Fatty Acid Metabolism and Regulation Mechanisms

Fatty acid metabolism encompasses the coordinated enzymatic pathways that synthesise, transport and degrade long-chain carboxylic acids critical for cellular function and energy homeostasis. In de novo lipogenesis, acetyl-coenzyme A (acetyl-CoA) is carboxylated to malonyl-CoA by acetyl-CoA carboxylase, and successive condensations via fatty acid synthase generate saturated carbon chains. Subsequent elongation and desaturation introduce additional carbons and double bonds to yield diverse fatty acids. Fatty acid mobilisation involves release from glycerolipids and transport into mitochondria via the carnitine shuttle for β-oxidation, producing acetyl-CoA, NADH and FADH₂. A complementary peroxisomal pathway handles very-long-chain species. Regulation occurs through allosteric effectors such as citrate and long-chain acyl-CoA, covalent phosphorylation by kinases (notably AMP-activated protein kinase) and transcriptional control by sterol regulatory element-binding proteins and nuclear receptors. Hormonal cues, particularly insulin and glucagon, integrate systemic energy demands. Dysregulation contributes to metabolic syndrome, steatosis and cancer, underscoring the importance of elucidating regulatory nodes for therapeutic targeting.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Fatty Acid Metabolism and Regulation Mechanisms publication trend

The graph below shows the total number of articles in fatty acid metabolism and regulation mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Acetyl-CoA carboxylase (ACC): A biotin-dependent enzyme that catalyses the ATP-driven carboxylation of acetyl-CoA to malonyl-CoA, serving as the rate-limiting step in fatty acid biosynthesis.

β-Oxidation: A mitochondrial and peroxisomal pathway that sequentially removes two-carbon units from fatty acyl-CoA molecules, producing acetyl-CoA for energy generation.

De novo lipogenesis (DNL): The metabolic process by which carbohydrates and other precursors are converted into fatty acids within the cytosol.

Sterol regulatory element-binding proteins (SREBPs): Transcription factors that regulate genes involved in cholesterol and fatty acid synthesis in response to cellular lipid status.

AMP-activated protein kinase (AMPK): A cellular energy sensor that phosphorylates ACC and other targets to inhibit anabolic processes when energy levels are low.

References

1. Palmitate. Trends in Endocrinology and Metabolism (2025).
2. The amount of membrane cholesterol required for robust cell adhesion and proliferation in serum-free condition. PLOS ONE (2022).
3. Regulation of Hepatic Acetyl Coenzyme A Carboxylase by Phosphorylation and Dephosphorylation. Journal of Biological Chemistry (1973).
4. Regulation of the Activity of Acetyl Coenzyme A Carboxylase by Palmitoyl Coenzyme A and Citrate. Journal of Biological Chemistry (1972).