Lipogenesis

Lipogenesis is the process by which simple sugars such as glucose are converted to fatty acids, which are subsequently esterified with glycerol to form the triacylglycerols that are packaged in VLDL and secreted from the liver.occurs in the cytosol of cells. Lipogenesis encompasses the processes of fatty acid synthesis and subsequent triglyceride synthesis.Lipogenesis starts with acetyl-CoA and builds up by the addition of two carbons units. The synthesis occurs in the cytoplasm in contrast to the degradation (oxidation) which occurs in the mitochondria. Many of the enzymes for the fatty acid synthesis are organized into a multienzyme complex called fatty acid synthetase . Insulin is an indicator of the blood sugar level of the body, as its concentration increases proportionally with blood sugar levels. Thus a large insulin level is associated with the fed state. As one might expect therefore, it increases the rate of storage pathways, such as lipogenesis. Insulin stimulates lipogenesis in three main ways.

Malonyl-coenzyme A In fat synthesis, the enzyme pyruvate dehydrogenase, which forms acetyl-coA, and also acetyl CoA carboxylase which forms malonyl-coA are obvious control points. These are activated by insulin. This leads to an overall increase in the levels of malonyl-coenzyme A, which is the substrate required for fat synthesis. Thus, the flux down storage pathway is increased when there is sufficient glucose in the 'fed' state.

Pyruvate dehydrogenase dephosphorylation Pyruvate dehyrdrogenase dephosphorylation is increased with the release of insulin. The dephosphorylated form is more active.This mechanism is not clear, as insulin binds to extra-cellular parts of protein receptors and pyruvate dehydrogenase is found in the mitochondrial matrix. There must be some sort of secondary messenger process. This mechanism leads to the increased rate of catalysis of this enzyme, so increases the levels of acetyl-coA.