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Lipoprotein-X (Lp-X) is an abnormal low density lipoprotein found in cholestasis.
| This article includes a list of references, related reading, or external links, but its sources remain unclear because it lacks inline citations .(March 2019) |
Lipoprotein-X (Lp-X) is an abnormal low density lipoprotein found in cholestasis.
Lipoprotein-X is a lamellar particle of 30 to 70 nm in diameter as revealed by electron microscopy. It is characterized by its high content of phospholipids (66% by weight) and unesterified cholesterol (22%), and its low content of protein (6%), cholesterol esters (3%), and triglycerides (3%). The protein component is dominated by albumin, located in the core, and by apolipoprotein C, located on the surface of the particle. Using zonal ultracentrifugation, lipoprotein-X can be divided into three distinct populations: Lp-X1, Lp-X2, and Lp-X3, differing in density and apolipoprotein composition.
The pathogenesis of lipoprotein-X in cholestasis is not totally resolved. Normally, the liver excretes lipoprotein complexes into the bile showing phospholipid and unesterified cholesterol concentrations similar to Lipoprotein-X. The in vitro incubation of these bile lipoproteins with serum or albumin leads to the appearance of Lp-X–like particles. These findings suggest that the reflux of bile into the plasma compartment causes the formation of lipoprotein-X in cholestasis as a result of a physicochemical, nonmetabolic process. On the other hand, lipoprotein-X particles found in familial LCAT deficiency are identical to those in cholestasis regarding ultrastructure and biochemical composition. It has been supposed that reduced LCAT activities, common in patients with hepatocellular disease, cause, alone or in combination with other factors, the formation of Lipoprotein-X in cholestasis. Lipoprotein-X is mainly removed by the reticuloendothelial system of the liver and the spleen, as shown by studies using radioactively labeled lipoprotein-X in rats. Other organs, such as the kidney, also actively clear Lipoprotein-X from the plasma.
Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle. HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle.
Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons, 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 is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries.
A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role.
Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. VLDL is assembled in the liver from triglycerides, cholesterol, and apolipoproteins. VLDL is converted in the bloodstream to low-density lipoprotein (LDL) and intermediate-density lipoprotein (IDL). VLDL particles have a diameter of 30–80 nm. VLDL transports endogenous products, whereas chylomicrons transport exogenous (dietary) products. In the early 2010s both the lipid composition and protein composition of this lipoprotein were characterised in great detail.
Chylomicrons, also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), phospholipids (6–12%), cholesterol (1–3%), and proteins (1–2%). They transport dietary lipids from the intestines to other locations in the body. ULDLs are one of the five major groups of lipoproteins that enable fats and cholesterol to move within the water-based solution of the bloodstream. A protein specific to chylomicrons is ApoB48.
A lacteal is a lymphatic capillary that absorbs dietary fats in the villi of the small intestine.
Apolipoproteins are proteins that bind lipids to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph.
Apolipoprotein C-II, or apolipoprotein C2 is a protein that in humans is encoded by the APOC2 gene.
Lecithin–cholesterol acyltransferase is an enzyme, in many animals including humans, that converts free cholesterol into cholesteryl ester, which is then sequestered into the core of a lipoprotein particle, eventually making the newly synthesized HDL spherical and forcing the reaction to become unidirectional since the particles are removed from the surface. The enzyme is bound to high-density lipoproteins (HDLs) (alpha-LCAT) and LDLs (beta-LCAT) in the blood plasma. LCAT deficiency can cause impaired vision due to cholesterol corneal opacities, anemia, and kidney damage. It belongs to the family of phospholipid:diacylglycerol acyltransferases.
Lecithin cholesterol acyltransferase deficiency is a disorder of lipoprotein metabolism. The disease has two forms: Familial LCAT deficiency, in which there is complete LCAT deficiency, and Fish-eye disease, in which there is a partial deficiency.
Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.
Lipoprotein(a) is a low-density lipoprotein variant containing a protein called apolipoprotein(a). Genetic and epidemiological studies have identified lipoprotein(a) as a risk factor for atherosclerosis and related diseases, such as coronary heart disease and stroke.
Apolipoprotein AI(ApoA-I) is a protein that in humans is encoded by the APOA1 gene. As the major component of HDL particles, it has a specific role in lipid metabolism.
Apolipoprotein C-III also known as apo-CIII, and apolipoprotein C3, is a protein that in humans is encoded by the APOC3 gene. Apo-CIII is secreted by the liver as well as the small intestine, and is found on triglyceride-rich lipoproteins such as chylomicrons, very low density lipoprotein (VLDL), and remnant cholesterol.
Endothelial lipase (LIPG) is a form of lipase secreted by vascular endothelial cells in tissues with high metabolic rates and vascularization, such as the liver, lung, kidney, and thyroid gland. The LIPG enzyme is a vital component to many biological processes. These processes include lipoprotein metabolism, cytokine expression, and lipid composition in cells. Unlike the lipases that hydrolyze Triglycerides, endothelial lipase primarily hydrolyzes phospholipids. Due to the hydrolysis specificity, endothelial lipase contributes to multiple vital systems within the body. On the contrary to the beneficial roles that LIPG plays within the body, endothelial lipase is thought to play a potential role in cancer and inflammation. Knowledge obtained in vitro and in vivo suggest the relations to these conditions, but human interaction knowledge lacks due to the recent discovery of endothelial lipase. Endothelial lipase was first characterized in 1999. The two independent research groups which are notable for this discovery cloned the endothelial lipase gene and identified the novel lipase secreted from endothelial cells. The anti-Atherosclerosis opportunity through alleviating plaque blockage and prospective ability to raise High-density lipoprotein (HDL) have gained endothelial lipase recognition.
Blood lipids are lipids in the blood, either free or bound to other molecules. They are mostly transported in a phospholipid capsule, and the type of protein embedded in this outer shell determines the fate of the particle and its influence on metabolism. Examples of these lipids include cholesterol and triglycerides. The concentration of blood lipids depends on intake and excretion from the intestine, and uptake and secretion from cells. Hyperlipidemia is the presence of elevated or abnormal levels of lipids and/or lipoproteins in the blood, and is a major risk factor for cardiovascular disease.
Phospholipid transfer protein is a protein that in humans is encoded by the PLTP gene.
Apolipoprotein F is a protein that in humans is encoded for by the APOF gene. The product of this gene is one of the minor apolipoproteins found in plasma. This protein forms complexes with lipoproteins and may be involved in transport and/or esterification of cholesterol.
Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream.