, and 21-C 25% 4%
12- or 14-C 6% 7%
Unidentified 2% 2%
Question 1:
Given that the main difference in the fish oil supplements is the level of odd-chain fatty acids, which of the following correctly describe the differences in even-chain and odd-chain fatty acid metabolism (select all that apply)?
A. Even-chain fatty acid oxidation produces multiple acetyl-CoA molecules while odd-chain fatty
acid oxidation produces multiple propionyl-CoA molecules.
B. Odd-chain fatty acids are not able to be broken down via ?-oxidation in humans.
C. In addition to the acetyl-CoA produced by oxidation of both even-chain and odd-chain fatty
acids, odd-chain fatty acid oxidation will produce a molecule of propionyl-CoA, which will be
converted to succinyl-CoA.
D. Even-chain fatty acids are strictly ketogenic but odd-chain fatty acids are both ketogenic and
glucogenic.
E. Odd-chain fatty acids require additional enzymatic steps to be completely degraded.
Question 2:
What is an important consequence of producing succinyl-CoA at the end of odd-chain fatty acid metabolism rather than the normal product produced by ?-oxidation of even-chain fatty acids?
A. Acetyl-CoA is a citric acid cycle intermediate but succinyl-CoA is not.
B. Acetyl-CoA is glucogenic but succinyl-CoA is strictly ketogenic.
C. Succinyl-CoA is glucogenic, but acetyl-CoA is strictly ketogenic.
D. None of the above are true.
The blood work for the men is in:
Metabolites: Dave Michael Normal
Immunoglobulins slightly low severely low
[NH4+] 20 mmol/L 67 mmol/L 12 - 48 mmol/L
Free fatty acids 500 mg/dl 660 mg/dl 190 – 420 mg/dl
Triacylglycerols 190 mg/dl 230 mg/dl 40 – 150 mg/dl
Glucose 39 mg/dl 31 mg/dl 70 – 110 mg/dl
HbA1c 4.4% 3.2% 4 – 6.5%
pH 7.31 7.20 7.35 – 7.45
Ketone bodies low but detectable dangerously high
Lactate 2.0 meq/L 0.7 meq/L 0.5 – 2.2 meq/L
Pyruvate 0.05 meq/L 0.02 meq/L 0 – 0.11 meq/L
Enzyme activities:
Lactate dehydrogenase 150 U/L 150 U/L 110 – 210 U/L
Liver Asp aminotransferase normal elevated
Liver Ala aminotransferase normal elevated
Pyruvate dehydrogenase 2.5 nmol/min*mg 2.5 nmol/min*mg 2 – 2.5 nmol/min*mg
Electron transfer chain normal normal
Carnitine acyltransferase I & II elevated elevated
The doctors are concerned because a typical person running a marathon does not become severely hypoglycemic to the extent of either Dave or Michael. Some people consume carbohydrates during the race in the form of foods, gels, or sports drinks that have added sugar. But even if they do not consume dietary carbohydrates they maintain adequate blood glucose levels.
Question 3:
How does a healthy individual maintain adequate levels of blood glucose during sustained aerobic exercise?
A. Even-numbered fatty acids are catabolized and the carbon is used for gluconeogenesis in the
liver.
B. Muscles run gluconeogenesis and export glucose into the blood.
C. Ketogenic amino acids are deaminated and the carbon skeletons are used to synthesize glucose.
D. Most blood glucose will come from the breakdown of liver glycogen and the export of this
glucose from the liver to the blood.
Question 4:
During their three-week pre-marathon self-experiment, both Dave 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 (select all that apply)?
A. Pyruvate
B. Lactate
C. Glycerol
D. ?-ketoglutarate
E. Even-chain fatty acids
F. Alanine
G. Acetyl-CoA
Question 5:
Michael has extremely high levels of blood ketone bodies. What macromolecules can be catabolized such that the resulting carbon can be used to create ketone bodies?
A. Fatty acids
B. Amino acids
C. Glucose
D. Glycogen
E. All of the above can be used to produce acetyl-CoA, so they can all be used to make ketone
bodies.
Question 6:
Why might both men have elevated carnitine acyltransferase I and II activities?
A. Levels of these enzymes rise after eating a carbohydrate rich meal to aid in carbohydrate
metabolism (glycolysis).
B. Carnitine levels rise after eating and these enzymes are expressed to catabolize the extra
carnitine.
C. Both men are producing abnormally high levels of the enzymes as a side effect of utilizing amino
acids for energy.
D. These enzymes are elevated because both men are getting their energy primarily from ?-
oxidation and these enzymes are needed for fatty acids to be transported into the mitochondria.
E. Likely both men have high levels of these enzymes because they are identical twins and share a
genetic polymorphism.
Question 7:
Why are Michael’s blood ammonia levels elevated and why are high levels of ammonia dangerous?
A. Michael’s blood ammonia is high due to the rapid degradation of proteins; high levels of ammonia
lead to dangerous levels of ketone bodies in muscle.
B. Michael’s blood ammonia is high because he has been burning calories from vigorous exercise; high
levels of ammonia lead to dangerous levels of ketone bodies in muscle.
C. Michael’s blood ammonia is high due to the rate of ketone body production in his body; high levels
of ammonia are dangerous because ammonia passes easily through the blood-brain barrier and is
highly toxic to the brain.
D. Michael’s blood ammonia is high because it is a byproduct of ?-oxidation of fatty acids; high levels
of ammonia lead to dangerous levels of ketone bodies.
E. Michael’s blood ammonia is high due to the rate of protein wasting (catabolism of non-essential
proteins to provide glucogenic carbon skeletons) in his body; high levels of ammonia are dangerous
because ammonia passes easily through the blood-brain barrier and is highly toxic to the brain.
Question 8:
Why does Michael, but not Dave, have very low levels of the immunoglobin proteins that function in the body’s immune response?
A. Immunoglobin levels are low due to an immune response to overexertion during exercise.
B. Immunoglobin levels are low due to the catabolism of non-essential protein in order to produce
glucose.
C. Immunoglobin levels are low because the body will use immunoglobins only as a first source of
protein to produce ketone bodies in the absence of dietary carbohydrates.
D. Immunoglobin levels are low because of the rapid degradation of fat for energy metabolism.
E. Immunoglobin levels are low due to the catabolism of glycogen in the muscle in order to produce
glucose.
Question 9:
What is happening to Dave and Michael with regard to their metabolisms?
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.
B. Most of their energy is coming from fatty acid oxidation, so ammonia is being produced to free up CoA for continued ?-oxidation.
C. The bothers have compromised immune systems because of a genetic disorder that affects their metabolism.
D. Their diet high in fatty acids resulted in a large build-up of glycogen in their livers and muscles.
Question 10:
Why are the twins experiencing such different symptoms?
A. Michael probably has a genetic inborn error in metabolism that Dave does not.
B. One brother is in much better shape for the run than the other because of training.
C. Michael’s case is more severe because he relies on glycolysis (by way of lactic acid fermentation) for
energy.
D. Dave’s case is milder because the supplement he is taking contains a significant amount of odd-
chain fatty acids, some of which may be used to produce glucose, thus his body is undergoing less
protein wasting and producing lesser levels of ketones.
Explanation / Answer
1) C. In addition to the acetyl-CoA produced by oxidation of both even-chain and odd-chain fatty acids, odd-chain fatty acid oxidation will produce a molecule of propionyl-CoA, which will be converted to succinyl-CoA.
2) C. Succinyl-CoA is glucogenic, but acetyl-CoA is strictly ketogenic.
3) D. Most blood glucose will come from the breakdown of liver glycogen and the export of this glucose from the liver to the blood.
During exercise, muscle glycogen is converted back into glucose, which only the muscle fibers can use as fuel. The liver converts its glycogen back into glucose, too; however, it's released directly into the bloodstream to maintain your blood sugar (blood glucose) level.
4) Pyruvate, acetyl CoA, ?-ketoglutarate, lactate, glycerol and alanine are glucogenic molecules