Fatty acid degradation
Fatty acid degradation is the process in which
- Lipolysis of and release from adipose tissue
- Activation and transport into mitochondria
- β-oxidation
Lipolysis and release
Initially in the process of degradation, fatty acids are stored in
Activation and transport into mitochondria
Fatty acids must be activated before they can be carried into the
Formation of an activated thioester bond
The enzyme first
The balanced equation for the above is:
RCOO− + CoASH + ATP → RCO-SCoA + AMP + PPi
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, consuming one water molecule in the process. Thus the net reaction becomes:
RCOO− + CoASH + ATP → RCO-SCoA+ AMP + 2Pi
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 conjugated to carnitine acyltransferase I(palmitoyltransferase) I located on the outer mitochondrial membrane
- Acyl carnitine is shuttled inside by a translocase
- Acyl carnitine (such as Palmitoylcarnitine) 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
The mitochondrial oxidation of fatty acids takes place in three major steps:
- β-oxidation occurs to convert fatty acids into 2-carbon acetyl-CoA units.
- Acetyl-CoA enters into TCA cycleto yield generate reduced NADH and reduced FADH2.
- Reduced cofactors NADH and FADH2 participate in the electron transport chain in the mitochondria to yield ATP. There is no direct participation of the fatty acid.
β-oxidation
After activation by ATP, once inside the mitochondria, the β-oxidation of a fatty acids occurs via four recurring steps:
The final product of β-oxidation of an even-numbered fatty acid is acetyl-CoA, the entry molecule for the citric acid cycle.[3] If the fatty acid is an odd-numbered chain, the final product of β-oxidation will be propionyl-CoA. This propionyl-CoA will be converted into intermediate methylmalonyl-CoA and eventually succinyl-CoA, which also enters the TCA cycle.