Everything about Fatty Acid Degradation totally explained
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
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 + H
2O → RCO-CoA + AMP + PP
i + 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 + H
2O → 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:
Acyl CoA is conjugated to carnitine by carnitine acyltransferase (palmitoyltransferase) I located on the outer mitochondrial membrane
Acyl carnitine is shuttled inside by a translocase
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
Once inside the mitochondria, the β-oxidation of fatty acids occurs via four recurring steps:
Oxidation by FAD
Hydration
Oxidation by NAD+
ThiolysisFurther Information
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