Fatty acid degradation

Fatty acid degradation is the process in which fatty acids are broken down into their metabolites, resulting in release of its energy to the target cells. It includes three major steps:

• Lipolysis of and release from adipose tissue,
• Activation and transport into mitochondria,
• β-oxidation

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Lipolysis and release

Initially in the process of degradation, fatty acids are stored in fat cells (adipocytes). The breakdown of this fat is known as lipolysis. The products of lipolysis, free fatty acids, are released into the bloodstream and circulate throughout the body.

Activation and transport into mitochondria

Fatty acids must be activated before they can be carried into the mitochondria, where fatty acid oxidation occurs. This process occurs in two steps catalyzed by the enzyme fatty acyl-CoA synthetase.

Formation of an activated thioester bond

The enzyme first catalyzes nucleophilic attack on the α-phosphate of ATP to form pyrophosphate and an acyl chain linked to AMP. The next step is formation of an activated thioester bond between the fatty acyl chain and Coenzyme A.

The formula for the above is:

RCOO- + CoA + ATP + H2O → RCO-CoA + AMP + PPi + 2H+

This two-step reaction is freely reversible and its equilibrium lies near 1. To drive the reaction forward, the reaction is coupled to a strongly exergonic hydrolysis reaction: the enzyme inorganic pyrophosphatase cleaves the pyrophosphate liberated from ATP to two phosphate ions. Thus the net reaction becomes:

RCOO- + CoA + ATP + H2O → RCO-CoA + AMP + 2Pi + 2H+

Transport into the mitochondrial matrix

The inner mitochondrial membrane is impermeable to fatty acids and a specialized carnitine carrier system operates to transport activated fatty acids from cytosol to mitochondria.

Once activated, the acyl CoA is transported into the mitochondrial matrix. This occurs via a series of similar steps:

1. Acyl CoA is conjugated to carnitine by carnitine acyltransferase (palmitoyltransferase) I located on the outer mitochondrial membrane
2. Acyl carnitine is shuttled inside by a translocase
3. Acyl carnitine is converted to acyl CoA by carnitine acyltransferase (palmitoyltransferase) II located on the inner mitochondrial membrane. The liberated carnitine returns to the cytosol.

It is important to note that carnitine acyltransferase I undergoes allosteric inhibition as a result of malonyl-CoA, an intermediate in fatty acid biosynthesis, in order to prevent futile cycling between beta-oxidation and fatty acid synthesis.

β-oxidation

Main article: Beta oxidation

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

1. Oxidation by FAD
2. Hydration
3. Oxidation by NAD⁺
4. Thiolysis