Low density lipoprotein
Low-density lipoprotein ( LDL , German: lipoprotein low density ) describes representatives of one of several classes of lipoproteins . It serves as transport vesicles to the plasma water ( lipophilic ) substances such as cholesterol , Cholesterinester , triglycerides , fatty acids and phospholipids as well as the fat-soluble vitamins Vitamin E and Vitamin A .
function
LDL transports the cholesterol produced by the body itself from the liver to the tissues and circulates in the blood for about five days. Cholesterol is mainly required as a component of cell membranes and as a precursor to bile acids and steroid hormones .
Human LDL has a density of 1.019 to 1.062 g / ml and a size of 18 to 25 nm . It consists of an apolipoprotein B100 (Apo B100) with a molar mass of 550 kDa (4536 amino acid units), cholesterol esters, free cholesterol and phospholipids. The lipid content is around 80%, which means that LDL has a molar mass of around 2.7 MDa . Numerous mutations of ApoB-100 in humans are known, some of which are associated with high cholesterol.
Furthermore, subgroups of LDL are known that differ in their triglyceride content . The LDL pattern A denotes the “normal” (usual form) LDL. In addition to them, however, there is also the “small, dense LDL” (LDL pattern B, also sdLDL or s-LDL), which have a reduced triglyceride and cholesterol content and which pose an increased risk of coronary heart disease .
In addition to extrinsic factors that determine the level of the LDL level in the blood, the activity of the enzyme proprotein convertase subtilisin / kexin type 9 ( PCSK9 ) is an important determining factor because it binds the LDL receptor and the complex is broken down in the liver thus less LDL is absorbed from the blood. A rare gene variant with decreased PCSK9 activity is associated with lower LDL levels and less common coronary heart disease . This led to the development of specific monoclonal antibodies directed against PCSKA9 .
Role in disease
Various epidemiological studies suggest a causal connection between increased cholesterol levels or LDL cholesterol in the blood and the development of arteriosclerosis or coronary heart disease. Elevated cholesterol levels also play a role in the development of Alzheimer's disease . Because LDL transports the largest proportion of cholesterol in the blood and transports it to the cells, it is often and controversially referred to as "bad (or bad) cholesterol" (as opposed to "good cholesterol", high density lipoprotein (HDL)) designated.
LDL can be easily oxidized by pro-oxidative metal cations, for example, and then forms oxidized LDL, whereby on the one hand fat-soluble vitamins, especially vitamin E, are consumed by the oxidation process and, on the other hand, some tryptophan units are oxidized by apoB-100. Oxidized LDL is absorbed ( phagocytosed ) and stored in the arterial walls by macrophages uninhibited and independent of the concentration . This fat overload of the macrophages leads to the formation of foam cells , which medical research regards as one of the causes of the development of arteriosclerosis .
Dismantling
There are two independent pathways in the human body for breaking down LDL cholesterol in the blood: the LDL receptor pathway and the so-called scavenger pathway . The largest part, about 65% of the LDL cholesterol in the plasma, is metabolized via LDL receptors , whereby a region between the amino acid units 3359 to 3369 on the apoB-100 has been identified as a receptor binding site and for the binding of LDL to the receptor responsible for. LDL receptors are found in all cell types of the arteries and in hepatocytes (liver cells). The LDL particles are absorbed into the cells by the receptors via clathrin-coated pits , where the endocytotic vesicles fuse with lysosomes . Due to the acidic pH prevailing there, the LDL is released from the receptor, which is then transported back to the cell membrane , and is broken down by lysosomal proteases . The transported lipids are transported into the cytosol and stored as lipid droplets.
Laboratory measurements (diagnostics)
In blood tests, a distinction is made between the cholesterol value (also total cholesterol , here the total cholesterol in the blood is recorded) and the LDL cholesterol (here only the LDL proportion is determined). Today, LDL cholesterol is measured directly in routine laboratories using clinical chemistry analyzers. (Roche, Beckmann, Siemens etc.) A calculation using the Friedewald formula using the directly measured values of total cholesterol, triglycerides and HDL is only rarely done. The formula for this calculation according to Friedewald is LDL cholesterol = total cholesterol - (HDL + [triglycerides / 5]) . In Germany, the reference value range for LDL cholesterol for women and men is between 70 and 180 mg / dl.
For research purposes, the LDL is mostly isolated from the blood plasma by ultracentrifugation and is clearly visible as a band in the density gradient solution because of its yellow color, which comes from the carotenoid content . After isolation, the LDL is very sensitive to oxidation and can only be stored oxygen-free in a closed vessel (by displacing air with argon ) for a few days at 4 ° C.
See also
Individual evidence
- ↑ A. Yamamoto: Mechanism of the production of small, dense Ldl in hypertriglyceridemia: role of cholesteryl ester transfer protein and hepatic triglyceride lipase. (No longer available online.) In: ingentaconnect.com. Formerly in the original ; Retrieved March 27, 2010 . ( Page no longer available , search in web archives )
- ^ Neil J. Stone, Donald M. Lloyd-Jones: Lowering LDL Cholesterol is good, but how and in whom? New England Journal of Medicine 2015, Volume 372, Issue 16, April 16, 2015, Pages 1564-1565, DOI: 10.1056 / NEJMe1502192
- ↑ A. Giessauf, E. Steiner, H. Esterbauer "Early destruction of tryptophan residues of apolipoprotein B is a vitamin E-independent process during copper-mediated oxidation of LDL" BBA Vol. 1256 (1995) 221-232.