Cholesterol, enjoy but eat in moderation
- Cholesterol is in cell membranes, it reduces the fluidity and permeability of the membranes. Plasma membranes consist of up to 25% cholesterol. It is hardly in intracellular membranes.
- It is important for the production of adrenal cortex and sex hormones
- It is the precursor to bile acids and steroid hormones such as vitamin D
- It is a substance that can cause cardiovascular disease and damage to the blood vessels at high concentrations
- Cholesterol is an important component of bile salts
- It is a precursor to various compounds that play a role in proliferation (cell division), tumor cell growth, electron transport and oxidative stress
StructureCholesterol is made up of three Greek words: chole stands for bile, stereos means solid and the suffix -ol stands for alcohol. It is an amphipathic substance, because it has a polar -OH group and the rest of the molecule is non-polar. It is poorly soluble in water. only 30% circulates in the free form. The majority is bound to long fatty acids.
SynthesisThe liver makes its own cholesterol for the most part. This happens for the most part in the cytoplasm. The synthesis of cholesterol consists of many steps. It starts with the substance acetyl-CoA, a coenzyme of the citric acid cycle. Together with acetoacetyl-CoA, the 3-hydroxy-3-methylglutaryl-CoA forms reductase under the influence of the enzyme HMG-CoA.
This enzyme is the speed-determining enzyme in the formation of cholesterol and is inhibited by the food intake of cholesterol and stimulated by fasting.
The energy required for the synthesis of cholesterol comes mainly from ATP and acetyl-CoA, and is mainly obtained from the oxidation of fatty acids, pyruvic acid and ketogenic amino acids. HMG-CoA reductase inhibitors lower LDL cholesterol, and increase the activity of LDL receptors so that various lipoproteins are removed more quickly. Statins reduce cholesterol (linked to LDL) in patients with arteriosclerosis. It inhibits the speed-determining enzyme HMG-CoA, thereby inhibiting the production of cholesterol. Cellular cholesterol is falling. The activity of LDL receptor is stimulated, whereby LDL is absorbed into the cell. The plasma cholesterol decreases as a result.
Taking and recordingThe most important sources of cholesterol are: cheese, egg yolks, cow meat, pork, chicken meat and shrimp. It is not often found in plants
Most of the cholesterol that is taken is esterified, and esterified cholesterol is poorly absorbed. The cholesterol that is absorbed in the intestines is transported in chylomicrons to the liver and peripheral cells. The cholesterol that is absorbed by intestinal cells is packaged in the liver in Very Low Density Lipoprotein (VLDL). The triacylglycerols (TAGs) from these VLDL particles are hydrolyzed in peripheral tissues by lipoprotein lipase (LPL). This creates VLDL remnants (remnants), these remnants are also called Intermediate Density Lipoprotein (IDL) particles.
IDL and LDL exchange cholesterol with HDL that exchanges TAGs. IDL and LDL deliver these particles to the liver. Because they are very small, they can go through the vascular wall. IDL and LDL bind to the LDL receptor and thus end up in lysosomes. The lysosomal enzymes then hydrolyze the cholesterol esters from LDL and IDL and then release the cholesterol to the cytoplasm. The activity of the LDL receptor depends on the intracellular cholesterol concentration. Ezetimibe inhibits the absorption of cholesterol via the NPC1L1 channel in the intestine. When someone takes less cholesterol through food, this will hardly lead to a decrease in plasma cholesterol, because less intake leads to more production of cholesterol in the cells.
Removal of cholesterolFree cholesterol is removed from our body in the form of free cholesterol or in the form of bile salts in the bile. The majority of bile salts are absorbed in the small intestine and then returned to the liver. This cycle in which a substance passes through the liver and the intestine several times is called the enterohepatic cycle.
Cholestyramine inhibits the enterohepatic cycle. The liver must make more bile salts, the plasma cholesterol will decrease, the LDL receptors will become more active and the cells will start producing more cholesterol themselves. Cellular cholesterol is removed by the High Density Lipid Protein (HDL). LCAT is made in the liver, it contains HDL. It esterifies the cholesterol that the HDL has received from cells.