Oxidation of saturated fatty acids

1. Subject Name: Intermediary Metabolism
Subject Code: MTI 502
Unit No:1
Unit Name: Lipid Metabolism
Dr. Arpita Gupte

2. Oxidation of saturated fatty acids
β –Oxidation of fatty acids

3.  The formation of fatty acyl CoA molecule prepares fatty acids for entry into the mitochondria.
 Carnitine helps fatty acly CoA to enter mitochondria.
 There they are degraded in the catabolic process called β oxidation. During beta oxidation, the third
(or beta) carbon of the saturated fatty acid chain of the fatty acyl CoA is oxidized to a ketone.
 Beta oxidation is a spiral pathway.
 Each round consists of four enzyme-catalyzed steps that yield one molecule of acetyl CoA and an
acyl CoA shortened by two carbons, which becomes the starting substrate for the next round.
 Seven rounds of beta oxidation degrade a C16 fatty acid to eight molecules of acetyl CoA.
 Complete oxidation of one molecule of palmitic acid to carbon dioxide and water yields 129
molecules of ATP. One round of beta oxidation yields 17 ATP.
 Beta Oxidation is regulated by availability of free CoA, by the ratios of NAD/NADH and Q2/QH.
β – Oxidation of fatty acids

4. Beta oxidation is a spiral pathway.
Each round consists of four enzyme-
catalyzed steps that yield one
molecule of acetyl CoA and an acyl
CoA shortened by two carbons, which
becomes the starting substrate for the
next round.
Seven rounds of beta oxidation
degrade a C16 fatty acid to eight
molecules of acetyl CoA.

5. Step 1.
• Acyl-CoA Dehydrogenase catalyzes
oxidation of the fatty acid of acyl-
CoA to produce a double bond
between carbon atoms 2 & 3.
• FAD is the prosthetic group that
functions as e- acceptor for Acyl-CoA
Dehydrogenase.
• The reaction is stereospecific,
yielding a trans double bond in
enoyl-CoA.
β-Oxidation Pathway:
H3C (CH2)n C C C SCoA
H
H
H
H O
1
2
3


H3C (CH2)n C C C SCoA
H
H O
O
H2O
FADH2
FAD
H
fatty acyl-CoA
trans-2
-enoyl-CoA
Acyl-CoA Dehydrogenase

6. β-Oxidation Pathway:
Step 2.
Enoyl-CoA Hydratase catalyzes
stereospecific hydration of the
trans double bond produced in the
1st step, yielding L-hydroxyacyl-
Coenzyme A.
H3C (CH2)n C C C SCoA
H
H
H
H O
1
2
3


H3C (CH2)n C C C SCoA
H
H O
H3C (CH2)n C CH2 C SCoA
OH
O
H2O
FADH2
FAD
H
O
O
H+
+ NADH
NAD+
fatty acyl-CoA
trans-2
-enoyl-CoA
3-L-hydroxyacyl-CoA
Acyl-CoA Dehydrogenase
Enoyl-CoA Hydratase

7. β-Oxidation Pathway:
H
H3C (CH2)n C CH2 C SCoA
OH
O
H2O
H
H3C (CH2)n C CH2 C SCoA
O
O
H+
+ NADH
NAD+
CH3 C SCoA
O
H3C (CH2)n C SCoA +
O
HSCoA
3-L-hydroxyacyl-CoA
-ketoacyl-CoA
fatty acyl-CoA acetyl-CoA
(2 C shorter)
Hydroxyacyl-CoA
Dehydrogenase
-Ketothiolase
Step 3.
Hydroxyacyl-CoA
Dehydrogenase catalyzes
oxidation of the hydroxyl in the 
position (C3) to a ketone.
NAD+ is the electron acceptor.

8. β-Oxidation Pathway:
Acetyl-CoA is released, leaving
the fatty acyl in thioester linkage to
the CoA -fatty acyl-CoA (2 C less).
H3C (CH2)n C CH2 C SCoA
O
O
CH3 C SCoA
O
H3C (CH2)n C SCoA +
O
HSCoA
-ketoacyl-CoA
fatty acyl-CoA acetyl-CoA
(2 C shorter)
-Ketothiolase
Step 4.
-Ketothiolase catalyzes thiolytic
cleavage. Thiol sulfur of CoA attacks
the -keto carbon

10. β-Oxidation Pathway: SUMMARY
one round of the -oxidation pathway:
fatty acyl-CoA + FAD + NAD+ + HS-CoA 
fatty acyl-CoA (2 C less) + FADH2 + NADH + H+
+ acetyl-CoA
• The b-oxidation pathway is cyclic.
• The product, 2 carbons shorter, is the input to another round of the
pathway.
• If, as is usually the case, the fatty acid contains an even number of C
atoms, in the final reaction cycle butyryl-CoA is converted to 2
molecules of acetyl-CoA.

11. β-Oxidation Pathway: SUMMARY
 FADH2 & NADH produced during fatty acid oxidation
are reoxidized by transfer of electrons to respiratory
chain.Transfer of electrons in the respiratory chain leads
to production of ATP
 Acetyl-CoA can enter Krebs cycle, yielding additional
NADH, FADH2, and ATP.
Fatty acid oxidation is a major source of cell ATP.

12. Energetics
ATP Generation from Fatty Acid Oxidation
• The balanced equation for oxidizing one palmitoyl CoA by
seven cycles of b oxidation
Palmitoyl CoA + 7 HS-CoA + 7 FAD+ + 7 NAD+ + 7 H2O
8 Acetyl CoA + 7FADH2 + 7 NADH + 7 H+
ATP generated
8 acetyl CoA 10x8=80
7 FADH2 7x1.5=10.5
7 NADH 7x2.5=17.5
108 ATP
ATP expended to activate palmitate -2
Net yield: 106 ATP
Net yield of ATP per one oxidized palmitate
Palmitate (C15H31COOH) - 7 cycles – n/2-1

13. Thank You