Beta Oxidation

For beta-oxidation to occur, the fatty acids must first enter the cell through the cell membranethen bind to the coenzyme A (CoA), forming fatty acyl CoA and, in the case of eukaryotic cells, entering the mitochondria, where beta-oxidation occurs.

Where does beta-oxidation occur?

Beta-oxidation occurs in the mitochondria of eukaryotic cells and in the cytosol of prokaryotic cells. However, before this can happen, fatty acids must first enter the cell and, in the case of eukaryotic cells, the mitochondria. In cases where the fatty acid chains are too long to enter the mitochondria, beta-oxidation can also take place in peroxisomes.

First, fatty acid protein transporters allow the fatty acids to cross the cell membrane and enter the cytosol, as the negatively charged fatty acid chains cannot otherwise cross. Then, the enzyme fat acyl-CoA synthase (or FACS) adds a CoA group to the fatty acid chain, converting it to acyl-CoA.

Depending on its length, the acyl-CoA chain will enter the mitochondria in one of two ways:

1. If the acyl-CoA chain is short, it can diffuse freely across the mitochondrial membrane.
2. If the acyl-CoA chain is long, it must be transported across the membrane by the carnitine shuttle. To do this, the enzyme carnitine palmitoyltransferase 1 (CPT1) – bound to the outer mitochondrial membrane – converts the acyl-CoA chain into an acylcarnitine chain, which can be transported across the mitochondrial membrane by carnitine translocase (CAT). Once inside the mitochondria, CPT2, bound to the inner mitochondrial membrane, converts acylcarnitine back to acyl-CoA. At this point, the acyl-CoA is inside the mitochondria and can now undergo beta-oxidation.

As mentioned above, if the acyl-CoA chain is too long to be processed in the mitochondria, it will be broken down by beta oxidation in the peroxisomes. Research suggests that very long acyl-CoA chains are broken down until they are 8 carbons long, after which they are transported and enter the beta-oxidation cycle in mitochondria. Beta-oxidation in peroxisomes produces H ₂ O _{2 in} instead of FADH2 and NADH, producing heat as a result.

Steps of beta-oxidation

Beta-oxidation takes place in four steps: dehydrogenation, hydration, oxidation and thiolysis. Each step is catalysed by a different enzyme.

Briefly, each cycle of this process starts with an acyl-CoA chain and ends with an acetyl-CoA, a FADH2, a NADH and water, and the acyl-CoA chain becomes two carbons shorter. The total energy yield per cycle is 17 ATP molecules (see below for details on the breakdown). This cycle is repeated until two acetyl-CoA molecules are formed as opposed to one acyl-CoA and one acetyl-CoA. The four steps of beta-oxidation are described below and can be seen in the links to the figures at the end of each explanation.

Dehydrogenation

In the first step, acyl-CoA is oxidised by the enzyme acyl CoA dehydrogenase. A double bond is formed between the second and third carbons (C2 and C3) of the acyl-CoA chain which enters the beta-oxidation cycle; the end product of this reaction is trans-ΔΔ ² -enoyl-CoA (trans-delta 2-enoyl CoA). This step uses FAD and produces FADH2, which will enter the citric acid cycle and form ATP to be used as energy. (Note in the figure below that the count of carbon starts on the right-hand side: the rightmost carbon underneath the atom of the oxygen is C1, then C2 on the left forms a double bond with C3, and so on).

Hydration

In the second step, the double bond between C2 and C3 of trans-ΔΔ ² -enoyl-CoA is hydrated, forming the final product L-β-hydroxyacyl CoA, which has a hydroxyl group (OH) at C2, instead of the double bond. This reaction is catalysed by another enzyme: enoyl CoA hydratase. This step requires water.

Oxidation

In the third step, the hydroxyl group at C2 of L-β-hydroxyacyl CoA is oxidised by NAD+ in a reaction that is catalysed by 3-hydroxyacyl-CoA dehydrogenase. The end products are β-ketoacyl CoA and NADH + H. The NADH will enter the citric acid cycle and produce ATP which will be used as energy.

Thiolysis

Finally, in the fourth step, β-ketoacyl CoA is cleaved by a thiol group (SH) from another β-ketoacyl group. molecule of CoA (CoA-SH). The enzyme that catalyses this reaction is β-ketothiolase. Cleavage takes place between C2 and C3; therefore, the end products are an acetyl-CoA molecule with the original first two carbons (C1 and C2) and an acyl-CoA chain two carbons shorter than the original acyl-CoA chain that entered the beta-oxidation cycle.

End of beta-oxidation

In the case of even-numbered acyl-CoA chains, beta-oxidation ends after a four-carbon acyl-CoA chain is broken down into two acetyl-CoA units, each containing two carbon atoms. The acetyl-CoA molecules enter the citric acid cycle to produce ATP.

In the case of odd-numbered acyl-CoA chains, beta-oxidation occurs in the same way except for the last step: instead of a four-carbon acyl-CoA chain breaking down into two acetyl-CoA units, a five-carbon acyl-CoA chain breaks down into a three-carbon propionyl-CoA and a two-carbon acetyl-CoA. Another chemical reaction then converts propionyl-CoA to succinyl-CoA (see figure below), which enters the citric acid cycle to produce ATP.

Energy yield and end products.

Each beta-oxidation cycle produces 1 FADH2, 1 NADH and 1 acetyl-CoA, which in energy terms is equivalent to 17 ATP molecules:

• 1 FADH2 (x 2 ATP) = 2 ATP
• 1 NADH (x 3 ATP) = 3 ATP
• 1 acetyl-CoA (x 12 ATP) = 12 ATP
• Total = 2 + 3 + 12 = 17 ATP

However, the theoretical ATP yield is higher than the actual ATP yield. In reality, the equivalent of approximately 12 to 16 ATP is produced in each beta-oxidation cycle.

In addition to the energy yield, the fatty acyl-CoaA chain is shortened by two carbons with each cycle. Furthermore, beta-oxidation produces large amounts of water; this is beneficial for eukaryotic organisms such as camels, given their limited access to drinking water.