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Beta-Oxidation of Fatty Acids
Long-chain fatty acids enter mitochondria and shed two carbons per cycle as acetyl-CoA, yielding 7 FADH2, 7 NADH, and 8 acetyl-CoA from one palmitate.
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Beta-Oxidation of Fatty Acids
Beta-oxidation is the mitochondrial process of breaking fatty acids into two-carbon acetyl-CoA units for entry into the TCA cycle. Each cycle of beta-oxidation removes two carbons and produces one FADH2 (feeds Complex II of ETC) and one NADH (feeds Complex I). A 16-carbon palmitate therefore requires 7 cycles, producing 7 FADH2, 7 NADH, and 8 acetyl-CoA. This makes fat a far denser energy store than carbohydrate: palmitate yields about 106 ATP equivalents versus 32 ATP from one glucose molecule.
Fatty acids enter the mitochondria via the carnitine shuttle (CPT1/CPT2), which is the rate-limiting and most-regulated step. Once inside, each cycle proceeds through four enzymatic steps: acyl-CoA dehydrogenase (produces FADH2), enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase (produces NADH), and thiolase (cleaves acetyl-CoA and returns a shortened acyl-CoA to restart the cycle).
Insulin suppresses beta-oxidation by raising malonyl-CoA via ACC, which allosterically blocks CPT1. This is why fat burning only becomes substantive when insulin is low.
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This beta-oxidation of fatty acids is an editorial illustration built to represent the concept accurately. Where it shows figures, they are typical or representative values chosen to make the relationship clear, not a single underlying dataset. The diagram and its explainer are reviewed and maintained centrally, and updated over time as understanding improves.
The four-step beta-oxidation spiral
Beta-oxidation degrades fatty acids inside the mitochondrial matrix through a repeating four-reaction cycle: oxidation by acyl-CoA dehydrogenase (producing FADH2), hydration, a second oxidation (producing NADH), and thiolytic cleavage that releases one acetyl-CoA. Each turn of the spiral removes two carbons from the carboxyl end of the chain, shortening it by an acetyl unit until the molecule is fully consumed.
Why fatty acids need a transport shuttle
Long-chain fatty acids cannot freely cross the inner mitochondrial membrane. They are first activated to acyl-CoA in the cytosol, then ferried across by the carnitine shuttle (CPT1, the carnitine-acylcarnitine translocase, and CPT2). CPT1 is the rate-limiting step and is inhibited by malonyl-CoA, linking fat breakdown to the cell's fed or fasted state.
The yield from one palmitate
Palmitate, a 16-carbon saturated fatty acid, undergoes seven cycles to produce eight acetyl-CoA, seven FADH2, and seven NADH. The acetyl-CoA enters the citric acid cycle, while FADH2 and NADH feed oxidative phosphorylation. This high ATP yield per gram is why fat is the body's densest fuel store and the dominant substrate during prolonged low-intensity activity and fasting.
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