Beta Oxidation Definition
Beta oxidation is a metabolic process involving multiple steps by which fatty acid molecules are broken down to produce energy. It involves the oxidation of the beta-carbon of the fatty acid to a carbonyl group and the removal of successive two-carbon fragments from the fatty acid. This process occurs in the mitochondria and/or in peroxisomes, and results in the production of acetyl-CoA molecules.
Where Does Beta Oxidation Occur?
Beta oxidation is the process of breaking down fatty acids into smaller molecules, such as acetyl-CoA, for energy production. It occurs in the mitochondria of eukaryotic cells and in the cytosol of prokaryotic cells.
Before beta-oxidation can take place, fatty acids must first enter the cell and, in the case of eukaryotic cells, enter the mitochondria. During beta-oxidation, two carbon atoms are removed from an acyl-CoA chain at a time to form an acetyl-CoA molecule.
This process continues until all carbons have been completely broken down. In addition to fatty acids, some prostaglandins and leukotrienes also undergo initial oxidation in peroxisomes until octanoyl-CoA is formed before entering mitochondrial oxidation.
Beta oxidation ends after a four-carbon acyl-CoA chain is broken down into two acetyl-CoA units, each one containing two carbon atoms. Acetyl-CoA molecules then enter the citric acid cycle to yield ATP.
Beta Oxidation Steps
Beta oxidation consists of four steps: dehydrogenation, hydration, oxidation, and thiolysis. Each step is catalyzed by a distinct enzyme.
Dehydrogenation is a step in the beta-oxidation pathway, which is the process of breaking down fatty acids to produce energy. In this step, FAD (flavin adenine dinucleotide) accepts two protons and two electrons from acyl-CoA to form FADH2.
This results in a double bond between C2 and C3. Acyl-CoA dehydrogenase catalyzes this reaction. The oxidation power of FAD is required to oxidize the alkyl chain, much as it is in the succinate dehydrogenase reaction of the tricarboxylic acid cycle.
Beta-oxidation takes place in four steps: dehydrogenation, hydration, oxidation, and thiolysis. Each step is catalyzed by a distinct enzyme. Dehydrogenation by acyl-CoA dehydrogenase is the first step in beta-oxidation. The enzyme catalyzes the formation of a double bond between C-2 and C-3.
Hydration is the second step of beta-oxidation, in which a water molecule attacks the double bond of the fatty acid, resulting in a hydroxyl group at C3. This reaction is catalyzed by enoyl-CoA hydratase.
Beta oxidation takes place in four steps: dehydrogenation, hydration, oxidation, and thiolysis. Each step is catalyzed by a distinct enzyme. The end result of beta-oxidation is acetyl-CoA molecules that enter the citric acid cycle to yield ATP.
Beta oxidation can generate up to 129 ATP molecules from one molecule of palmitic acid (a 16-carbon fatty acid). Chains with an even number of carbons are broken down into two acetyl-CoA units, each containing two carbon atoms.
In contrast, chains with an odd number of carbons are oxidized in the same manner as even-numbered chains but produce propionyl-CoA and acetyl-CoA as final products.
Propionyl-CoA is first carboxylated using a bicarbonate ion into the D-stereoisomer of methyl malonyl-CoA before it enters the citric acid cycle.
In the third step, the hydroxyl group in C2 of L-β-hydroxy acyl CoA is oxidized by NAD+ in a reaction that is catalyzed by 3-hydroxy acyl-CoA dehydrogenase. The end products are β-ketoacyl CoA and NADH + H. NADH will enter the citric acid cycle and produce ATP that will be used as energy.
Thiolysis is the fourth step in fatty acid beta-oxidation, which is a metabolic pathway that breaks down long-chain fatty acids into acetyl-CoA molecules.
This step involves the cleavage of the thioester bond between C2 and C3 (alpha and beta carbons) of 3-ketoacyl CoA by thiolase enzyme, releasing two carbon units as acetyl CoA and a fatty acyl CoA minus two carbons.
The shortened acyl-CoA then reenters the beta-oxidation pathway. During this process, NADH and FADH2 are produced by both beta-oxidation and the TCA cycle, which are used by the mitochondrial electron transport chain to produce ATP.
End of Beta Oxidation
The final step in beta-oxidation involves cleavage of the bond between the alpha and beta carbon by CoASH. This step is catalyzed by beta-keto thiolase and is a thiolytic reaction. The reaction produces one molecule of acetyl CoA and a fatty acyl CoA that is two carbons shorter.
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 one containing two carbon atoms. Acetyl-CoA molecules enter the citric acid cycle to yield ATP.
Purpose Of Beta Oxidation
Beta oxidation is a metabolic process that breaks down fatty acids to produce energy. The process occurs in eukaryotic cells in the mitochondria and in prokaryotic cells in the cytosol.
Fatty acids must first enter the cell through the cell membrane, then bind to coenzyme A (CoA), forming fatty acyl CoA, and, in the case of eukaryotic cells, enter the mitochondria where beta-oxidation occurs.
The purpose of beta-oxidation is to generate energy from fatty acids. During inter-prandial periods and high energy demand states such as exercise, beta-oxidation is a significant source of metabolic energy.
The process involves four main enzymes: acyl-CoA dehydrogenase, enoyl-CoA hydratase, hydroxy acyl-CoA dehydrogenase, and ketoacyl-CoA thiolase.
Acyl-CoA dehydrogenase creates a double bond between the second and third carbons down from the CoA group on acyl-CoA and produces a shortened acyl-CoA that re-enters the beta-oxidation pathway.
Acetyl-CoA generated by beta-oxidation enters the mitochondrial TCA cycle where it is further oxidized to generate NADH and FADH2. The NADH and FADH2 produced by both beta-oxidation and the TCA cycle are used by the mitochondrial electron transport chain to produce ATP.
Inhibition of ACC2 can lead to an increase in fatty acid β-oxidation while inhibition of ACC1 decreases fatty acid biosynthesis.
Energy Yield and End Products
Each beta-oxidation cycle yields 1 FADH2, 1 NADH, and 1 acetyl-CoA, which in terms of energy 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 real ATP yield. In reality, the equivalent of about 12 to 16 ATPs is produced in each beta-oxidation cycle.
Besides energy yield, the fatty acyl-CoaA chain becomes two carbons shorter with each cycle. In addition, beta-oxidation yields great amounts of water; this is beneficial for eukaryotic organisms such as camels given their limited access to drinkable water.