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Mitochondria can utilize carbohydrate, protein, or fat as a source of energy. Pyruvate, derived from glucose or amino acids, is transported through the mitochondrial inner membrane using a specific transporter,1 decarboxylated to acetyl-coenzyme A (CoA), and enters the citric acid cycle producing reducing equivalents in the form of 1,5-dihydroflavin adenine dinucleotide (FADH2) and nicotinamide adenine dinucleotide (NADH). These reducing equivalents are transported down the electron transport chain of inner mitochondrial membrane complexes, ultimately generating adenosine triphosphate (ATP) and consuming oxygen. Similarly, activated fatty acids (acyl-CoAs) entering the fatty acid β-oxidation (FAO) spiral generate reducing equivalents in the form of NADH and FADH2, which also pass down the oxidative phosphorylation respiratory chain complexes to generate ATP.
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Mitochondrial FAO represents a normal physiologic response to increased energy demands during periods of reduced caloric intake associated with fasting, reduced intake due to gastrointestinal disease, febrile illness, and increased muscular exertion. The normal endocrine response to increased energy demand results in mobilization of lipid stores and generation of free fatty acids at the plasma membrane. Long-chain fatty acids (longer than C12) and carnitine are transported by specific plasma membrane transporters such as fatty acid transporter (FAT) and fatty acid–binding protein (FABP), respectively. No specific proteins have been implicated in the movement of free fatty acids across the cytoplasm to mitochondria. The carnitine transporter (OCNT2) is required to maintain intracellular carnitine stores, necessary for transport of long chain fats into mitochondria. Short- and medium-chain fatty acids (shorter than C12) are transported directly into the cytosol (Figures 9-1, 9-2, 9-3).
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