Free fatty acids in cells must be activated in order to be catabolized in the mitochondria.

First, free fatty acids are linked to coenzyme A via a thioester bond. This reaction, shown below, is catalyzed by Fatty Acyl-CoA ligases that are specific for short-chain, medium-chain, or long-chain fatty acids (Figure 18.14).

R-COO^- + ATP + CoASH <=> Acyl-S-CoA + AMP + PPi ( = -0.8 kJ/mol)

Subsequent hydrolysis of the PPi by pyrophosphatase drives the reaction to the right.

Next, acyl-CoAs outside of the mitochondrion are moved through the inner mitochondrial membrane after transfer of the acyl group to a carnitine in a reaction catalyzed by carnitine acyltransferase I (Figure 18.15). The acyl-carnitine moiety traverses the membrane and the acyl group is reattached to coenzyme A by carnitine acyltransferase II, in a reversal of the previous reaction.

The acyl-CoAs are then oxidized in the mitochondria by the process called -oxidation.

-Oxidation of Fatty Acids