Beta oxidation

  Beta oxidation is the process by which fatty acids, in the form of Acyl-CoA molecules, are broken down in the mitochondria and/or in peroxisomes to generate Acetyl-CoA, the entry molecule for the Krebs Cycle.

Occurs in mitochondrial matrix.

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Activation of fatty acids

Free fatty acids can penetrate the plasma membrane due to their poor water solubility and high fat solubility. Once in the cytosol, a fatty acid reacts with ATP to give a fatty acyl adenylate, plus inorganic pyrophosphate. This reactive acyl adenylate then reacts with free coenzyme A to give a fatty acyl-CoA ester plus AMP.

Four recurring steps

Once inside the mitochondria, the β-oxidation of fatty acids occurs via four recurring steps:

This process continues until the entire chain is cleaved into acetyl CoA units. For every cycle, the Acyl CoA unit is shortened by two carbon atoms. Concomitantly, one molecule of FADH₂, NADH and acetyl CoA are formed.

β-oxidation of unsaturated fatty acids

β-oxidation of unsaturated fatty acids poses a problem since the location of a cis bond can prevent the formation of a trans-δ² bond. These situations are handled by an additional two enzymes.

Whatever the conformation of the hydrocarbon chain, β-oxidation occurs normally until the acyl CoA (because of the presence of a double bond) is not an appropriate substrate for acyl CoA dehydrogenase, or enoyl CoA hydratase:

• If the acyl CoA contains a cis-Δ³ bond, then cis-δ³-Enoyl CoA isomerase will convert the bond to a trans-Δ² bond, which is a regular substrate.

• If the acyl CoA contains a cis-Δ⁴ double bond, then its dehydrogenation yields a 2,4-dienoyl intermediate, which is not a substrate for enoyl CoA hydratase. However, the enzyme 2,4 Dienoyl CoA reductase reduces the intermediate, using NADPH, into trans-Δ³-enoyl CoA. As in the above case, this compound is converted into a suitable intermediate by cis-Δ³-Enoyl CoA isomerase.

To summarize:

• odd numbered double bonds are handled by the isomerase.
• even numbered bonds by the reductase (which creates an odd numbered double bond) and the isomerase.

β-oxidation of odd-numbered chains

Chains with an odd-number of carbons are oxidized in the same manner as even-numbered chains, but the final products are propionyl CoA and acetyl CoA.

Propionyl CoA is converted into succinyl CoA (which is an intermediate in the citric acid cycle) in a reaction that involves Vitamin B12. Succinyl CoA can then enter the citric acid cycle.

Because it cannot be completely metabolized in the citric acid cycle, the products of its partial reaction must be removed in a process called cataplerosis. This allows regeneration of the citric acid cycle intermediates, possibly an important process in certain metabolic diseases.

Oxidation in peroxisomes

Fatty acid oxidation also occurs in peroxisomes. However, the oxidation ceases at octanyl CoA.

One significant difference is that oxidation in peroxisomes is not coupled to ATP synthesis. Instead, the high-potential electrons are transferred to O₂, which yields H₂O₂. The enzyme catalase, found exclusively in peroxisomes, converts the hydrogen peroxide into water and oxygen. It is believed that very long chain (C-22)fatty acids undergo initial oxidation in peroxisomes which is followed by mitochondrial oxidation. Peroxisomal oxidation is induced by high fat diet and administration of hypolipidemic drugs like clofibrate.

Energy yield

The ATP yield for every oxidation cycle is 14 ATP, broken down as follows:

For an even-numbered saturated fat (C_2n), n - 1 oxidations are necessary and the final process yields an additional acetyl CoA. In addition, two equivalents of ATP are lost during the activation of the fatty acid. Therefore, the total ATP yield can be stated as:

(n - 1) * 14 + 10 - 2 = total ATP

For instance, the ATP yield of palmitate (C₁₆, n = 8) is:

(8 - 1) * 14 + 10 - 2 = 106 ATP

Represented in table form:

For sources that use the larger ATP production numbers described above, the total would be 129 ATP equivalents per palmitate.

See also

• Fatty acid metabolism
• Krebs cycle
• Omega oxidation