Fatty Acid Oxidation

1. Fat Catabolism
Chapter 17

2. Fatty Acid Catabolism
– How fats are digested in animals
– How fats are mobilized and transported in tissues
– How fats are oxidized as a source of energy
– How “ketone bodies” are produced and used
Key topics: To Know

3. Oxidation of fatty acids is a major
energy source in many organisms
• About one-third of our energy needs comes from
dietary triacylglycerols
• About 80% of energy needs of mammalian heart and
liver are met by oxidation of fatty acids
• Many hibernating animals, such as grizzly bears, rely
almost exclusively on fats as their source of energy
• Some animals (camels) store fat as an eventual
source of water

4. Fats provide efficient fuel storage
• The advantage of fats over polysaccharides:
– Fatty acids carry more energy per carbon because they
are more reduced
– Fatty acids carry less water along because they are
nonpolar
• Glucose and glycogen are for short-term energy needs,
quick delivery
• Fats are for long-term (months) energy needs, good
storage, slow delivery

5. Fat Storage in White Adipose Tissue

6. Lipid Digestion

7. Chylomicron

8. Mobilization of Fat from Adipose Tissue

9. Guinea Pig Adipocytes

10. Entry of Glycerol into Glycolysis

11. Energetics of Glycerol as An Energy Source
Glycerol kinase - ATP
Glycerol-3-P DH + NADH
3-P-Gyld DH + NADH
3-PGA Kinase + ATP
Pyr Kinase + ATP
Total = 1 ATP + 2 NADH
Can GLYCEROL be FERMENTED? Explain

13. Major Fatty Acid Oxidation = β-Oxidation
Occurs in the Mitochondrion

14. β-Oxidation
Overall Flow

15. One Round (a) and Further Rounds (b) of β-
Oxidation
EOC Problem 4: explores
numbers of round of β-
oxidation.
EOC Problem 9:
Compartmentalization of
β-oxidation.

18. EOC Problem 3 Compares β-oxidation with the Citric Acid Cycle

19. Hibernating Animals Rely upon β-Oxidation for their
Sleep
EOC Problems 13, 26 and 28: Deals with Fat as Storage of Water
and Energy. Please keep in mind Prof Makemson spent a good
portion of his life in the Middle East…fat as storage of water!!

20. *Assumes 1 NADH = 2.5 ATP, and 1 FADH2 = 1.5 ATP from
Respiratory Electron Transport
Energetics of Oxidation of Palmitic Acid
EOC Problems 1 and 2 deals with amount of energy stored in fat
and how long it can last?

21. Oxidation of Unsaturated Fatty Acids (Remember
they are cis!)

22. Multiple points of
unsaturation can require
energy to get them
through β-Oxidation

23. β-Oxidation of Odd Numbered Fatty Acids
Results in Propionyl-SCoA

24. Peroxisomes in Animals
– mainly different in
First Step and Usually
use >20 C and branched
chain fatty acids.
Peroxisomes in Plants
are main fatty acid
oxidation (not in
mitochondria)
Plant vs Animal
β Oxidation

25. Seeds are Loaded with Fats and Oils

26. Arrangement of the β-Oxidation Enzymes

27. Eukaryotes Also have 2 Arrangements of these
Enzymes

28. ω-Oxidation in the ER of Liver Cells
ω = Omega, the
last letter in the
Greek alphabet
Minor pathway in
mammals, more important
in invertebrates

29. α-Oxidation of Branched Chain Fatty Acids Takes Place in
Peroxisomes

30. β-oxidation of Odd Numbered
Fatty Acids … last round
produces 1 Ac-SCoA and 1
Propionyl-SCoA

31. Formation of Ketone Bodies Occurs in the Liver
Isoprenes and
Steroids

32. Oxidation of Ketone Bodies by Non-hepatic Tissues

33. Requires
Glucogenic
Intermediates,
Glucose can not
be made from
Ac-SCoA
EOC Problem 16: About use of fatty acids in Diabetics.

34. Things to Know and Do Before Class
1. Review structure of fat, general concepts of digestion of
fat.
2. Role of glucagon to mobilize fat utilization.
3. Activation of fatty acids in cytoplasm for their oxidation
in the mitochondrion.
4. Know the steps of β-oxidation…and what is involved for
the complete oxidation of the fatty acids to CO2 and
water.
5. Know that unsaturated fatty acids are oxidized, but
energy output is different (which way?).
6. Know that other forms of fatty acid oxidation exist.
7. Know how ketone bodies are made and used.
8. EOC Problems: 1-4, 9, 10, 13, 16, 26, 28.

35. Ketone Bodies
Usually lipid and carb metabolism are balanced.
Acetyl CoA from FA spiral processed in Krebs cycle.
Hooks to oxaloacetate to make citrate.
Oxaloacetate forms from pyruvate
The product of glycolysis.
Conversion to oxaloacetate uses
pyruvate carboxylase enzyme.
What upsets the lipid / carbohydrate balance?

36. What upsets the lipid / carbohydrate balance?
1. Diet: High fat / Low carbohydrates
2. Diabetes: body cannot process glucose properly
3. Long-term fasting: starvation, crash diets,
Loozen’s blackberry eradication program, etc.
• Inadequate amount of oxaloacetate forms.
• Oxaloacetate already present is used in
gluconeogenesis to make glucose.
• Acetyl CoA cannot be processed in Krebs cycle!
• Excess Acetyl CoA makes ketone bodies.

38. 3 Ketone Bodies:
Inadequate amount of
oxaloacetate in turn
increases release of ketone
bodies from liver for use as
fuel by other tissues.
Early stages of starvation,
when last remnants of fat are
oxidized, heart & skeletal
muscles will consume ketone
bodies preserving glucose for
the brain.
Two 4 carbon chain acids &
a 3 carbon ketone

39. -Ketothiolase.
condensing 2 acetyl-CoA 
acetoacetyl-CoA
HMG-CoA Synthase
Condensation forms
hydroxymethylglutaryl-CoA
HMG-CoA Lyase
splits HMG-CoA 
acetoacetate +
acetyl-CoA.

40. Ketogenesis involves the production of ketone
bodies from acetyl CoA.
2 acetyl CoA + H2O  acetoacetate + 2 CoA + H+
Acetoacetate
converts into
the other two
ketone bodies

41. The pathway using acetoacetate as a fuel.
From citric acid cycle
Acetyl CoA can
now enter
citric acid cycle
Acetoacetate: Water soluble transportable acetyl CoA

42. The significance of Ketone Body formation:
Overall accumulation in urine and blood = ketosis
Elevated ketone body formation:
50 – 100x higher
>20 mg/100mL = ketonemia
>70 mg/100 mL flushes out of kidneys
and excreted into the urine = ketonuria
The sweet smell of acetone is on the breath
Two ketone bodies are acids.
Blood can become acidified = keto acidosis

43. Lipogenesis
Metabolic pathway for the
synthesis of fatty acids
from acetyl-CoA
Occurs any time that dietary nutrients exceed
what the body needs
for energy requirements

44. Fatty acids are intermediates in
the synthesis of other important compounds.
Examples include:
• Phospholipids
(in membranes)
• Eicosanoids,
including
prostaglandins
& leucotrienes