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 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 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.
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 cycle to yield generate reduced NADH and reduced FADH.
# Reduced cofactors NADH and FADH participate in the electron transport chain in the mitochondria to yield ATP. There is no direct participation of the fatty acid.