Biochemistry From Dr. Dhiraj J Trivedi SDM College of Medical Sciences and Hospital, Dharwad, India

2. OXIDATION
OF
FATTY ACID
Dr. Dhiraj
Trivedi

3. • 1. Explain the steps of beta oxidation and add
a note on its energetics.
• 2. Write the steps involved in the oxidation of
plamitic acid and give energy account for this
process.
• 3. Write short note on beta oxidation.
• 4. Role of carnitine in oxidation of fatty acid.
• 5. Give diagrammatic representation of
Questions to
prepare

4. Degradation OR Oxidation
• Sequential cleavage of
• two carbon unit ACETYL CO-A
• from the fatty acid

5. Types of Oxidations
• β- Oxidation ….
• Prominent pathway for most of the
fatty acid.
• ω- Oxidation …
• Minor pathway, Oxidation takes place at
ω- C atom, i.e. methyl terminus.

6. Types of Oxidations
• α- Oxidation ….
• Basically for the branched chain fatty
acid.
• Removal of one carbon unit at a time.
• Phytanic acid have methyl group at 3C, 5C
forming branch, removed by α- oxidation
and followed by β- oxidation

7. Source of
Free fatty acids
for Oxidation
Lipolysis in
Adipose tissue
Absorption from
dietary fat
SCFA & MCFA
Degradation of
chylomicrone
And VLDL
Endogenous
synthesis
From Acetyl Co-A
Normal Plasma level
10 to 30 mg%

8. β- Oxidation of fatty acids
• Oxidation on β- carbon atom
• There by sequential removal of 2 C
Acetyl Co-A from the COOH terminal of
fatty acid
• Principal oxidative pathway for
oxidation of fatty acids

9. Tissue site for β- Oxidation
• Most of the body tissue like Liver,
Kidney, lungs, adipose tissue utilize
fatty acid
• Principal oxidative pathway for cardiac
muscle derives 80% of energy from
•Except,
Brain RBC Adrenal
medulla

10. β- Oxidation
Takes place in
mitochondrial matrix
Enzymes of β- Oxidation

11. β- Oxidation
can be studied in 3 phases
• 1] Activation of Fatty acid ….
–In cytoplasm
• 2] Transport of Fatty acid ..
– From cytoplasm to mitochondrial
matrix
• 3] β- Oxidation proper

12. • End product
– ACETYL CO – A
– Reduced equivalent NADH &
FADH2
• Fate of Acetyl Co – A
• by TCA cycle to CO2 and H2O
ETC

13. Phase -- I
Activation of Fatty Acid
Free Fatty
acid
Fatty acyl Co-A
Active FA
Fatty acyl CoA synthetase
Thiokinase
Co A . SH
Mg+2
ATP AMP
+
PPi
Takes place in Cytoplasm
On outer surface of the mitochondrial membrane
2Pi
Pyrophosphatase
H2O

14. Acyl COA
Acyl CarnitineCarnitine
CoA-SH
Acyl
Carnitine
Acyl COA
Carnitine
CoA-SH
TRANSLOCA
SE
Carnitine Acyl Transferase
CAT - II
Carnitine Acyl Transferase
CAT - I
Cytoplasmic
side
Mitochondr
ial
Matrix
ansport of fatty acyl co A to mitochondrial matr


15. Genetic deficiency in
carnitine transport or
carnitine palmitoyl transferase
• Low level of carnitine in affected
tissue
• Defect in beta oxidation pathway
• Acyl carnitine complex excreted in
urine
• Hypoglycemic coma,
hyperammonemia, muscle weakness,
cardiopathy

16. β- oxidation steps
1) FAD linked Dehydrogenase
2) Hydratase
3) NAD linked Dehydrogenase
4) Thiolytic cleavage

17. 1) FAD linked Dehydrogenase
Fatty acyl CoA
, β unsaturated fatty acyl CoA
FAD+
FADH2
Fatty acyl CoA
dehydrogenase
2ATP

18. 2) Hydratase
 β unsaturated fatty acyl CoA
H2O
Enoyl CoA hydratase
β- Hydroxy acyl CoA

19. 3) NAD linked Dehydrogenase
NAD+
β- Hydroxy acyl CoA
dehydrogenase
β- Hydroxy acyl CoA
NADH +
H+
β- Keto acyl CoA
3 ATP

20. 4) Thiolytic cleavage
CoA.SH
Thiolase
β- Keto acyl CoA
Fatty acyl CoA
Less by C2
Acetyl CoA
C2 unit
Step 1
C n-2
TCA
12 ATP

21. Fatty acyl CoA
 β unsaturated fatty acyl CoA
FAD+
FADH2
Fatty acyl CoA
dehydrogenase
H2O
Enoyl CoA
hydratase
β- Hydroxy acyl CoA
NAD+
β- Hydroxy acyl CoA
dehydrogenase
NADH +
H+
β- Keto acyl CoA
CoA.SH
Thiolase
Fatty acyl CoA
Less by C2
Acetyl CoA
C2 unit
1
2
3
4

22. Energetics of Beta
Oxidation
Gross total = 131 ATP
Utilized for activation of
FA
= -- 2 ATP
Net yield = 129 ATP

23. C C C C C C C C C C C C C C C C 16
FADH2
FADH2
FADH2
FADH2
FADH2
FADH2
FADH2
NADH
NADH
NADH
NADH
NADH
NADH
NADH
7 NADH7FADH2
C C C C C C C C C C C C C C 14
C C C C C C C C C C C C 12
C C C C C C C C C C 10
C C C C C C C C 8
C C C C C C 6
C C C C 4
TCA
TCA
TCA
TCA
TCA
TCA
TCA
TCA
1
2
3
4
5
6
7
8

24. Energetics
ATP yield by β- oxidation of C16 Fatty acid
( Palmitic acid)
7FADH2 each 2 ATP = 14 ATP
7 NADH each 3 ATP = 21 ATP
8 Acetyl CoA each 12 ATP = 96 ATP
Gross total = 131 ATP
Utilized for activation of FA = -- 2 ATP
Net yield = 129 ATP

25. Regulation of β- oxidation
1. Availability of free fatty acids
2. Insulin : Glucagon ratio
3. Carnitine acyl transferase I
Insulin ↓ β- oxidation
Glucagon  β- oxidation
Inhibited by malonyl Co A

26. Disorders of β - oxidation
• Sudden Infant Death Syndrome
• Jamaican Vomiting Sickness

27. SIDS
Sudden Infant Death Syndrome
• Unexpected and unexplained death of virtually well
infant
• Common cause of death in 2 week to 1 year child
• More common in 3rd
or 4th
month,
• Premature, Male child
• Death during sleep and more in winter than summer
• Deficiency of medium chain fatty acyl Co-A
dehydrogenase
• In infants glucose is main source of energy
• Medium chain fatty acids are used for energy

28. Jamaican Vomitting Sickness
• Consumption of unripe ACKEE fruit
• Toxic amino acid HYPOGLYCIN A
• Leads to inhibition of β – oxidation
• Due to block of
• Acyl Co-A dehydrogenase
• Hypoglycemia, Vomitting, Coma,
Convulsion and death

29. Refsum’s Disease
• Disorder of  - Oxidation
• Deficiency of Phytanate  - Oxidase
• Phytanic acid can not be converted to Pristanic
acid
• Result in accumulation in Blood and Tissue
• Principal manifestation – Neurological

30. Zellweger’s Syndrome
Hepato- renal Syndrome
• Disorder of peroxisomal oxidation
• Absence of peroxisome in all tissue
• Fail to oxidize long chain fatty acids C26 –
38
• Accumulate in brain, liver and kidney

31. Oxidation of odd chain fatty
acids
• Same as the oxidation of even chain
fatty acid
• Only difference at last step
• Leaves Propionyl CoA as end product.
• It is converted to sccinyl CoA and then
oxidise in TCA cycle.

32. Metabolism of propionyl CoA
Propionyl CoA C3
D- methyl malonyl CoA
Succinyl CoAL- methyl malonyl CoA
Propionyl CoA
Carboxylase
BIOTIN
Recemase
Mutase / B12
TCA Cycle for
oxidation
CO2
C4