Question

Explain in detail how fatty acid molecules enter the matrix of mitochondria of hepatocyte cells and what happens to them in the mitochondrial matrix.

can u tell me please its a 15 marks question

Answer 1

Degradation of fatty acid occurs to breakdown fatty acids into smaller metabolites, generating acetyl-CoA at the end which then enters the citric acid cycle to generate the energy required for various metabolic processes. Fatty acid degradation happens in 3 steps. These are:

1. Lipolysis and release of fatty acids from adipose tissue.

2. Activation and transport into the mitochondria.

3. Beta oxidation of fatty acids inside mitochondria.

1. Lipolysis and release of fatty acids from adipose tissue

Adipocytes store fat cells that are broken down to release fatty acids into the bloodstream.

2. Activation and transport into the mitochondria

Before the transport of fatty acids into the mitochondria, they need to be activated first. This happens with the help of enzyme, fatty acyl-CoA synthetase. This enzyme catalyzes the reaction in which fatty acid uses an ATP molecule to convert into acyl adenylate and pyrophosphate. Subsequently, HS-CoA reacts with acyl adenylate to form activated thioester bond between the fatty acyl chain and CoA.

Transport into the mitochondrial matrix

The inner mitochondrial membrane is as such, not permeable to fatty acids but a specialized carnitine carrier system can transport activated fatty acids from cytosol to mitochondria. It requires the following steps:

1. When activated acyl-CoA reaches the outer mitochondrial membrane, it gets conjugated to carnitine in the presence of enzyme carnitine acyltransferase I to form acylcarnitine.

2. Then translocase shuttles acylcarnitine inside.

3. When acylcarnitine reaches the inner mitochondrial membrane, carnitine gets released to form acyl-CoA in the presence of enzyme carnitine acyltransferase II.

3. Beta oxidation of fatty acids inside mitochondria

Once inside the mitochondrial matrix, acyl-CoA undergoes oxidation and release energy through the following steps:

1. Fatty acids undergo beta-oxidation to form 2-C acetyl-CoA subunits.

2. 2-C acetyl-CoA subunits enter the citric acid cycle to form NADH and FADH2.

3. Reduced NADH and FADH2 enter the electron transport chain happening inside the mitochondrial matrix to release ATP.

Beta-oxidation of fatty acids requires first oxidation by FAD followed by hydration, subsequently oxidation by NAD+, then thiolysis, and finally the formation of acyl-CoA and acetyl-CoA. If the fatty acid was even-numbered, acetyl-CoA will be formed and if it had an odd number of chains, propionyl-CoA will be formed which will eventually convert into succinyl CoA. Both acetyl CoA and succinyl CoA finally enter the citric acid cycle.