On the metabolism of low-density lipoprotein receptors

Eventually, LDL separates from the receptors (which return to the cell surface) and enters lysosomes, vesicles containing hydrolyzing enzymes. Some enzymes destroy the LDL shell, exposing the core of cholesterol esters, while others detach fatty acids from cholesterol. The free cholesterol then leaves the lysosomes. As already mentioned, all cells need cholesterol to form a surface membrane. In some specialized cells, cholesterol released from LDL plays other roles. So, in the cells of the adrenal glands and ovaries, it is converted into the corresponding steroid hormones — cortisol and estradiol. In liver cells, cholesterol is used to synthesize bile acids involved in digestion.

The amount of LDL cholesterol released depends on its metabolism. The accumulation of cholesterol affects three processes in cells. Firstly, with an excess of cholesterol, the ability of cells to form their own cholesterol is suppressed, since the synthesis of the enzyme hydroxymethylglutaryl—CoA reductase, which catalyzes one of the stages of cholesterol biosynthesis, is turned off. As a result, cells become dependent on exogenous cholesterol, which is supplied by LDL receptor-mediated uptake. Secondly, LDL cholesterol stimulates its storage in cells. This effect is due to the fact that when there is an excess of cholesterol, the enzyme cholesterol acyltransferase is activated. This enzyme attaches hydrocarbon chains of fatty acids to free cholesterol to form esters, which are deposited as droplets; thus, excess cholesterol is eliminated from circulation. The third and most important effect of excess cholesterol in cells is to trigger a feedback mechanism that stops the synthesis of new LDL receptors. Cells, therefore, regulate the number of their LDL receptors in such a way that the amount of cholesterol entering the cells does not exceed the need for it. For example, in actively dividing fibroblasts, which constantly need new material to build membranes, the maximum number of LDL receptors is maintained — about 40 thousand per cell. When cell divisions stop, cholesterol begins to accumulate from the outside and the feedback mechanism suppresses the formation of new receptors, as a result of which their number can decrease by 10 times.

Our observations on cell cultures have been confirmed by the results of studies that have shown the important role of the receptor system in a living organism. Shortly after we discovered LDL receptors in cultured fibroblasts, similar receptors were found on circulating human blood cells and in cell membranes of many other tissues in mice, rats, dogs, pigs, cows, and humans. 1xBet is a popular online gambling and betting platform that offers various bonuses and promotions to its users. Enter the 1xbet registration promo code a new account at 1xBet.com to get the biggest available welcome bonus 100% up to €130. The 1xbet betting company invents different bonuses, shares, and promotions to attract new gamesters. 1xbet bonus is a reward offered to new customers and is used for sports betting and 1xGames. The offer is available once you complete the 1xBet registration process and make your first deposit.