Low Density Lipoprotein

Low density lipoprotein ( LDL, German: low density lipoprotein ) denotes a representative of several classes of lipoproteins. It serves as a transport vehicle for the water-insoluble in the blood plasma ( lipophilic ) compounds such as cholesterol, cholesterol esters, triglycerides, fatty acids and phospholipids as well as the fat soluble vitamins, vitamin E and vitamin A.

Function

LDL transports cholesterol by the body formed by the liver to the tissues, and circulates in the blood for approximately five days. Cholesterol is required primarily as a component of cell membranes and a precursor of steroid hormones and bile acids.

Human LDL has a density of 1.019 to 1.062 g / ml and a size of 18 to 25 nm consists of an apolipoprotein B100 ( apo B100) with a molecular mass of 550 kDa ( 4536 amino acid units ), cholesterol esters, free cholesterol and phospholipids. The lipid content is approximately 80%, that is, LDL has a molar mass of about 2.7 MDa. There are many mutations of human apoB -100 known, some of which are associated with high cholesterol levels.

Furthermore, subgroups of LDL known to differ in their triglyceride content. LDL pattern A stands for the " normal" ( conventional form) of LDL. Besides them, there are also the "small, dense LDL" ( LDL pattern B ), which have a reduced triglyceride and cholesterol content, and which pose an increased risk for coronary heart disease.

Role in disease

Speak different epidemiological studies for a causal relationship between elevated cholesterol levels or LDL cholesterol in the blood and the development of atherosclerosis or coronary heart disease. Even in the development of Alzheimer's disease elevated cholesterol plays a role. Because LDL transports the greatest cholesterol fractions in blood and transport to the cells leads up, it is often and controversially as the " evil ( or bad ) cholesterol" (as opposed to "good cholesterol", the High Density Lipoprotein (HDL ) ) referred.

LDL is easily oxidized such as by pro- oxidative metal cations, and then is oxidized LDL, which are consumed on the one hand by the oxidation process, fat-soluble vitamins, especially vitamin E, and on the other hand some of the tryptophan moieties of apoB -100 are oxidized. Oxidized LDL is uninhibited and independent of the concentration added to the arterial wall by macrophages ( phagocytosis ) and stored. These fat overloading of the macrophages leads to the formation of foam cells, which is considered in medical research as one of the causes for the development of atherosclerosis.

Reduction

For the reduction of LDL cholesterol in the blood are in the human body two mutually exclusive ways. The LDL receptor pathway and the so-called scavenger pathway. The largest part, about 65% of the LDL cholesterol in plasma is metabolised by LDL receptors, wherein a region between the amino acid units 3359-3369 was identified on apoB -100 as a receptor binding site and the binding of LDL to the receptor is responsible. LDL receptors are found in all cell types of the arteries and in hepatocytes (liver cells). LDL particles are taken up by the receptors through clathrin -coated pits at the cell, where the endocytic vesicles fuse with lysosomes. By the prevailing acidic pH of the LDL receptor, which is then transported back to the cell membrane dissolves, and is degraded by lysosomal proteases. The transported lipids are transported into the cytosol and stored as lipid droplets.

Laboratory measurements ( diagnostics)

When blood tests is between the cholesterol level ( total cholesterol also, here the total cholesterol in the blood is detected ) and the LDL - cholesterol (here only the LDL fraction is determined ) distinguished. The LDL - cholesterol is not determined today in routine laboratories directly, but calculated from the directly measured values ​​of total cholesterol, triglycerides and HDL. The formula for this calculation is according to Friedewald LDL cholesterol = total cholesterol - (HDL [ triglycerides / 5] ). In Germany, the reference value range for LDL cholesterol for men and women is between 70 and 180 mg / dl.

For research purposes, the LDL is mostly isolated by ultracentrifugation from the blood plasma and is highly visible because of its yellow color, which comes from the carotenoid content, as a band in the density gradient. The LDL is highly sensitive to oxidation after isolation and can only be stored free of oxygen in a closed vessel ( by displacement of air with argon) for several days at 4 ° C.

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