Lipoprotein lipase (LPL) belongs to the lipases and plays a crucial role in lipid metabolism. It is responsible for the breakdown of triglycerides in chylomicrons and very low density lipoproteins (VLDL) into fatty acids and monoacylglycerol. The released fatty acids are used for energy production or to build body fat.
What is lipoprotein lipase?
Lipoprotein lipase (LPL) is an enzyme that belongs to the lipases. Lipases are responsible for the breakdown of triglycerides (triacylglycerols) into fatty acids and glycerol. Triglycerides represent esters of the triple alcohol glycerol with three fatty acids each. They are known as fats or fatty oils. Dietary fats are ingested with food and are first broken down in the intestine by extracellular lipases from the pancreas. However, some triglycerides enter the bloodstream via the serum as a result of absorption in the small intestine, where they are bound to lipoproteins that guarantee their transportability in the blood. Lipoprotein lipase is now the enzyme that breaks down the triglycerides bound to the lipoproteins into fatty acids and monoacylglycerol. It consists of 448 amino acids and depends on the coenzyme apolipoprotein C2 for its function. Lipoprotein lipase represents a water-soluble enzyme that is bound to the endothelial cells of blood vessels via certain glycoproteins (proteoglycans). It is produced in the liver. The enzyme catalyzes the hydrolysis of triglycerides to two fatty acid molecules and one monoacylglycerol molecule each. The apolipoproteins are the carrier molecules of the triglycerols and mediate their transportability in the aqueous environment. Apolipoprotein C2 also acts as a receptor for lipoprotein lipase, activating the hydrolysis of triglycerides.
Function, effects, and roles
The function of lipoprotein lipase is to catalyze the breakdown of fats absorbed by intestinal cells completely in the blood. First, dietary fats are degraded by pancreatic lipases in the small intestine to fatty acids and glycerol. Further triglycerides enter the blood through absorption via the small intestine, where they bind to lipoproteins to form a lipid-protein complex. Chylomicrons are formed in the process. They represent lipoprotein particles with a diameter of 0.5 to 1 micrometer. Their density is below 1000 g/ml. The lipid core contains mainly triglycerides with a small admixture of cholesterol esters. The cholesterol-containing shell of the chylomicrons contains phospholipids as a structural element. The apolipoproteins, to which the triglycerides are bound, are now also incorporated into this shell. The chylomicrons contain 90 percent triglycerides. They enter the bloodstream from the small intestine via the lymphatic system. Particularly in the capillaries of the muscle and adipose tissue, the triglycerides are degraded to fatty acids and glycerol with the help of the LPL. The fatty acids are either used immediately in muscle tissue for energy production or in adipose tissue to build up the body’s own triglycerides as storage fat. After about ten hours of abstinence from food, chylomicrons are no longer detectable in the blood, as the triglycerides have then been completely broken down. Other components of the blood are the so-called VLDL (very low density lipoprotein). These structural units are secreted by the liver and contain triglycerides, phospholipids and cholesterol. The VLDL transport these components via the bloodstream from the liver to the individual organs. Along this pathway, in turn, the triglycerides are broken down by lipoprotein lipase and the released fatty acids are taken up by the body’s cells. The decrease in triglycerides converts the VLDL into LDL (low density lipoprotein). LDL mainly contain phospholipids, cholesterol esters, and lipoproteins
Formation, occurrence, properties, and optimal levels
Lipoprotein lipase is synthesized in the liver. It represents another extracellular lipase in addition to the pancreatic lipases. LPL is located on the outside of the membranes of endothelial cells of a wide variety of organs, including fat cells. There it is connected to the cell membranes via so-called proteoglycans. However, it is of particular importance for the endothelial cells of the blood vessels, since here it can directly control the hydrolysis of the triglycerides found in the chylomicrons and VLDLs. Heparin is injected to measure lipoprotease activity.Heparin ensures the loosening of the binding of lipoprotein lipases from the proteoglycans, so that after a heparin injection there is an increased concentration of free lipoprotein lipases, which can thus be determined by their activity. Among other things, a deficiency of lipoprotein lipase can be detected by this assay.
Diseases and disorders
Deficiency of lipoprotein lipase often leads to severe health problems. If too little lipoprotein lipase is present or if its activity is inadequate because of a genetic defect, the triglycerides found in chylomicrons and VLDLs may be poorly broken down or not broken down at all. Lipoprotein lipase deficiency can be both primary genetic and secondary to chemotherapy, for example. A primary deficiency of LPL is rare and is caused by an autosomal recessive genetic defect. In this case, a so-called chylomicronemia develops, which is characterized by a milky-framed serum and is referred to as type I hyperlipidemia. The triglycerides in the chylomicrons are no longer broken down. As a result, severe pancreatitis with milk intolerance and abdominal pain occur repeatedly. In addition, bursting xanthomas and hepatomegaly constantly develop. The only treatment is a low-fat diet and abstinence from alcohol. The cause of this disease is often mutations of the LPL gene on chromosome 8 or the APOC2 gene. The secondary form of type I hyperlipidemia usually occurs with chemotherapy and is transient in nature.
