Lipogenesis is the process involving the synthesis of fatty acids or triglycerides, which is controlled and regulated by a number of factors in the body. The process is stimulated by a diet high in carbohydrates and several hormones in the body, such as insulin, mediate the process.
Role of Insulin
Insulin is a peptide hormone that has a large impact on the body’s metabolic processes. It is released from the pancreas in response to high blood sugar levels and has many effects on the regulation of the concentration of glucose in the body. In particular, it promotes the storage of sugars in the body and stimulates lipogenesis to reduce the blood sugar levels.
It does this through the activation of two enzymatic pathways: pyruvate dehydrogenase (PDH) dephosphorylation and acetyl-CoA carboxylase (ACC) conversion. Each of these two pathways is discussed in more detail below.
Pyruvate Dehydrogenase (PDH) Dephosphorylation
When insulin is released it stimulates the activity of the PDH phosphatase enzyme, which plays an important role in the removal of the phosphate from the pyruvate dehydrogenase, through a process known as dephosphorylation. The end product of this reaction from PDH is acetyl-CoA. When the levels of acetyl-CoA are increased, the lipogenesis pathway is stimulated and more lipid molecules are synthesized.
Acetyl-CoA Carboxylase (ACC) Enzyme
In addition to its effect on PDH, insulin also stimulates the activity of the acetyl-CoA carboxylase (ACC) enzyme.
This enzyme is responsible for the conversion reaction from acetyl-CoA to malonyl-CoA. The end product allows for additional carbon atoms that are used in the formation of larger fatty acids through a process of biosynthesis.
Role of Glucagon
Glucagon can be viewed as an antagonist of insulin as it has the opposite effect and decreases the production of fatty acids through lipogenesis. It does this by increasing the process of phosphorylation, which inhibits ACC and slows the synthesis of lipids.
Therefore, glucagon also plays an important role in the physiological regulation of lipogenesis by inhibiting the process from occurring when it energy stores are immediately required.
When there is a high concentration of long chain fatty acids, they can inhibit the activity of ACC. They act as negative allosteric regulators and stop the synthesis of fatty acids, or process of lipogenesis.
ATP is a primary source of energy for the needs of human body cells, and when the ATP stores are depleted, the levels of AMP rise. As a result, AMP-activated protein kinase initiated the phosphorylation reaction of ACC and inhibits the lipogenesis process.
This pathway is beneficial due to its ability to prevent the diversion of glucose into fat storage pathways when there is a requirement for energy sources in the body.
Control and Regulation
As a result of these various physiological mechanisms, the process of lipogenesis can be carried out in a controlled manner. There are a number of hormones involved in this regulatory process, in addition to allosteric regulators and energy sources that play a role.