Β-oxidation

Metabolic process involving the breakdown of fatty acids

Template:Infobox metabolic pathway

β-Oxidation is a metabolic process involving the breakdown of fatty acids into acetyl-CoA units, which can then enter the citric acid cycle to produce ATP, the energy currency of the cell. This process occurs in the mitochondria of eukaryotic cells and in the peroxisomes of some organisms.

Overview

β-Oxidation is a crucial part of lipid metabolism, allowing organisms to convert stored fat into usable energy. The process involves several steps, each catalyzed by specific enzymes, and results in the sequential removal of two-carbon units from the fatty acid chain.

Steps of β-Oxidation

The β-oxidation pathway consists of four main steps:

1. Dehydrogenation

The first step involves the oxidation of the fatty acyl-CoA by the enzyme acyl-CoA dehydrogenase, which introduces a double bond between the β and α carbon atoms, forming a trans-Δ²-enoyl-CoA. This reaction reduces FAD to FADH2.

2. Hydration

The second step is the hydration of the double bond by the enzyme enoyl-CoA hydratase, resulting in the formation of L-β-hydroxyacyl-CoA.

3. Dehydrogenation

The third step involves the oxidation of L-β-hydroxyacyl-CoA by β-hydroxyacyl-CoA dehydrogenase, producing β-ketoacyl-CoA and reducing NAD+ to NADH.

4. Thiolysis

The final step is the cleavage of β-ketoacyl-CoA by thiolase, which releases a molecule of acetyl-CoA and a fatty acyl-CoA that is two carbons shorter. This shorter acyl-CoA re-enters the β-oxidation cycle.

Energy Yield

The complete oxidation of a fatty acid molecule through β-oxidation and subsequent entry into the citric acid cycle results in the production of a significant amount of ATP. For example, the oxidation of palmitic acid (C16) yields 106 molecules of ATP.

Regulation

β-Oxidation is tightly regulated by the availability of substrates and the energy needs of the cell. Key regulatory points include the transport of fatty acids into the mitochondria via the carnitine shuttle and the inhibition of acyl-CoA dehydrogenase by high levels of NADH and acetyl-CoA.

Clinical Significance

Defects in the enzymes involved in β-oxidation can lead to metabolic disorders such as medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). These conditions can result in hypoglycemia, muscle weakness, and other symptoms due to impaired fatty acid metabolism.

Also see

• Fatty acid metabolism
• Citric acid cycle
• Electron transport chain
• Gluconeogenesis
• Ketogenesis