Cholesterin, also cholesterol (from Greek χολή cholé, German ‘bile’, and from στερεός stereós, German ‘solid, hard, hardened’), is a fatty natural substance occurring in all animal cells. The substance was found in crystalline form in gallstones in the 18th century, which is why the French chemist Eugène Chevreul, founder of oleochemistry, coined the name “cholestérine” in 1824. The substance is produced in the liver of animals and, in addition to bile, is found in blood and tissues, particularly in nervous tissue. Cholesterol influences the stabilization of cell membranes, nerve function, the production of sex hormones and other processes.
Small amounts of cholesterol are also found in plant cells (potato tops, pollen, isolated chloroplasts) and in bacteria.[3] Vegetable oils that are particularly high in cholesterol are corn oil (55 mg per kg), rapeseed oil (53 mg per kg) and cottonseed oil (45 mg per kg). Typical animal sources of cholesterol contain many times this amount.[4] For example, a typical value for butter is 2340 mg per kg.[5]
An intermediate product of cholesterol biosynthesis, 7-dehydrocholesterol, is the provitamin for the formation of vitamin D through UV light.
High levels of LDL cholesterol in the blood increase the risk of heart attack and stroke.[6][7] In Austria, about 8.2% of premature deaths are due to elevated LDL cholesterol levels.[8][9]
Cholesterol is a vital sterol and an important component of the cell membrane. It increases the stability of the membrane and, together with proteins, helps to transport signal substances into and out of the cell membrane.
The human body contains around 140g of cholesterol, over 95% of cholesterol is found within cells and cell membranes. In order to be able to supply the cells with cholesterol, which is lipophilic (fat-soluble) and hydrophobic (water-repellent when wetted), it is bound to lipoproteins for transport. These can be of different densities and are classified according to their behavior during
Centrifugation or electrophoresis divided into chylomicrons, VLDL, IDL, LDL, HDL and lipoprotein a.
Cholesterol is used in the body, among other things, as a precursor to steroid hormones and bile acids. For the formation of hormones, the cholesterol side chain severing enzyme converts cholesterol to pregnenolone. This is the starting compound from which the body builds the sex hormones testosterone, estradiol and progesterone and adrenal hormones (corticoids) such as cortisol and aldosterone. Bile acids such as cholic acid and glycocholic acid are also based on the starting substance cholesterol.[10]
Cholesterol is excreted by the liver by being secreted into the intestines in the form of bile acids via the bile ducts (about 500 mg per day). Bile acids are required for the absorption of water-insoluble food components, including cholesterol.
Cholesterol is emulsified by bile acids and absorbed in the small intestine. Since about 90% of the bile acids are reabsorbed, the elimination of cholesterol is correspondingly ineffective. Drugs such as cholestyramine, which bind bile acids and thus make them more difficult to absorb, can increase cholesterol excretion. However, the lowering of the cholesterol level is then compensated for by an increase in the LDL receptor density on liver cells and the associated increased uptake of cholesterol from the blood into the liver, partly also by increased new synthesis.[15]
New research also shows that the body uses cholesterol to biosynthesize cardioactive glycosides. The importance of these endogenously synthesized glycosides is still largely unknown.
Based on sediment finds with chemical cholesterol relatives (sterols), some researchers assume that the cholesterol molecule must be very old in terms of evolutionary history, provided that it has never appeared in anything other than living matter.[11]
However, the biosynthesis of the molecule can only function since oxygen has been present in the atmosphere. For this reason, hardly any cholesterol is found in bacteria and the membranes of mitochondria; Plants and fungi also contain no cholesterol, but they do contain other, structurally similar sterols.
Cholesterol is a polycyclic alcohol. As a steroid belonging to the group of sterols (sterols), it is traditionally counted among the lipid-like substances; contrary to popular misconception, however, it is not fat. The steroids belong to the isoprenoids which, in contrast to the fats, are not esters of fatty acid and alcohol, but can have hydrophilic poles as various patterns in their hydrophobic basic structure.
Further reading…
Cholesterin
Cholesterol
Cholesterol, like many substances, is sensitive to oxidants. Auto-oxidation processes can lead to many reaction products. So far, more than eighty such substances are known, which often have considerable physiological effects. The oxidation products can be isolated and purified by chromatographic methods. Your secure identification takes place e.g. B. by spectroscopic or spectrometric methods such as mass spectrometry.[12] A comprehensive description of these cholesterol oxidation products is given in the work by Leland L. Smith: Cholesterol Autoxidation.[13]
Cholesterol is an essential zoostone for humans and animals. Most (90%) of cholesterol in humans is made (synthesized) in the body itself, in adults the amount is 1 to 2 g per day, and only a small amount can be obtained from food. Cholesterol absorption is on average 0.1 to 0.3 g per day and can be increased to a maximum of 0.5 g per day.
All animals synthesize cholesterol. Starting with “activated acetic acid”, acetyl-CoA, isopentenyl diphosphate is produced in four steps via mevalonic acid. A further three reaction steps lead to squalene. After ring closure to form lanosterol, about a dozen enzymatic reactions follow, which can also run in parallel, until finally cholesterol is formed. The details of this last segment are not known, but the enzymes involved have been identified.[14]
Cholesterol is excreted by the liver by being secreted into the intestines in the form of bile acids via the bile ducts (about 500 mg per day). Bile acids are required for the absorption of water-insoluble food components, including cholesterol.
Cholesterol is emulsified by bile acids and absorbed in the small intestine. Since about 90% of the bile acids are reabsorbed, the elimination of cholesterol is correspondingly ineffective. Drugs such as cholestyramine, which bind bile acids and thus make them more difficult to absorb, can increase cholesterol excretion. However, the lowering of the cholesterol level is then compensated for by an increase in the LDL receptor density on liver cells and the associated increased uptake of cholesterol from the blood into the liver, partly also by increased new synthesis.[15]
Further reading…
Cholesterol
High cholesterol
Cholesterol is taken up by many animal cells via receptor-mediated endocytosis. It is transported in the blood mainly as cholesterol esters in the form of lipid-protein particles, the low-density lipoproteins (LDL). When a cell needs LDL, it makes LDL receptors on its cell membrane. These associate with clathrin-coated pits to which an endocytic signal on the cytoplasmic portion of the LDL receptor binds. An adapter protein, AP2, is bound there, which attracts clathrin to initiate endocytosis. After the LDL particles are taken up, they go to the early endosomes.
For this, the clathrin with which they were coated is previously removed from the vesicles. In the early endosomes, the pH is low (acidic), causing the LDL to detach from the receptor and enter a late endosome, which takes it to the lysosomes. These hydrolyze the cholesterol esters to free cholesterol.[16]
The biosynthesis of cholesterol, which was explained in particular by the work of Konrad Bloch, Feodor Lynen, George Joseph Popják and John W. Cornforth, starts from the end products of the mevalonate biosynthesis pathway, from dimethylallyl pyrophosphate and isopentenyl pyrophosphate, and requires 13 further reactions. In humans, the liver and intestinal mucosa are the main sites of cholesterol synthesis.
The balance between required, self-produced and dietary cholesterol is maintained through a variety of mechanisms. The inhibition of HMG-CoA reductase, the most important enzyme in cholesterol biosynthesis, by cholesterol can be considered important (HMG-CoA reductase is inhibited even more strongly by lanosterol, a precursor of cholesterol).
Products of this metabolic pathway (cholesterol synthesis) thus inhibit “their” enzyme; this is a typical example of negative feedback. In addition, the half-life of HMG-CoA reductase is greatly reduced with increased lanosterol levels, since it then binds more to the proteins Insig-1 and Insig-2, which ultimately leads to their degradation in the proteasome.[17]
There are many other less direct regulatory mechanisms that operate at the transcriptional level. Important here are the proteins SCAP, Insig-1 and Insig-2, which in the presence of cholesterol, for which they have a binding site, regulate the activity of a large number of genes via the proteolytic activation of SREBPs. Insulin also plays a role here, since it e.g. increases transcription of SREBP1c.
HMG-CoA reductase, the key enzyme in cholesterol biosynthesis, can be specifically and effectively inhibited by various substances (e.g. statins, which represent a specific class of drugs as HMG-CoA reductase inhibitors). Uptake into the cell is activated via the LDL receptor.