Beta and Alpha Oxidation of Fatty acids

1. OXIDATION OF
FATTY ACIDS
β oxidation & α oxidation

2. FATTY ACIDS
• Major component of lipids
• Consists of a long hydrocarbon chain with a terminal carboxylic group
• Mainly 2 types:
i. Saturated( with no double bond)
ii. Unsaturated (with one or more double bond)

3. OXIDATION OF FATTY ACIDS
Types of oxidation
i. β – oxidation
ii. α - oxidation
iii. ω – oxidation
The Oxidation of long chain fatty acids to acetyl CoA is a central energy yielding
pathway in many organisms and tissues. For instance ,complete oxidation of a
typical fatty acid, palmitic acid, yields 2380 Kcal per mole

4. β -OXIDATION OF FATTY ACIDS
• Occurs in the cytosol of prokaryotes and in the mitochondrial matrix
of eukaryotes.
• Oxidation of fatty acids at the Beta Carbon atom
• Sequential removal of a 2- C compound, acetyl CoA
• It involves three stages
a. Activation of fatty acid
b. Transport of fatty acyl CoA into mitochondria
c. Beta oxidation proper

5. ACTIVATION OF FATTY ACID
• Fatty acid is activated by forming a thioester link with CoA.
• Activated fatty acid – Fatty acyl CoA
• Catalyzed by thiokinases /acyl CoA synthetases
• 2 step process
i. Fatty acid + ATP----------------->Acyl adenylate
ii. Acyl adenylate + CoA---------->Fatty acyl CoA

6. ACTIVATION OF FATTY ACIDS

7. TRANSPORT OF FATTY ACYL CoA TO
MITOCHONDRIA
• Smaller and medium chains acyl CoA molecules readily cross inner
mitochondrial membrane by diffusion
• Longer chains require special carnitine carrier system(carnitine
shuttle system)
• Long chains are transported by conjugating them to carnitine.
• Occurs in 4 steps
i. Acyl CoA + Carnitine + Carnitine acyl transferase I------>Acyl carnitine + CoA
ii. Acyl carnitine is transferred to mitochondrial matrix
iii. Acyl carnitine + CoA + Carnitine acyl transferase II ----->Acyl CoA + Carnitine
iv. Carnitine returns to cytosol for reuse

8. TRANSPORT OF FATTY ACYL CoA TO
MITOCHONDRIA

9. β – OXIDATION PROPER
• Each cycle of β oxidation is a sequence of four reactions
a) Oxidation(Dehydrogenation) of acyl CoA
• Acyl CoA is oxidized by an acyl CoA dehydrogenase to trans-enoyl CoA
• FAD is the electron acceptor which accepts and carry electrons go electron transport chain which
result in the synthesis of 2 ATP molecules

10. β – OXIDATION PROPER
b) Hydration of trans-enoyl CoA
• A mole of water (H2O) is added to the double bond to form β – hydroxy acyl CoA
• Catalyzed by enoyl CoA hydratase/ Crotonase.

11. β – OXIDATION PROPER
c) Oxidation of β – hydroxy acyl CoA
• β – hydroxy acyl CoA is dehydrogenated to form β ketoacyl CoA.
• Catalyzed by β – hydroxy acyl CoA dehydrogenase.
• NAD+ is the electron acceptor which accepts and carry the electrons to electron transport chain
finally generating 3ATP molecules

12. β – OXIDATION PROPER
d) Thiolysis (Cleavage/ Thioclastic scission)
• Cleavage of β ketoacyl CoA by thiol (-SH) group of second mole of CoA.
• Catalyzed by thiolase/ β ketothiolase
• It yields acetyl CoA and acyl CoA (shortened by 2 carbon atoms)
• Acetyl CoA enters TCA cycle, Acyl CoA undergoes another cycle of oxidation

13. ENERGY YIELD
• Energy yield from oxidation of fatty acids can be calculated.
• For example, the degradation of palmitic acid requires 7 reaction cycles.
• 7 FADH2 produce 14 ATP molecules(2 from each)
• 7 NADH produce 21 ATP molecules ( 3 from each)
• 8 moles of acetyl CoA yields 96 ATP molecules( 12 from each)
• 2 ATP molecules are consumed in the activation of palmitate acid.
• Net gain after complete oxidation of palmitic acid is 129 ATP (131-2)

14. α - OXIDATION OF FATTY ACIDS
• Removal of α C atom from the carboxyl end
• Occurs in peroxisomes
• Phytanic acid , an oxidation product of phytol, cannot undergo β
oxidation due to the presence of methyl group at Carbon – 3.It
undergoes initial α oxidation to remove α C as CO2. and is followed by
β oxidation.

15. α OXIDATION OF PHYTANIC ACID
a) Initially , Phytanic acid is converted into phytanoyl CoA with the
help of phytanoyl CoA synthetase.

16. α OXIDATION OF PHYTANIC ACID
b. Phytanoyl CoA is converted into α hydroxy phytanoyl CoA with the
help of Phytanoyl CoA hydroxylase. It involves addition of an OH
group at the α C atom

17. α OXIDATION OF PHYTANIC ACID
c) α hydroxy phytanoyl CoA lyase removes CO2 from α hydroxy
phytanoyl CoA as formic acid forming pristanal.

18. α OXIDATION OF PHYTANIC ACID
d) Pristanal is converted into pristanic acid ( with the help of aldehyde
dehydrogenase), in which β C atom is unsubstituted, allowing β
Oxidation.

19. α OXIDATION OF PHYTANIC ACID

20. CLINICAL CONDITIONS RELATED TO
ABNORMALITIES IN OXIDATION OF FATTY ACIDS
• SIDS( Sudden Infant Death Syndrome); due to deficiency in acyl CoA
dehydrogenase
• Jamaican vomiting sickness; due to deficiency in acyl CoA
dehydrogenase
• Refsum’s disease; due to deficiency of phytanic acid α oxidase

21. THANK YOU