Beta Oxidation

Beta Oxidation Definition

In beta oxidation, fatty acid molecules are broken down to produce energy through multiple steps. The beta oxidation process breaks down long fatty acids that have been converted into acyl-CoA chains into progressively smaller fatty acyl-CoA chains. As a result of this reaction, acetyl-CoA, FADH2 and NADH are released, the three of which then enter a metabolic process called the citric acid cycle or Krebs cycle, where ATP is produced. 

The beta oxidation process continues until two acetyl-CoA molecules are produced and the acyl-CoA chain has been completely broken down. Eukaryotic cells undergo beta oxidation in the mitochondria, while prokaryotic cells undergo it in the cytosol.

In eukaryotic cells, beta oxidation occurs in the mitochondria after fatty acids bind to coenzyme A (CoA) and enter the cell membrane.

Where Does Beta Oxidation Occur?

In eukaryotic cells, beta oxidation occurs in the mitochondria, while in prokaryotic cells, it occurs in the cytosol. Fatty acids must first enter the cell and, in eukaryotic cells, the mitochondria before this can happen. Beta oxidation can also occur in peroxisomes when fatty acid chains are too long to enter mitochondria.

Due to the negatively charged fatty acid chains, fatty acids cannot cross the cell membrane without fatty acid protein transporters. A CoA group is added to the fatty acid chain by the enzyme fatty acyl-CoA synthase (or FACS).

A chain of acyl-CoA can enter mitochondria in one of two ways, depending on its length:

1. It is possible for the acyl-CoA chain to freely diffuse through the mitochondrial membrane if it is short.
2. A long acyl-CoA chain must be transported across the membrane by the carnitine shuttle. The enzyme carnitine palmitoyltransferase 1 (CPT1) converts the acyl-CoA chain into an acylcarnitine chain, which can be transported across the mitochondrial membrane by the carnitine translocase (CAT). CPT2, bound to the inner mitochondrial membrane, converts acylcarnitine back to acyl-CoA once inside the mitochondria. Having reached the mitochondria, acyl-CoA can now undergo beta oxidation.

The acyl-CoA chain will be broken down by beta oxidation in the peroxisomes if it is too long to be processed in the mitochondria. In the mitochondria, very long acyl-CoA chains are broken down until they are eight carbons long, at which point they enter the beta oxidation cycle. Peroxisomes produce heat when beta oxidation produces H2O2 instead of FADH2 and NADH.

Beta Oxidation Steps

The beta oxidation process involves four steps: dehydrogenation, hydration, oxidation, and thyolisis. Each step is catalyzed by a different enzyme.

Each cycle of this process begins with an acyl-CoA chain and ends with one acetyl-CoA, one FADH2, one NADH and water, and the acyl-CoA chain is two carbons shorter. There are 17 ATP molecules in total per cycle (see the breakdown below). 

As opposed to one acyl-CoA and one acetyl-CoA, two acetyl-CoA molecules are formed. At the end of each explanation, links to the figures illustrate the four steps of beta oxidation.

Dehydrogenation

A acyl-CoA dehydrogenase enzyme oxidizes acyl-CoA in the first step. As the acyl-CoA chain enters the beta oxidation cycle, a double bond is formed between the second and third carbons (C2 and C3); the result is trans-Δ2-enoyl-CoA (trans-delta 2-enoyl CoA). In this step, FAD is converted into FADH2, which enters the citric acid cycle to form ATP. The carbon count starts on the right side: C1 is the rightmost carbon below the oxygen atom, followed by C2 on the left and C3 on the right.

Hydration

During the second step, the double bond between C2 and C3 of trans-2-enoylcoA is hydrated, resulting in the end product l-hydroxyacylcoA, which has an hydroxyl group (OH) in C2. An enzyme called enoyl CoA hydratase catalyzes this reaction. Water is required for this step.

Oxidation

The hydroxyl group is oxidized by NAD+ through 3-hydroxyacyl-CoA dehydrogenase in the third step. At the end of the reaction, it produces β-ketoacyl CoA and NADH + H. This produces ATP, an energy source.

Thiolysis

Lastly, β-ketoacyl CoA is cleaved by a thiol group (SH) of another CoA molecule (CoA-SH). The enzyme responsible for catalyzing this reaction is β-ketothiolase. Due to the cleavage between C2 and C3, the end products are acetyl-CoA molecules with the original two first carbons (C1 and C2) and acyl-CoA chains that are two carbons shorter than the original acyl-CoA chains.

End of Beta Oxidation

When an even-numbered acyl-CoA chain is broken into two acetyl-CoA units, each containing two carbon atoms, beta oxidation ends. ATP is produced by entering the citric acid cycle with acetyl-CoA molecules.

As with even-numbered acyl-CoA chains, beta oxidation takes place in the same way except at the last step: instead of a four-carbon acyl-CoA chain being broken down into two acetyl-CoA units, a five-carbon acyl-CoA chain is broken down into a three-carbon propionyl-CoA and a two-carbon acetyl-CoA. In the citric acid cycle, ATP is produced by converting propionyl-CoA into succinyl-CoA.

Energy Yield and End Products

A beta oxidation cycle yields one FADH2, one NADH, and one acetyl-CoA, which is equivalent to 17 ATP molecules:

• It is equal to 2 ATP when FADH2 is multiplied by 2 ATP
• A NADH molecule (x 3 ATP) equals 3 ATP molecules
• 12 ATP = 1 acetyl-CoA
• Two plus three plus twelve equals seventeen ATP

Real ATP yields are lower than theoretical ATP yields. Each beta oxidation cycle produces about 12 to 16 ATPs.

Aside from energy production, fatty acyl-CoaA chains become two carbons shorter with each cycle. Additionally, beta oxidation produces large quantities of water, which are beneficial to eukaryotic organisms like camels, which do not have easy access to drinkable water.

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