Topic overview

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Most fatty-acid beta oxidation takes place in the mitochondrial matrix, while very-long-chain fatty acids are first shortened in peroxisomes. Before oxidation, fatty acids are activated at the cost of two ATP equivalents. Long-chain fatty acids use the carnitine shuttle to enter the mitochondrial matrix; CPT-I is inhibited by malonyl-CoA, linking fatty-acid synthesis with oxidation. Each cycle uses dehydrogenation, hydration, dehydrogenation, and thiolysis, shortening the chain by two carbons and yielding acetyl-CoA, NADH, and FADH₂. Odd-chain and unsaturated fatty acids require additional processing steps. The pathway’s regulation and clinical relevance include fasting-related changes, ketone-body production, and disorders such as MCAD deficiency or carnitine-shuttle defects.