Biochimie | Métabolisme des lipides | Partie 02/06

Summary

This script delves into the biochemical process of fatty acid degradation, explaining how fatty acids must first be activated before undergoing beta-oxidation. It highlights the key steps involved, such as the activation of glucose and fatty acids, transport mechanisms through carnitine, and the sequence of reactions in beta-oxidation. The script provides a detailed breakdown of these steps, including hydrogenation, hydration, and cleavage, leading to the formation of acetyl-CoA. The final part includes an example calculation for energy yield from the oxidation of an 8-carbon saturated fatty acid, illustrating the ATP production during the process.

Takeaways

• 😀 Fatty acids must be activated before undergoing metabolism, a process that requires phosphorylation (e.g., glucose is phosphorylated to glucose-6-phosphate).
• 😀 Activation of fatty acids involves attaching CoA to form acyl-CoA, which is necessary for their breakdown.
• 😀 Fatty acids must be transported into the mitochondria for oxidation, which is facilitated by carnitine and specific enzymes (carnitine acyltransferase I and II).
• 😀 Acyl-CoA can pass through mitochondrial membranes with the help of carnitine acyltransferase enzymes.
• 😀 Once inside the mitochondria, fatty acids undergo beta-oxidation, a series of four reactions that break down the fatty acid chain into two-carbon acetyl-CoA units.
• 😀 Beta-oxidation consists of dehydrogenation, hydration, another dehydrogenation, and cleavage to produce acetyl-CoA, NADH, and FADH2.
• 😀 The process of beta-oxidation is called so because the reactions target the beta-carbon in the fatty acid chain.
• 😀 Each cycle of beta-oxidation cleaves two carbon atoms from the fatty acid, which are released as acetyl-CoA.
• 😀 The energy yield from fatty acid metabolism includes ATP produced from NADH and FADH2, which are generated during beta-oxidation.
• 😀 The calculation of ATP yield from fatty acid oxidation can be determined using the formula: Total ATP = (Acetyl-CoA × 12 ATP) + (NADH × 3 ATP) + (FADH2 × 2 ATP), minus the ATP consumed during activation.
• 😀 The example of palmitic acid (16-carbon saturated fatty acid) shows how to calculate the ATP yield, which is 129 ATP after considering the activation energy cost.

Q & A

Why do fatty acids need to be activated before they can undergo degradation?

Fatty acids need to be activated to facilitate their transport into the mitochondria for degradation. This activation involves attaching Coenzyme A (CoA) to the fatty acid, forming acyl-CoA, which is essential for the subsequent breakdown in beta-oxidation.

What role do the transporters like Carnitine Acyltransferase I and II play in fatty acid degradation?

Carnitine Acyltransferase I and II are enzymes that facilitate the transport of acyl-CoA molecules across the mitochondrial membranes. Acyl-CoA cannot directly enter the mitochondria, so these transporters help transfer the fatty acid attached to carnitine into the matrix where beta-oxidation occurs.

What is beta-oxidation, and why is it called so?

Beta-oxidation is the metabolic pathway through which fatty acids are broken down into acetyl-CoA units. It is called 'beta-oxidation' because the reactions occur at the beta-carbon of the fatty acid chain, as per the Greek nomenclature for carbon atoms.

What are the key reactions in the first round of beta-oxidation?

The first round of beta-oxidation includes four key reactions: dehydrogenation (removal of hydrogen atoms), hydration (adding water to form a hydroxyl group), another dehydrogenation, and finally cleavage, which results in the release of an acetyl-CoA molecule and a shortened acyl-CoA.

How does the energy yield from NADH and FADH2 contribute to the overall ATP production?

Each NADH produced in beta-oxidation contributes 3 ATP, and each FADH2 contributes 2 ATP. These high-energy electron carriers enter the electron transport chain to ultimately produce ATP via oxidative phosphorylation.

What happens to the acyl-CoA molecule during beta-oxidation?

During beta-oxidation, the acyl-CoA molecule is progressively shortened by two carbon atoms with each cycle, releasing acetyl-CoA molecules. This process continues until the entire fatty acid chain is converted into acetyl-CoA.

Why do unsaturated fatty acids require different handling in beta-oxidation compared to saturated fatty acids?

Unsaturated fatty acids have one or more double bonds, which affect their beta-oxidation process. These double bonds must first be adjusted (isomerized or reduced) to fit the reaction conditions in beta-oxidation, while saturated fatty acids do not have this complication.

How do the number of carbons in a fatty acid affect the number of acetyl-CoA produced?

The number of acetyl-CoA molecules produced during beta-oxidation depends on the length of the fatty acid chain. For a fatty acid with an even number of carbons, the number of acetyl-CoA molecules is equal to half the number of carbons. For example, a fatty acid with 16 carbons will produce 8 acetyl-CoA molecules.

How does the process of fatty acid activation use ATP, and why is it necessary?

Fatty acid activation consumes 2 ATP molecules to attach Coenzyme A (CoA) to the fatty acid, forming acyl-CoA. This step is crucial because acyl-CoA is the form that can be transported into the mitochondria and undergo beta-oxidation.

What is the overall ATP yield from the beta-oxidation of palmitic acid (C16)?

The overall ATP yield from the beta-oxidation of palmitic acid (C16) is 129 ATP. This includes ATP from acetyl-CoA, NADH, and FADH2 production, minus the 2 ATP used for activation.