CHAPTER 23

Oxidation of Fatty Acids and Ketone Bodies

 OBJECTIVES:

1. Between meals, lipolysis is activated in adipose tissue as a result of changes in hormone concentrations. Which responsible hormones are increased or decreased?

2. How are free fatty acids transported from adipose tissue to muscle or liver cells?

3. Name the major pathway used to oxidize fatty acids into acetyl CoA.

4. What are the reactants and products of the fatty acyl CoA synthetase reaction?

5. Describe the pathway for transport of fatty acyl CoA in the cytosol to fatty acyl CoA in the mitochondria. Use the terms carnitinepalmitoyltransferase I and II, carnitine, CoA, inner mitochondrial membrane, and carnitine acylcarnitine translocase, CoA in your explanation.

6. Use the criteria for understanding and describing all pathways to describe B-oxidation:

Names:
Functions:
Substrates:
Product:
Control Enzymes:
Regulation:
Compartment(s):
Tissues of interest:

7. Given a saturated, straight chain fatty acid, be able to calculate the number of molecules of Acetyl-CoA, FADH2, and NADH produced by B-oxidation. How much ATP would this be equivalent to?

8. Be able to name the three metabolites and two important cofactors in the conversion of part of an odd chain fatty acid to a TCA cycle intermediate. (Skip the epimerase) reaction.)

9. What are the major factors that control the synthesis of acetyl-CoA by B-oxidation muscle and/or liver?

10. Describe the pathway for the synthesis of ketone bodies by naming substrates, the first ketone body made in the pathway, the next two ketone bodies made in the pathway, the intermediate in the pathway that can be used either for ketone body synthesis or cholesterol synthesis, and the enzyme that actually produces the first ketone body as a product. Control? Where does this pathway reside?

11. Name a few tissues that oxidize ketone bodies. Why not the liver? What happens to blood ketone bodies? Name the intermediates in the pathway from B-Hydroxybutyrate to acetyl CoA. What does the enzyme succinyl CoA:acetoacetate CoA transferase do?

12. What is the effect of insulin, glucagon, or epinephrine upon lipolysis in adipose tissue?

13. What happens to the blood levels of fatty acids, glucose, and ketone bodies during an extended fast? Explain how the use of ketone bodies by the brain spares muscle protein.

14. If a person eats a balanced meal, does not exercise, and then begins a 10 hour fast. What happens to the rate of carbohydrate and fatty acid oxidation in muscle? Assume that the person dose not exercise. What would happen if they began to exercise vigorously after 5 hours?

15. How can a decrease in the insulin/glucagon ratio explain the increased production of ketone bodies during a fast?

16. Concerning Otto shape, what hormonal changes occur during the long distance run and how do they affect the release of free fatty acids from adipose tissue?

17. Concerning Otto shape, during his long distance run the change in the concentration of AMP ensures the increased uptake of fatty acyl CoA into his muscle mitochondria. Explain this using the terms: muscle contraction, ATP, AMP, AMP-dependent protein kinase, acetyl CoA carboxylase, malonyl CoA, inhibition, carnitine:palmitoyltransferase I, and carnitine-acylcarnitine translocase

18. Concerning Otto shape, during his long distance run the change in the concentration of AMP ensures the increased uptake of glucose into muscle tissue. How does this happen? Use the terms muscle contraction, ATP, AMP, AMP-dependent protein kinase, glucose transporters, and membrane.

19. Concerning Otto shape, during his long distance run the change in the concentration of ADP causes increased B-oxidation. Explain this using the terms muscle contraction, ADP, ATP synthase, proton gradient, electron transport chain, NADH oxidation, FAD(2H) oxidation, and B-oxidation.

20. Concerning Lofata Burne: Explain why medium chain acyl CoA (MCAD) deficiency would cause a decrease in ketone body synthesis during a fast. Also, from an energy point of view, explain why MCAD deficiency would increase the utilization of blood glucose by most tissues of the body and why gluconeogenesis in the liver is less than expected.

21. Concerning Di Abietes, who suffers from Type I diabetes, what is the cause of her disease? What effect does this have upon blood concentrations of glucagon, catecholamines, and cortisol? What effect do these hormones have upon fatty acid mobilization from adipose tissue? What effect does low insulin and high glucagon have upon fatty acyl CoA entrance into liver mitochondria? What is the effect upon B-oxidation? What effect does this have upon ketone body synthesis? What effect does this have upon blood pH?

22. Understand the meaning of each of the keywords.

KEYWORDS:

acetoacetate, , acetone, acetyl-CoA, acetyl CoA carboxylase, acyl CoA synthetase, adipose, albumin, ADP, AMP, AMP-dependent protein kinase, ATP, biotin, carnitine, acylcarnitine translocase, carnitine: palmitoyltransferase I, carnitine: palmitoyltransferase II, CoA, counter-regulatory hormones, CPT I, CPT II, electron transport chain, epinephrine, fatty acids, fatty acylcarnitine, FAD(2H), fatty acyl CoA synthetase, food, free fatty acids, glucagon, glucose, gluconeogenesis, HMG CoA, HMG CoA lyase, hormone, 3-hydroxy-3-methyl glutaryl CoA, B-hydroxybutryate, insulin, insulin/glucagon ratio, ketone bodies, ketones, liver, malonyl CoA, methylmalonyl CoA, mitochondrial matrix, NADH, B-oxidation, palmityl CoA, Pi, PPi, propionyl CoA, protein kinase B, pyrophosphatase, pyrophosphate, succinyl CoA, succinyl CoA:acetoacetate CoA transferase, stress hormones, TCA cycle, triacylglycerol, vitamin B12

ASSIGNMENTS:

Examine questions in chapter 23

Work questions 1, 2, 3, 4, and 5 at the end of Chapter 23

Understand the meaning of the key words in the context of Chapter 23

Practice Questions for Chapter 23 Objectives

Other Help

Third Edition Figure Map


REFERENCE: Marks' Basic Medical Biochemistry: A Clinical Approach, 2nd Edition, 2004, Williams and Wilkins (ISBN: 0-7817-2145-8) by Colleen M. Smith PhD, Allan D. Marks MD, and Michael A. Lieberman PhD

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