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6.5.1.1.1 Activation of Fatty Acids
Fatty acids must first be converted in a reaction with ATP to an active intermediate before they will react with the enzymes responsible for their further metabolism. In the presence of ATP and coenzyme A, the enzyme acyl-CoA synthetase (thiokinase) catalyzes the conversion of a fatty acid (or free fatty acid) to an “active fatty acid” or acyl-CoA, accompanied by the expenditure of one high-energy phosphate.
Acyl-CoA synthetase
Fatty acid +ATP+CoA -->Acy1-CoA + PPi + AMP
In effect, two high energy phosphates are expended during the activation of each fatty acid molecule. Acyl-CoA synthetases are found in the endoplasmic reticulum and inside and on the outer membrane of mitochondria. Although fatty acids are activated for oxidation in the cytosol, the oxidation takes place inte mitochondria.
Transport of Long-Chain Fatty Acids into mitochondria Long-chain fatty acids cannot penetrate the inner mitochondrial membrane. Instead, its acyl portion is first transferred to carnitine. Carnitine (3-hydroxy 4-trimethylammoium butyrate) (CH3)3N+-CH2-CH(OH)-CH2-COO-, is widely disturbed and is particularly abundant in plant and animal tissues.
Activation of lower fatty acids, and their oxidation within the mitochondria, may occur independently of carnitine. An enzyme, carnitine palmityltransferase I, present in outer mitochondrial membrane, converts long-chain acyl CoA to acylcarnitine, which is able to penetrate the inner membrane of mitochondria and gain access to the oxidation system of enzyme. Carnitine acylcarnitine translocase acts as an inner enzyme and transport of fatty acids.
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