Fatty acids are a major energy source and a key component of cellular membranes. Their metabolism involves two opposing pathways: beta-oxidation, which breaks them down for energy, and lipogenesis, which builds them for storage.

Fatty Acid Oxidation (Beta-Oxidation)

Activation

Fatty acids are activated in the cytoplasm by attachment to coenzyme A, forming fatty acyl-CoA. This reaction consumes ATP. The fatty acyl-CoA is then transported into the mitochondria via the carnitine shuttle.

The Beta-Oxidation Cycle

Inside the mitochondrial matrix, fatty acyl-CoA undergoes repeated cycles of four reactions: oxidation by acyl-CoA dehydrogenase (producing FADH2), hydration by enoyl-CoA hydratase, oxidation by beta-hydroxyacyl-CoA dehydrogenase (producing NADH), and thiolysis by thiolase (producing acetyl-CoA and a shortened fatty acyl-CoA).

Energy Yield

Each cycle removes two carbon atoms as acetyl-CoA. A 16-carbon palmitate molecule undergoes seven cycles, producing 8 acetyl-CoA, 7 FADH2, and 7 NADH. The acetyl-CoA then enters the citric acid cycle for further energy production.

Fatty Acid Synthesis (Lipogenesis)

Citrate Shuttle

When energy is abundant, excess acetyl-CoA in the mitochondria is exported to the cytoplasm via the citrate shuttle. Citrate is cleaved by ATP-citrate lyase to produce acetyl-CoA and oxaloacetate.

Malonyl-CoA Formation

Acetyl-CoA carboxylase converts acetyl-CoA to malonyl-CoA, the committed step of fatty acid synthesis. This enzyme is activated by insulin and citrate and inhibited by palmitoyl-CoA.

Elongation Cycle

Fatty acid synthase, a large multifunctional enzyme, carries out a repeated cycle of condensation, reduction, dehydration, and reduction. Each cycle adds two carbon atoms. The process requires NADPH and produces palmitate (16:0) as the primary product.

Regulation

Fatty acid oxidation and synthesis are reciprocally regulated. When energy is low, AMPK activates oxidation and inhibits synthesis. When energy is abundant, insulin activates synthesis and inhibits oxidation.