Low-density lipoprotein
Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water.[1] These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density naming convention), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL has been associated with the progression of atherosclerosis.
"LDL" redirects here. For other uses, see LDL (disambiguation).Overview[edit]
Lipoproteins transfer lipids (fats) around the body in the extracellular fluid, making fats available to body cells for receptor-mediated endocytosis.[2][3] Lipoproteins are complex particles composed of multiple proteins, typically 80–100 proteins per particle (organized by a single apolipoprotein B for LDL and the larger particles). A single LDL particle is about 220–275 angstroms in diameter, typically transporting 3,000 to 6,000 fat molecules per particle, and varying in size according to the number and mix of fat molecules contained within.[4] The lipids carried include all fat molecules with cholesterol, phospholipids, and triglycerides dominant; amounts of each vary considerably.[5]
A good clinical interpretation of blood lipid levels is that high LDL, in combination with a high amount of triglycerides, which indicates a high likelihood of the LDL being oxidised, is associated with increased risk of cardiovascular diseases.[6]
Biochemistry[edit]
Structure[edit]
Each native LDL particle enables emulsification, i.e. surrounding the fatty acids being carried, enabling these fats to move around the body within the water outside cells. Each 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), along with 80 to 100 additional ancillary proteins. Each LDL has a highly hydrophobic core consisting of polyunsaturated fatty acid known as linoleate and hundreds to thousands (about 1500 commonly cited as an average) of esterified and unesterified cholesterol molecules. This core also carries varying numbers of triglycerides and other fats and 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.) to 27.5 nm in diameter and have a mass of about 3 million daltons.[7] Since LDL particles contain a variable and changing number of fatty acid molecules, there is a distribution of LDL particle mass and size.[4] Determining the structure of LDL has been a tough task because of its heterogeneous structure. However, the structure of LDL at human body temperature in native condition, with a resolution of about 16 Angstroms using cryogenic electron microscopy, has been described in 2011.[8]
Research[edit]
Gene editing[edit]
In 2021, scientists demonstrated that CRISPR gene editing can decrease blood levels of LDL cholesterol in Macaca fascicularis monkeys for months by 60% via knockout of PCSK9 in the liver.[69][70]