Low density lipoproteins form one of several lipoprotein classes that are able to take up cholesterol and other water-insoluble lipophilic substances and transport them in the blood serum. LDLs perform the task of taking up cholesterol at its point of origin – predominantly the liver – and delivering it to target tissues. In contrast, high-density lipoproteins have the task of absorbing excess cholesterol in the tissues and transporting it back to the liver for further utilization.
What are low density lipoproteins?
Low density lipoproteins (LDL) are composed of about half transport proteins and half cholesterol, cholesterol esters, triglycerides, and phospholipids. The protein portion is composed mainly of apolipoproteins, also called apoproteins, which are also synthesized by the liver and intestinal epithelium of the small intestine. The apoproteins each have a hydrophilic group that, together with the phospholipids, ensure that LDLs, like the other lipoprotein classes, can be dissolved in serum to perform their transport function. The class of LDLs includes lipoproteins with a density of 1.019 to 1.062 g/ml. The molecules with a diameter of 18 to 25 nanometers reach a molar mass of 550 kDa. The main function of LDL is to absorb cholesterol produced by the body itself in the liver or in the intestinal mucosa at the site of formation and transport it to the target tissue. An abnormally high concentration of LDLs in the serum accompanied by a low concentration of HDLs is considered a health concern. In these cases, it is believed that too much cholesterol is stored in the vessel walls because there are too few opportunities for removal.
Function, effect, and tasks
Cholesterol performs a variety of important functions in the body. It is a component of all cell membranes and ensures that they function properly. This also applies to vascular epithelia, whose cell membranes must withstand special demands. In addition, cholesterol makes important contributions to fat metabolism and is a starting material for the synthesis of bile acids and vitamin D, as well as for the production of some steroid hormones such as estrogen, testosterone and the stress hormone cortisol. Many brain functions also depend on an adequate supply of cholesterol. For example, decreased brain cholesterol correlates with decreased cognitive and other performance. For decades, high cholesterol levels in blood plasma were judged to be fundamentally harmful because atherosclerotic changes in blood vessels caused by so-called plaques contain cholesterol. The plaques are formed due to excessive storage of cholesterol and actually serve to repair tiny hairline fractures and other damage in the membranes of the vascular epithelia. Since cholesterol itself cannot be measured, but only the concentration of lipoproteins, LDLs in particular have been under general suspicion as the cause of atherosclerotic changes in blood vessels. In their function as transport proteins, their task is to absorb cholesterol at its point of origin in the liver or, to a lesser extent, in the intestinal mucosa of the small intestine, to carry it to the target tissue and to release it there. This is also true in the case of initiated repair mechanisms in the vessels. Normally, excess cholesterol is taken up by HDLs in the target tissue, carried back to the liver, and further metabolized, ie, degraded or recycled, in the liver.
Formation, occurrence, properties, and optimal levels
The concentration of the individual lipoprotein fractions in serum is largely dependent on a genetic component and on lifestyle habits regarding exercise intensity. The influence of diet is only weakly pronounced because by far the largest proportion of lipoproteins does not come directly from food but is synthesized by the body itself from simple basic building blocks mainly in the liver and in the intestinal mucosa of the small intestine. The so-called mevalonate pathway plays a role in biosynthesis. The mevalonate pathway produces DMAPP (dimethylallyl pyrophosphate), which is the starting substance for the synthesis of lipoproteins. From DMAPP, LDL and also the other lipoprotein fractions are formed in an 18-step reaction chain.In recent years, the assumptions about health risks with regard to cholesterol levels have shifted significantly – starting from the USA. Whereas in the past a high LDL level per se was considered a health risk, the focus is now on the ratio of LDL to HDL. A ratio above four is considered a clear risk factor for the occurrence of atherosclerotic vascular changes, CHD, heart attack and stroke. Also independent of the LDL level, a concentration of HDL above 60 mg/dl is considered favorable, whereas an HDL level below 40 mg/dl is considered fundamentally risky. A serum LDL concentration of 70 to 180 mg/dl is considered the reference range for women and men alike in Germany.
Diseases and disorders
The main hazards associated with low-density lipoproteins lie in serum concentrations that are too low or too high, although the risks cannot be derived from the concentration of LDL alone but must be seen in relation to HDL levels and in relation to lipoprotein, which has a very similar structure to LDL and appears to have substantial influence on the formation of plaques in the vessels. Homozygous familial hypercholesterolemia (HoHF), which occurs very rarely with approximately one case per million population, manifests itself in Ldl concentrations that can reach 600 to 1,000 mg/dl. The genetically determined metabolic disease already manifests itself in childhood and leads to visible fatty nodules in the skin and to early-onset arteriosclerosis with all its sequelae. Heterozygous familial hypercholesterolemia (HeHF), on the other hand, has a much milder course, but is relatively common, with one case per 500 inhabitants. Symptoms are caused by a genetic disorder of LDL receptors.
