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After internalization, the receptors dissociate from their ligands when they are exposed to lower pH in endosomes. After dissociation, the receptor folds back on itself to obtain a closed conformation and recycles to the cell surface. [22] The rapid recycling of LDL receptors provides an efficient mechanism for delivery of cholesterol to cells.
When LDL receptors bind LDL particles in the bloodstream, the clathrin-coated pits are endocytosed into the cell. [citation needed] Vesicles containing LDL receptors bound to LDL are delivered to the endosome. In the presence of low pH, such as that found in the endosome, LDL receptors undergo a conformation change, releasing LDL. LDL is then ...
In FH, LDL receptor function is reduced or absent, [9] and LDL circulates for an average duration of 4.5 days, resulting in significantly increased level of LDL cholesterol in the blood with normal levels of other lipoproteins. [6] In mutations of ApoB, reduced binding of LDL particles to the receptor causes the increased level of LDL cholesterol.
In humans, excess cholesterol in the blood is captured by low-density lipoprotein (LDL) and removed by the liver via endocytosis of the LDL receptor. [4] Recent evidence indicates that the members of the LDL receptor gene family are active in the cell signalling pathways between specialized cells in many, if not all, multicellular organisms. [5 ...
interference with the heart's blood supply, typically by clogging of coronary, or other, arteries. Ischemia means lack of oxygen which necessarily follows from one or more blocked arteries. Coxsackie B4 virus a virus which can trigger an auto-immune reaction which eventually results in a (mistaken) auto-immune attack on the beta cells.
Fibrates may decrease LDL, though generally to a lesser degree than statins. Similar to statins, the risk of muscle damage exists. Nicotinic acid, like fibrates, is also well suited for lowering triglycerides by 20–50%. It may also lower LDL by 5–25% and increase HDL by 15–35%. Niacin may cause hyperglycemia and may also cause liver damage.
Insulin resistance desensitizes insulin receptors, preventing insulin from lowering blood sugar levels. [38] The leading cause of hyperglycemia in type 2 diabetes is the failure of insulin to suppress glucose production by glycolysis and gluconeogenesis due to insulin resistance. [39]
Downregulation of receptors can also occur when receptors have been chronically exposed to an excessive amount of a ligand, either from endogenous mediators or from exogenous drugs. This results in ligand-induced desensitization or internalization of that receptor. This is typically seen in animal hormone receptors.