| ACTIVATION OF FATTY ACIDS AND THEIR TRANSPORT TO THE MITOCHONDRION
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Fatty acids do not exist in free form in the body - they are soaps, and would dissolve membranes. In blood, fatty acids are bound to albumin, which is present at ∼0.5 mmol/L concentration (35 mg/mL) in plasma. Each molecule of albumin can bind six to eight fatty acid molecules. In the cytosol, fatty acids are bound to a series of fatty-acid-binding proteins and enzymes. As the priming step for their catabolism, the fatty acids are activated to their CoA derivative, using adenosine triphosphate (ATP) as the energy source (Fig. 14.1). The carboxyl group is first activated to an enzyme-bound, high-energy acyl adenylate intermediate, formed by reaction of the carboxyl group of the fatty acid with ATP. The acyl group is then transferred to CoA by the same enzyme, fatty acyl CoA synthetase. This enzyme is commonly known as fatty acid thiokinase, because ATP is consumed in the formation of the thioester bond in acyl CoA.
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| The length of the fatty acid dictates where it is activated to CoA
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| Short- and medium-chain fatty acids (Table 14.1) can cross the mitochondrial membrane by passive diffusion, and are activated to their CoA derivative within the mitochondrion. Very-long-chain fatty acids from the diet are shortened to long-chain fatty acids in peroxisomes. Long-chain fatty acids (16 ± 4 carbons) are the major components of storage triglycerides and dietary fats. They are activated to their CoA derivatives in the cytoplasm and are transported into the mitochondrion via the carnitine shuttle.
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