Lipogenes

Lipogenes, or lipogenesis, is the metabolic process by which fatty acids and other lipids are synthesized from smaller precursors, primarily acetyl-CoA generated from carbohydrate metabolism. In humans, the liver is the principal site of de novo lipogenesis, with adipose tissue also capable of synthesizing and storing triglycerides.

The core pathway is cytosolic. Acetyl-CoA is first carboxylated to malonyl-CoA by acetyl-CoA carboxylase (ACC), the committed step of fatty acid synthesis. Malonyl-CoA serves as a substrate for the fatty acid synthase (FAS) complex, which elongates the growing acyl chain through iterative cycles to produce palmitate (16:0). Reducing equivalents in the form of NADPH, supplied mainly by the pentose phosphate pathway and by other enzymes, drive the reductive steps. The cytosolic acetyl-CoA mainly derives from citrate exported from mitochondria and cleaved by ATP-citrate lyase to regenerate acetyl-CoA and oxaloacetate.

The synthesized fatty acids can be elongated, desaturated, and esterified with glycerol-3-phosphate to form triglycerides, which are stored in adipose tissue or packaged into very low-density lipoproteins for export. Regulation is tightly controlled: lipogenesis is stimulated by insulin and high carbohydrate intake, while glucagon and epinephrine suppress it. Malonyl-CoA also inhibits mitochondrial fatty acid entry by inhibiting carnitine palmitoyltransferase I, reducing fatty acid oxidation.

Clinical relevance and variation exist. In humans, dysregulated lipogenesis is associated with metabolic conditions such as non-alcoholic fatty liver disease and obesity. In plants and other organisms, lipid synthesis can occur in different cellular compartments but follows a conserved set of biochemical principles.