Low-density lipoprotein (LDL) is one of the five major groups of lipoproteins, which in order of size, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, that enable transport of cholesterol within the water-based bloodstream. Studies have shown that higher levels of type-B LDL particles (as opposed to type-A LDL particles) promote health problems and cardiovascular disease, they are often informally called the bad cholesterol particles, (as opposed to HDL particles, which are frequently referred to as good cholesterol or healthy cholesterol particles).
Blood Tests typically report LDL-C, the amount of cholesterol contained in LDL. In clinical context, mathematically calculated estimates of LDL-C are commonly used to estimate how much low density lipoproteins are driving progression of atherosclerosis.
Direct LDL measurements are also available and better reveal individual issues but are less often promoted or done due to slightly higher costs and being available from only a couple of laboratories in the United States. In 2008, the ADA and ACC recognized direct LDL particle measurement by NMR as superior for assessing individual risk of cardiovascular events.
Each native LDL particle contains a single apolipoprotein B-100 molecule (Apo B-100, a protein that has 4536 amino acid residues and a mass of 514 kDa), which circulates the fatty acids, keeping them soluble in the aqueous environment. In addition, LDL has a highly-hydrophobic core consisting of polyunsaturated fatty acid known as linoleate and about 1500 esterified cholesterol molecules. This core is surrounded by a shell of phospholipids and unesterified cholesterol, as well as the single copy of Apo B-100. LDL particles are approximately 22 nm (0.00000087 in.) in diameter and have a mass of about 3 million daltons, but since LDL particles contain a changing number of fatty acids, they actually have a distribution of mass and size. Determining structure of LDL has been a tough task because of its heterogeneous structure. First structure of LDL at human body temperature in native condition has been recently found using cryo-electron microscopy and it has resolution of 16 Angstrom.
LDL subtype patterns
LDL particles vary in size and density, and studies have shown that a pattern that has more small dense LDL particles, called Pattern B, equates to a higher risk factor for coronary heart disease (CHD) than does a pattern with more of the larger and less dense LDL particles (Pattern A). This is because the smaller particles are more easily able to penetrate the endothelium. Pattern I, for intermediate, indicates that most LDL particles are very close in size to the normal gaps in the endothelium (26 nm). According to one study, sizes 19.0 to 20.5 nm were designated as pattern B and LDL sizes 20.6–22 nm were designated as pattern A.
Some in the medical community have suggested the correspondence between Pattern B and CHD is stronger than the correspondence between the LDL number measured in the standard lipid profile test. Tests to measure these LDL subtype patterns have been more expensive and not widely available, so the common lipid profile test is used more commonly.
There has also been noted a correspondence between higher triglyceride levels and higher levels of smaller, denser LDL particles and alternately lower triglyceride levels and higher levels of the larger, less dense LDL.
With continued research, decreasing cost, greater availability and wider acceptance of other lipoprotein subclass analysis assay methods, including NMR spectroscopy, research studies have continued to show a stronger correlation between human clinically obvious cardiovascular event and quantitatively-measured particle concentrations.
Transport into the cell
When a cell requires cholesterol, it synthesizes the necessary LDL receptors, and inserts them into the plasma membrane. The LDL receptors diffuse freely until they associate with clathrin-coated pits. LDL particles in the blood stream bind to these extracellular LDL receptors. The clathrin-coated pits then form vesicles that are endocytosed into the cell.
After the clathrin coat is shed, the vesicles deliver the LDL and their receptors to early endosomes, onto late endosomes to lysosomes. Here the cholesterol esters in the LDL are hydrolysed. The LDL receptors are recycled back to the plasma membrane.
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