What is Activation offatty acids ?

Fatty acids cannot undergo oxidation in the form in which they are normally present in the body. They must be converted into a form which can be catabolized. This process is called activation and fatty acid is converted into an active intermediate. Fatty acids must be activated in the cytoplasm before being oxidized in the mitochondria. This activation is catalyzed by fatty acyl CoA synthetase. At least three acyl CoA synthetases, each specific for a particular size (length) of fatty acid are known. Let us see what are

1) Acetyl CoA synthetase: This acts on acetate and low molecular weight fatty acids,
2) Medium chain acyl CoA synthetase: This acts on fatty acids with 4- 1 1 carbon atoms, and
3) Acyl CoA synthetase: This acts on fatty acids with 6 to 20 carbon atoms.

The activity of acetyl CoA synthetase in muscles is restricted to the mitochondrial matrix. The medium-chain acyl CoA synthetase occurs only in liver mitochondria, where medium chain fatty acids (obtained from digestion ofdietary triacylglycerols and transported by the portal blood) are metabolized. Acyl CoA synthetase, the major activating enzyme, occurs on the outer mitochondrial membrane surface and in endoplasmic reticulum.

Activation of fatty acids results in the formation of an ester between the carboxyl (COOH) group of the fatty acid and SH group of the coenzyme A, forming fatty acid ester of coenzyme A. The overall reaction of activation is:

(fatty acid) (fatty acyl CoA)

The reaction favors the creation of fatty acyl CoA, as the pyrophosphate formed is hydrolyzed through the enzyme pyrophosphatase:PP,+ $0 --+ 2P,
Therefore, activation of a fatty acid molecule requires expenditure of two high-energy 196 phosphate bonds.