Lipoprotein catabolism

D5. Deckelbaum, R. J., Eisenberg, S., Fainaru, M., Barenholz, Y., and Olivecrona, T., In vitro production of human plasma low density lipoprotein-like particles A model for very low density lipoprotein catabolism. /. Biol. Chem. 254, 6079-6087 (1979). 

M24. Malmendier, C. L., Delctoix, C., and Fontaine, M., Effect of sialic acid removal on human low density lipoprotein catabolism in vivo. Atherosclerosis 37, 277-284 (1980). M25. Malmendier, C. L., Paroutaud, P., and Ameryckx, J. P., Partial amino acid sequence of three new apolipoproteins isolated from human high density lipoproteins. FEBS Lett. 109, 43-44 (1980). 

The liver is an important organ for lipoprotein metabolism. It is not only a major site of lipoprotein synthesis, but also the most important site of lipoprotein catabolism. Most of the apolipoproteins, as well as the cholesterol and cholesterylester moieties of all circulating plasma lipoproteins, are catabolized in the liver. This makes sense because the liver is the only organ capable of degrading substantial amounts of cholesterol. The resulting bile acids are secreted in the bile, together with undegraded cholesterol. A small part of the bile acids and cholesterol escapes the enterohepatic circulation and forms the major route of cholesterol excretion from the body. 

Tissue Sites of Plasma (Very) Low Density Lipoprotein Catabolism... 

The dynamic nature of lipoprotein structure and the importance of the physical processes of spontaneous transfer of lipid and apoprotein components in lipoprotein catabolism is shown in Fig. 8. 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

CHYLOMICRONS VERY LOW DENSITY LIPOPROTEINS ARE RAPIDLY CATABOLIZED... 

Chappell DA, Medh JD Receptor-mediated mechanisms of lipoprotein remnant catabolism. Prog Lipid Res 1998 37 393. 

The reason for the cholesterol-lowering effect of polyunsaturated fatty acids is still not fully understood. It is clear, however, that one of the mechanisms involved is the up-regulation of LDL receptors by poly-and monounsaturated as compared with saturated fatty acids, causing an increase in the catabolic rate of LDL, the main atherogenic lipoprotein. In addition, saturated fatty acids cause the formation of smaller VLDL particles that contain relatively more cholesterol, and they are utilized by extrahepatic tissues at a slower rate than are larger particles—tendencies that may be regarded as atherogenic. 

TNF (17.5) Monocyte/macrophage, lymphocyte, neutrophil, endothelium, fibroblast, keratinocyte Activation of T and B cells, natural killer cells, neutrophils, and osteoblasts. Stimulation of endothelial cells to release chemotactic proteins, NO and PGI2. Tumoricidal activity. Induces fever, sleep, hepatic acute phase protein synthesis, catabolism, ACTH release. Lead to myocardial depression, hypotension/shock, hypercoagulability, and death. Stimulates production of IL-1, IL-6, IL-8, IFN-y, and H202. Suppression of cytochrome P-450, thyroglobulin, and lipoprotein lipase. Induces complement activation, release of eicosanoids, including PAF. Procoagulant activity. 

High density lipoprotein (HDL) 50 1-5 20 30 45-55 Transport of cholesterol from peripheral tissues to the liver for catabolism... 

Observations in different types of primary hyperlipidemia revealed in general an inverse correlation between Lp(a) concentrations and plasma triglyceride and triglyceride-rich lipoprotein concentrations in hypertriglyceridemic subjects (A 10, B22, H30, W11). As far as this observation is not troubled by technical problems in the analysis (E8), the possibility exists that Lp(a) catabolism is partly related to the catabolism of triglyceride-rich and/or cholesterol-rich particles (P10, R16). 

Schonfeld, G., Gulbrandsen, C. L., Wilson, R. B., and Lees, R. S., Catabolism of human very low-density lipoproteins in monkeys the appearance of human very low-density lipoprotein peptides in monkey high-density lipoproteins. Biochim. Biophya. Ada 270, 426-432 (1972). 

High-density lipoproteins are formed in the liver and intestines as a result of catabolism of chylomicrons and very low-density lipoproteins, and in comparison with other lipoproteins, they contain considerably more cholesterol esters with unsaturated fatty acids, as well as phospholipids and specific proteins. 

Dextrothyroxine speeds up the decomposition of cholesterol and lipoproteins, thus activating catabolism of cholesterol in the liver, which results in cholesterol being more intensively transformed into bile salts. It lowers the level of low-density lipoproteins in the plasma and very low-density lipoproteins in fatty tissue. It is recommended for treating hyperlipoproteinemia. Synonyms of this drug are choloxin, lizolipin, natexin, travenon, and others. 

Other- Liver disease with impaired hemostasis severe renal disease. Hyperlipidemia Heparin may increase free fatty acid serum levels by induction of lipoprotein lipase. The catabolism of serum lipoproteins by this enzyme produces lipid fragments that are rapidly processed by the liver. Patients with dysbetalipoproteinemia (type III) are unable to catabolize the lipid fragments, resulting in hyperlipidemia. 

Increased secretion and decreased catabolism of very low density lipoprotein. Arterioscler Thromb 1991 CN115... 

Mechanism of Action An antihyperlipidemic that enhances synthesis of lipoprotein lipase and reduces triglyceride-rich lipoproteins and VLDLs. Therapeutic Effect Increases VLDL catabolism and reduces total plasma triglyceride levels. Pharmacokinetics Well absorbed from the GI tract. Absorption increased when given with food. Protein binding 99%. Rapidly metabolized in the liver to active metabolite. Excreted primarily in urine lesser amount in feces. Not removed by hemodialysis. Half-life 20 hr. 

Decreases catabolism of apo AI treduces VLDL secretion from liver Increases HDL decreases lipoprotein(a) [Lp(a)], LDL, and triglycerides Low HDL elevated VLDL, LDL, Lp(a) Oral large doses Toxicity Gastric irritation, flushing, low incidence of hepatic toxicity may reduce glucose tolerance... 

Patients with HL deficiency present with hypercholesterolemia and hypertriglyceridemia, and accumulate VLDL remnants, triglyceride-rich LDL, and HDL [84]. These remnants mainly derive from a reduced catabolism of apoB-containing lipoproteins [82]. The disorder appears to be inherited in an autosomal recessive trait and is associated with an increased risk for coronary artery disease [8]. 

Familial hypercholesterolemia (FH) is one of the most common genetic disorders in lipoprotein metabolism, and causes elevated cholesterol levels. This autosomal dominant disorder with a prevalence of about 1/500 in Western countries is caused by mutations in the LDLR gene. The LDLR defect impairs the catabolism of LDL and results in elevation of plasma LDL-cholesterol. Untreated heterozygous FH patients have 2-3 times elevated cholesterol levels and have a 100-fold increased risk to die... 

As the lipoproteins are depleted of triacylglycerol, the particles become smaller. Some of the surface molecules (apoproteins, phospholipids) are transferred to HDL. In the rat, remnants that result from chylomicron catabolism are removed by the liver. The uptake of remnant VLDL also occurs, but much of the triacylglycerol is further degraded by lipoprotein lipase to give the intermediate-density lipoprotein (IDL). This particle is converted into LDL via the action of lipoprotein lipase and enriched in cholesteryl ester via transfer from HDL by the cholesteryl ester transfer protein. The half-life for clearance of chylomicrons from plasma of humans is 4-5 min. Patients with the inherited disease, lipoprotein lipase deficiency, clear chylomicrons from the plasma very slowly. When on a normal diet, the blood from these patients looks like tomato soup. A very-low-fat diet greatly relieves this problem. 

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