Question

What is the structure of the partially oxidized fatty acyl group that is formed when oleic acid, \(18: 1\left(\Delta^{9}\right)\), has undergone three cycles of \(\beta\) oxidation? What are the next two steps in the continued oxidation of this intermediate?

Short answer

After three cycles of β-oxidation, a 12:1(Δ³) fatty acyl remains. Next steps are enoyl-CoA isomerase and hydration of the new trans double bond.

Step-by-step solution

Understanding Beta-Oxidation

Beta-oxidation is the process of breaking down fatty acids in the mitochondria to produce acetyl-CoA units. Each cycle of beta-oxidation removes a two-carbon unit from the fatty acid, converting it to acetyl-CoA.

Initial Structure of Oleic Acid

Oleic acid is an 18-carbon fatty acid with one double bond between the ninth and tenth carbons, denoted as 18:1(Δ⁹). Its structure includes a long hydrocarbon chain with a carboxylic acid group at one end.

First Cycle of Beta-Oxidation

A two-carbon acetyl-CoA group is cleaved from the oleic acid, reducing the hydrocarbon chain from 18 to 16 carbons long. The remaining structure is 16:1(Δ⁷), with the double bond now located between the seventh and eighth carbon.

Second Cycle of Beta-Oxidation

Another two-carbon acetyl-CoA is removed. The fatty acid chain now shortens to 14 carbons, 14:1(Δ⁵), with the double bond between the fifth and sixth carbon.

Third Cycle of Beta-Oxidation

Another acetyl-CoA group is cleaved, resulting in a 12-carbon fatty acyl group, 12:1(Δ³), with the double bond shifted to between the third and fourth carbon.

Next Step - Enoyl-CoA Isomerase

After the third cycle, the next step is the use of enoyl-CoA isomerase, which converts the cis-Δ³ double bond into a trans configuration, forming trans-Δ²-dodecenoyl-CoA.

Next Step - Hydration of Trans-Δ²-dodecenoyl-CoA

The trans double bond is hydrated by enoyl-CoA hydratase, adding water across the double bond to produce a hydroxyl group on the beta carbon, forming L-3-hydroxy-dodecanoyl-CoA.

Key concepts

Structure of Oleic Acid

Oleic acid is a monounsaturated omega-9 fatty acid commonly found in various animal and vegetable fats and oils. It is designated as an 18-carbon fatty acid with the notation 18:1(Δ⁹), indicating it has 18 carbons and one double bond located between the 9th and 10th carbon atoms. The structure of oleic acid features a linear chain of carbon atoms, with a carboxylic acid group (-COOH) at one end. The position of the double bond is crucial as it dictates the geometry and chemical behavior of the molecule. In the case of oleic acid, the double bond is in the cis configuration, which introduces a kink in the molecule, affecting how it interacts with other fatty acids and membranes. This structure is a basis for its partial oxidation in metabolic processes like beta-oxidation.

Acetyl-CoA Formation

In the process of beta-oxidation, long-chain fatty acids like oleic acid are broken down into two-carbon units known as acetyl-CoA. Each cycle of beta-oxidation removes a two-carbon fragment from the carboxyl end of the fatty acid chain.
The initial structure of oleic acid, containing 18 carbons, undergoes successive splitting through beta-oxidation. After three cycles of beta-oxidation, it yields three acetyl-CoA molecules and leaves a 12-carbon fatty acyl group.
Acetyl-CoA is a central metabolic intermediate, important for energy production. Once formed, it enters the citric acid cycle, where it is further oxidized for energy in the form of ATP. Thus, acetyl-CoA formation in beta-oxidation is critical for fueling cellular energy production.

Enoyl-CoA Isomerase Activity

After three cycles of beta-oxidation, oleic acid has been reduced to a 12-carbon fatty acyl group referred to as 12:1(Δ³). The next step involves the enzyme enoyl-CoA isomerase, which plays a vital role in adjusting the position and geometry of double bonds in unsaturated fatty acids.
This enzyme specifically converts the cis-Δ³ double bond into a trans-Δ² configuration. This is essential because beta-oxidation enzymes can only process trans-configured substrates. By repositioning the double bond, enoyl-CoA isomerase makes the fatty acyl group suitable for the subsequent steps of oxidation, thereby facilitating continued breakdown and energy extraction from the fatty acid.

Enoyl-CoA Hydratase Function

With the double bond now in a trans-Δ² configuration, the next step in beta-oxidation involves the action of enoyl-CoA hydratase. This enzyme catalyzes the addition of a water molecule across the double bond, turning it into a hydroxy group on the beta-carbon.
Through this hydration reaction, trans-Δ²-dodecenoyl-CoA is transformed into L-3-hydroxy-dodecanoyl-CoA. This newly formed molecule is equipped with a hydroxyl group, setting the stage for further metabolic conversions.

• Hydration provides specificity, ensuring steps occur sequentially and correctly in metabolic pathways.
• The product of this step is essential for the next oxidation step, converting the hydroxy group into a keto group.

These transformations are critical as they facilitate the complete oxidation of fatty acids, enabling the release of stored energy.