Fatty Acid Oxidation 1: Videos & Practice Problems

Fats serve as energy storage, breaking down into glycerol and fatty acids, which convert to Acetyl CoA via beta oxidation. Fatty acids must first be activated to fatty acyl CoA, then transported into the mitochondrial matrix using the carnitine shuttle. Beta oxidation involves four steps: oxidation, hydration, further oxidation, and thiolysis, producing Acetyl CoA. Each cycle removes two carbon units, with the process repeating until the fatty acid is fully oxidized. Understanding these metabolic pathways is crucial for grasping energy production and utilization in biological systems.

Fatty Acid Oxidation 1

Fats serve as a crucial source of energy storage in the body, being broken down into glycerol and fatty acids. Fatty acids can be converted into Acetyl CoA through a process known as beta oxidation, which occurs in the mitochondria. Before delving into beta oxidation, it's important to understand how fatty acids enter the mitochondria. Interestingly, fats also play a role in water storage, particularly in desert-dwelling animals like camels, whose humps are filled with fat that can be converted into water.

Glycerol, a component of fats, can be converted into dihydroxyacetone phosphate (DHAP) and subsequently into glyceraldehyde-3-phosphate (G3P), both of which are intermediates in glycolysis. The catabolism of glycerol yields one ATP and two NADH molecules per glycerol, making it a non-fermentable sugar due to the excess NADH produced, which cannot be efficiently utilized in fermentation processes.

To enter the citric acid cycle, fatty acids must first be activated to form fatty acyl CoA, a process that costs the equivalent of two ATP molecules. This activation involves the addition of coenzyme A (CoA) to the fatty acid. The activated fatty acyl CoA is then transported into the mitochondrial matrix, where it binds to carnitine via the enzyme carnitine acyltransferase 1 (CAT1). This process is facilitated by an antiporter that exchanges acylcarnitine for free carnitine. Once inside the matrix, acylcarnitine is converted back to fatty acyl CoA and carnitine by carnitine acyltransferase 2 (CAT2), effectively shuttling the fatty acids into the mitochondria for beta oxidation.

Beta oxidation itself involves the systematic removal of two-carbon units from the fatty acyl CoA, producing Acetyl CoA. This process consists of four repeating steps: first, the fatty acid is oxidized to introduce a double bond, facilitated by acyl CoA dehydrogenase, which reduces FAD to FADH₂. Next, water is added to form an alcohol, catalyzed by enoyl CoA hydratase. The alcohol is then oxidized to a carbonyl group by beta-hydroxy acyl CoA dehydrogenase, converting NAD⁺ to NADH. Finally, thiolase cleaves off Acetyl CoA and adds CoA to the remaining fatty acid chain, allowing the cycle to repeat until the entire fatty acid is broken down.

For a fatty acid chain with an even number of carbons, the number of cycles through beta oxidation is calculated as half the number of carbons minus one. For example, a 10-carbon fatty acid would undergo five rounds of beta oxidation, yielding five Acetyl CoA molecules. However, in cases where the fatty acid chain has an odd number of carbons, the process may require additional steps to fully metabolize the fatty acid, leading to variations in the expected outcomes of beta oxidation.

Here’s what students ask on this topic:

What is the role of carnitine in fatty acid oxidation?

Carnitine plays a crucial role in transporting fatty acids into the mitochondrial matrix for beta oxidation. Fatty acids are first activated to fatty acyl CoA, which then binds to carnitine via carnitine acyltransferase 1 (CAT1) to form acylcarnitine. This acylcarnitine is transported into the mitochondrial matrix through an antiporter, which simultaneously moves free carnitine out. Once inside, carnitine acyltransferase 2 (CAT2) converts acylcarnitine back to fatty acyl CoA and free carnitine, allowing the fatty acyl CoA to undergo beta oxidation. This process is often referred to as the carnitine shuttle.

What are the four steps of beta oxidation?

Beta oxidation consists of four repeating steps:

1. Oxidation: Fatty acyl CoA is oxidized by acyl CoA dehydrogenase, converting FAD to FADH₂ and forming a double bond.
2. Hydration: Enoyl CoA hydratase adds water to the double bond, forming an alcohol.
3. Further Oxidation: The alcohol is oxidized by beta-hydroxyacyl CoA dehydrogenase, converting NAD⁺ to NADH and forming a carbonyl group.
4. Thiolysis: Thiolase cleaves the carbonyl group, releasing acetyl CoA and attaching a new CoA to the remaining fatty acid chain.

This cycle repeats until the entire fatty acid is converted to acetyl CoA units.

How are fatty acids activated before entering the mitochondria?

Fatty acids are activated by being converted into fatty acyl CoA. This activation involves the enzyme acyl CoA synthetase, which attaches a CoA molecule to the fatty acid. The reaction consumes 1 ATP, but since both anhydride bonds are broken, it is often considered to cost 2 ATP. The resulting fatty acyl CoA is then ready to be transported into the mitochondrial matrix via the carnitine shuttle for beta oxidation.

What happens to glycerol during fat metabolism?

During fat metabolism, glycerol is converted into dihydroxyacetone phosphate (DHAP), which is then converted into glyceraldehyde-3-phosphate (G3P). Both DHAP and G3P are intermediates in glycolysis. The catabolism of glycerol yields 1 ATP and 2 NADH per glycerol molecule. However, due to the high NADH production, glycerol is not suitable for fermentation as it produces more NADH than can be utilized, making it an unsustainable sugar for this process.

What is the significance of beta oxidation in energy production?

Beta oxidation is crucial for energy production as it breaks down fatty acids into acetyl CoA, which enters the citric acid cycle to produce ATP. Each cycle of beta oxidation removes two carbon units from the fatty acid, generating acetyl CoA, NADH, and FADH₂. These molecules are essential for the electron transport chain, where they contribute to the production of a significant amount of ATP, making beta oxidation a vital process for energy utilization in biological systems.