OXIDATION OF FATTY ACIDS

Beta Oxidation

What are the 4 pathways for the oxidation of fatty acids?

• Beta-Oxidation (major)

• Peroxisomal Oxidation

• Alpha-Oxidation

• ω oxidation

What is β oxidation?

It is a catabolic reaction that occurs during fasting as oxidation of acyl CoA to acetyl CoA where 2 carbon atoms are serially split off from carboxyl end of fatty acids.

Why is it called β oxidation?

•It is called β-oxidation because the oxidation starts at the β carbon atom of fatty acids.

Location of β oxidation?

• Tissues – liver, muscle, renal cortex, adrenal medulla, heart, etc.

• Intracellular site – mitochondria

What are the 3 stages of β oxidation?

  1. Activation of fatty acids

  2. Transport of fatty acyl coA into mitochondria

  3.Degradation (β-oxidation reactions)

Explain The 3 stages?

1. Activation of Fatty Acid

• At the cytoplasm, fatty acids are activated to form Fatty Acyl CoA by the enzyme thiokinase (acyl CoA synthetase).

• Between the carboxyl group of the fatty acid and the thiol group of coenzyme A (CoA-SH) creates a thioester bond.

• Fatty Acid + CoASH ————————> Fatty acyl CoA.

• This process uses 2 molecules of ATP.

Explain the 3 stages?

2. Transport of fatty acyl CoA into mitochondria using Carnitine Shuttle:

• β oxidation occurs in the mitochondria and the fatty acids are present in the cystol.

• The fatty acid in the cystol will be acted on an enzyme known as THIOKINASE where it utilizes ATP and CoASH and essentially adds a CoA group to the FFA and activates it and forms fatty acyl CoA.

• In the outer membrane of the mitochondria, an enzyme CPT1 is present. This enzyme will remove the CoASH group and add a carnitine group forming acylcarnitine.

• The acyl carnitine then moves pass the inner mitochondrial membrane by the enzyme CACT (Carnitine-acylcarnitine Translocase).

• In the mitochondrial matrix, the enzyme CPT2 converts acylcarnitine to Acyl CoA and carnitine is regenerated.

3. Reactions of β oxidation?

It is a cyclical process. There are 4 reactions:

1.Oxidation

2.Hydration

3.Reoxidation

4.Thiolytic cleavage

End products of β oxidation?

• Even No. of C atoms: Acetyl CoA

• Odd No. of C atoms: Acetyl CoA and propionyl CoA

Propionyl CoA can be converted to succinyl CoA which condenses with glycine to sunthesize heamoglobin

ENERGETICS OF β oxidation of Palmitic Acid (16 C) ?

• -2 ATP used in Fatty acid Synthesis.

• Finding no. of Acetyl CoA = (16/2) = 8 Acetyl CoA produced.

• No. of cycles (n-1) = (8-1) = 7 rounds

• 1 cycle of β-oxidation produces 4 ATP. Therefore, 7 cycles produces 28 ATP.

• A total of 8 acetyl CoA are produced; each one enters

TCA cycle and gives 10 ATP. 8 X 10 ATP = 80 ATP

• Net Total = (28 + 80) - 2 = 106 ATP in total

List 5 biomedical Importance of β oxidation?

1. Carnitine Deficiency: Occurs in infants. Results in hypoglycemia, raised plasma fatty acid, muscle weakness and lipid accumulation.

2. Hepatic CPT I Deficiency: hypoglycaemia and low plasma ketone bodies.

3. Muscle CPT2 Deficiency: muscle weakness and myoglobinuria.

4. Dicarboxylic Aciduria

5. Refsum’s Disease : caused by inherited defect in α-oxidation that allows accumulation of phytanic acid.

6. Zellweger’s Syndrome: due to inherited deficiency of peroxisomes. Affects brain, liver and kidney.