Food Chemistry and Fish in Nutrition

4.2.2.1.β-Oxidation of saturated fatty acids

Saturated fatty acids are oxidized to acetyl-CoA by β oxidation. It takes place in mitochondria. Five steps are involved and each step involves acy1-CoA derivatives catalyzed by separate enzymes, utilizes NAD⁺ and FAD as coenzymes, and generates ATP. Fatty acid oxidation is an aerobic process, requiring the presence of oxygen.

Step 1. Activation of Fatty Acids

Long chain fatty acids are first converted to an ‘active fatty acid’ or acyl CoA in the cytosol in the presence of ATP, coenzyme A and Mg²⁺ catalyzed by the enzyme acyl-CoA synthase (thiokinase). But activation of lower fatty acids occurs within the mitochondria. Thiokinase is found both inside and outside the mitochondria.

Thiokinase
Fatty acid + ATP + coenzyme A + Mg²⁺ → Acyl CoA + AMP

The presence of inorganic pyrophosphatase ensures that activation goes to completion by facilitating the loss of the additional high-energy phosphate associated with pyrophosphate. Thus, in effect, two high energy phosphates are expended during the activation of each fatty acid molecule.

Acyl-CoA synthetases are found in the endoplasmic reticulum and inside and on the outer membrane of mitochondria. Several acyl-CoA synthetases have been described, each specific for acids of different chain length.

Transport into mitochondria

(i)Transport of smaller fatty acids

Small fatty acids are able to penetrate the inner membrane of mitochondria and become oxidized within the mitochondria.

(ii) Transport of Long-Chain Fatty Acids

Long-chain fatty acids penetrate the inner mitochondrial membrane only as carnitine derivatives.An enzyme, carnitine acyl transferase I, present in outer mitochondrial membrane, converts long-chain acyl CoA to acylcarnitine, which is able to penetrate the inner membrane of mitochondria and gain access to the oxidation system of enzyme.

Carnitine-acyl carnitine translocase present in mitochondria, catalyses the transfer the acyl carnitine into inner membrane. Carnitine acyl transferase II, present in the inner mitochondrial membrane, converts acylcarnitine to long-chain acyl CoA and carnitine. Acyl CoA then undergoes further reactions of β-oxidation.

Step 2. Dehydrogenation of Aceyl CoA

Acyl CoA is dehydrogenated by Aceyl CoA dehydrogenase to form α-β unsaturated acyl CoA. NAD⁺ is the coenzyme. It is converted to NADH + H⁺ which is reoxidised via electron transport chain.

Aceyl CoA dehydrogenase
Acyl CoA + NAD⁺ ↔ α-β unsaturated acyl CoA + NADH +H⁺

Step 3. Conversion of α-β unsaturated acyl CoA to β hydroxyl acyl CoA

α-β unsaturated acyl CoA is converted to β hydroxyl acyl CoA by the addition of a water molecule catalysed by the enzyme enoyl-CoA hydratase.

Enoyl-CoA hydratase.

α-β unsaturated acyl CoA + H₂O↔ β hydroxyl acyl CoA

Step 4. Dehydrogenation at the β-carbon of β-hydroxyacyl CoA

The β-hydroxy derivative undergoes further dehydrogenation on the β-carbon by β-hydroxyacyl-CoA dehydrogenase to form the corresponding β-ketoacyl-CoA compound. In this case, NAD⁺ is the coenzyme involved in the dehydrogenation. The NADH+H⁺ formed is reoxidised via electron transport chain.

β-hydroxyacyl-CoA dehydrogenase

β hydroxyl acyl CoA + NAD⁺↔ β-ketoacyl-CoA + NADH+H⁺

Step 5. Cleavage by thiolase

Finally, β-ketoacyl-CoA is spilt at the 2, 3- position by thiolase (β-ketoacyl-CoA-thiolase), which catalyzes a thiolytic cleavage involving another molecule of CoA. The products of this reaction are acetyl-CoA and an acyl-CoA derivative containing two carbons less than the original acyl-CoA molecule that underwent this oxidation.

Thiolase
β-ketoacyl-CoA ↔ Acetyl-CoA + acyl-CoA

The acyl-CoA formed in the cleavage reaction renters the oxidative pathway at reaction `1.

In this way, a long-chain fatty acid may be degraded completely to acetyl-CoA (C₂ units). In the case of palmitic acid the reactions are repeated 7 times and 8 molecules of acetyl CoA are formed.

Since acetyl-CoA can be oxidized to CO₂ and water via the citric acid cycle, the complete oxidation of fatty acids is achieved.