Question

Compare the shuttle systems for transporting fatty acids into the mitochondria and acetyl-CoA into the cytosol.

Answer 1

Transporting fatty acids into mitochondria

• The shuttle system used in transporting fatty acids into the mitochondria is the carnitine shuttle for beta oxidation.
• The shuttle system is necessary because long chain fatty acids are impermeable through the mitochondrial membrane.
• Only long chain fatty acids require carnitine shuttle to pass through mitochondria, the medium and short chain fatty acids can pass through the membrane without the shuttle.
• Carnitine is derived from diet or is biosynthesized from the amino acids : lysine and methionine.
• The mitochondria comtains two membranes: Outer mitochondrial membrane and the inner mitochondrial membrane.
• The mitochondrial matrix lies beneath the inner mitochondrial membrane.
• 

The figure is explained in the following points

1. long chain fatty acids in the cytosol is acted on by an enzyme called Acyl-CoA synthetase . It uses two cofactors : ATP and CoASH to convert the fatty acid to fatty acyl CoA
2. The fatty acyl CoA is acted on by an enzyme CPT1 (carnitine palmitoyl transferase 1) in the outer mitochondrial membrane. This releases the CoASH from the fatty acyl CoA and converts it into fatty acyl -carnitine.This fatty acyl-carnitine enters the intermembrane space.
3. The fatty acyl-carnitine passes through the inner mitochondrial membrane through a transporter named carnitine-acylcarnitine translocase[CACT].
4. The fatty acyl carnitine that enters the mitochondrial matrix is acted on by an enzyme called CPT 2(carnitine palmitoyl transferasse 2).
5. The enzyme CPT 2 releases the carnitine bound to fatty acyl. 5.1 The carnitine relased passes back to the cytosol through the carnitine-acylcarnitine translocase.
6. The enzyme CPT2 makes use of the cofactor CoASH and coverts it into fatty acyl-CoA.
7. The fatty acyl-CoA undergoes beta oxidation and forms acetyl CoA.
8. An enzyme called carnitine-acetyl transferase makes use of the carnitine and acetyl CoA produced to form Acetyl carnitine.
9. Acetyl carnitine passes through the CACT and enters the cytosol.

Transporting Acetyl CoA into cytosol

The Acetyl CoA is transported to the cytosol through the Citrate-malate shuttle system.

The citrate-malate shuttle system is explained in the following diagram

The acteyl-CoA produced as a product of beta oxidation is transported to the cytosol in the following steps

1. Acetyl CoA combines with the enzyme Oxaloacetate forming citrate and releases CoA.
2. The citrate formed passes through the citrate transporter and enters the cytosol.
3. The citrate entering the cytosol is acted on by CoA forming Acetyl CoA and releases the oxaloacetate. To release the oxaxloacetate energy is used in the form of ATP, converting it into ADP+Pi
4. The oxaloacetate in the cytosol uses NADPH +H+ to form malate, releasing NAD+.
5. Malate enters the intermembrane space of the mitochondria and passes through the malate transporter into the inner mitochondrial membrane.
6. In the inner mitochondrial membrane, Malate is converted to oxaloacetate by using NAD+.