Fatty Acid Oxidation: 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 and transported into mitochondria using carnitine. Beta oxidation involves four steps: oxidation, hydration, further oxidation, and thiolysis, producing Acetyl CoA. Unsaturated fatty acids may require isomerization for proper oxidation. Odd-chain fatty acids yield Acetyl CoA and propanoyl CoA, which is converted to succinyl CoA for the citric acid cycle, generating significant ATP through these metabolic pathways.

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 substrates for glycolysis. The catabolism of glycerol yields one ATP and two NADH molecules, 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 into fatty acyl CoA and carnitine by carnitine acyltransferase 2 (CAT2), effectively shuttling the fatty acids into the mitochondria for beta oxidation.

Beta oxidation itself consists of four repeating steps, where fatty acids are progressively broken down. The first step involves the oxidation of the fatty acyl CoA, converting an alkane (-ane) to an alkene (-ene) through the action of acyl CoA dehydrogenase, which reduces FAD to FADH₂. This introduces a double bond into the fatty acid chain. In the second step, water is added to the alkene, forming an alcohol, facilitated by enoyl CoA hydratase. The third step involves the oxidation of the alcohol to a carbonyl group, carried out by beta-hydroxy acyl CoA dehydrogenase, which converts NAD⁺ to NADH. Finally, in the fourth step, thiolase cleaves off a two-carbon unit as Acetyl CoA and adds CoA to the remaining fatty acid chain, allowing the cycle to repeat.

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, producing five Acetyl CoA molecules. However, if the fatty acid chain has an odd number of carbons, the process may require additional steps to handle the final three-carbon unit, which will be addressed in further detail.

Fatty Acid Oxidation 2

Unsaturated fatty acids undergo beta oxidation, but they may require additional steps due to the configuration of their double bonds. In particular, cis double bonds need to be rearranged to trans configurations for effective oxidation. The ideal position for the double bond during beta oxidation is between the 2nd and 3rd carbon atoms. If the double bond is not in the correct position, an enzyme called isomerase is utilized to shift it. However, this rearrangement does not produce FADH₂ because the initial step of beta oxidation, which typically introduces a double bond and reduces FAD, is bypassed.

When dealing with multiple unsaturations, the process may require the use of NADPH, an electron carrier similar to NADH, to reduce the double bond before proceeding with beta oxidation. This reduction can lead to the formation of FADH₂ in subsequent steps. The outcome of beta oxidation also depends on whether the fatty acid is of even or odd carbon length. Even-numbered fatty acids yield two acetyl CoA molecules from the final four-carbon fragment, while odd-numbered fatty acids produce one acetyl CoA and one propanoyl CoA. The latter requires conversion to succinyl CoA, which is a component of the tricarboxylic acid (TCA) cycle, also known as the Krebs cycle.

To calculate the ATP yield from the oxidation of palmitic acid, a 16-carbon fatty acid, one can use the formula: (number of carbons / 2) - 1 to determine the number of beta oxidation cycles. For palmitic acid, this results in 7 cycles, producing 8 acetyl CoA molecules. Each cycle generates 1 FADH₂ and 1 NADH, leading to a total of 7 FADH₂ (yielding 10.5 ATP) and 7 NADH (yielding 17.5 ATP). The 8 acetyl CoA molecules then enter the TCA cycle, producing additional ATP: 8 FADH₂ (12 ATP), 24 NADH (60 ATP), and 8 ATP or GTP from the cycle itself. The total ATP yield from the complete oxidation of palmitic acid is 108 ATP.

Despite the high energy yield from fatty acids, glucose is often preferred as a primary energy source due to its higher energy content per weight, making it more efficient for immediate energy needs.

Here’s what students ask on this topic:

What is the process of beta oxidation in fatty acid metabolism?

Beta oxidation is a metabolic process where fatty acids are broken down in the mitochondrial matrix to generate Acetyl CoA, which enters the citric acid cycle. The process involves four main steps: oxidation, hydration, further oxidation, and thiolysis. Initially, fatty acids are activated to fatty acyl CoA and transported into the mitochondria using carnitine. During beta oxidation, two-carbon units are removed from the fatty acyl CoA as Acetyl CoA. This process repeats until the entire fatty acid is converted into Acetyl CoA, producing significant amounts of ATP through subsequent metabolic pathways.

How are fatty acids transported into the mitochondria for beta oxidation?

Fatty acids are transported into the mitochondria through a process involving carnitine. First, fatty acids are activated to form fatty acyl CoA, which is then bound to carnitine by the enzyme carnitine acyltransferase 1 (CAT1). This complex is transported into the mitochondrial matrix via an antiporter mechanism, where acylcarnitine is exchanged for free carnitine. Once inside, carnitine acyltransferase 2 (CAT2) converts acylcarnitine back to fatty acyl CoA, releasing carnitine to be reused. This transport mechanism is often referred to as the carnitine shuttle.

What happens to odd-chain fatty acids during beta oxidation?

Odd-chain fatty acids undergo beta oxidation similarly to even-chain fatty acids but yield a different final product. The last cycle of beta oxidation for odd-chain fatty acids produces one Acetyl CoA (2 carbons) and one propanoyl CoA (3 carbons). Propanoyl CoA cannot directly enter the citric acid cycle and must be converted to succinyl CoA. This conversion involves adding a CO₂ molecule, a process that requires ATP. Succinyl CoA then enters the citric acid cycle, allowing the complete oxidation of the odd-chain fatty acid.

How do unsaturated fatty acids undergo beta oxidation?

Unsaturated fatty acids require additional steps for beta oxidation due to the presence of double bonds. If the double bond is in the cis configuration or not in the correct position, enzymes like isomerases and reductases are needed. Isomerases move the double bond to the correct position, while reductases use NADPH to reduce the double bond if necessary. These adjustments ensure that the fatty acid can proceed through the standard beta oxidation pathway. However, these modifications may result in the loss of FADH₂ production in certain steps.

Why is beta oxidation important for energy production?

Beta oxidation is crucial for energy production because it breaks down fatty acids into Acetyl CoA, which enters the citric acid cycle to produce ATP. Fatty acids are a dense energy source, and their oxidation generates significant amounts of ATP. For example, the oxidation of palmitic acid (a 16-carbon fatty acid) produces 108 ATP molecules. This high energy yield is essential for sustaining prolonged activities and maintaining metabolic functions, especially when glucose levels are low.