Lipoproteins intermediate density lipoprotein

Endothelial-anchored enzyme in liver primarily responsible for hydrolysis of triglycerides and phospholipids in Intermediate Density Lipoproteins (IDL) and High Density Lipoproteins (HDL). 

Interleukins Intermediate Filaments Intermediate-density Lipoprotein (DDL) Intermittent Claudication Internalization... 

Abbreviations HDL, high-density iipoproteins IDL, intermediate-density lipoproteins LDL, low-density lipoproteins VLDL, very low density lipoproteins. 

Reaction with lipoprotein lipase results in the loss of approximately 90% of the triacylglycerol of chylomicrons and in the loss of apo C (which remrns to HDL) but not apo E, which is retained. The resulting chy-lotnicron remnant is about half the diameter of the parent chylomicron and is relatively enriched in cholesterol and cholesteryl esters because of the loss of triacylglycerol (Figure 25-3). Similar changes occur to VLDL, with the formation of VLDL remnants or IDL (intermediate-density lipoprotein) (Figure 25-4). 

FIGURE 9. Endogenous lipoprotein metabolism. In liver cells, cholesterol and triglycerides are packaged into VLDL particles and exported into blood where VLDL is converted to IDL. Intermediate-density lipoprotein can be either cleared by hepatic LDL receptors or further metabolized to LDL. LDL can be cleared by hepatic LDL receptors or can enter the arterial wall, contributing to atherosclerosis. Acetyl CoA, acetyl coenzyme A Apo, apolipoprotein C, cholesterol CE, cholesterol ester FA, fatty acid HL, hepatic lipase HMG CoA, 3-hydroxy-3-methyglutaryl coenzyme A IDL, intermediate-density lipoprotein LCAT, lecithin-cholesterol acyltransferase LDL, low-density lipoprotein LPL, lipoprotein lipase VLDL, very low-density lipoprotein. 

IDE IF Intermediate density lipoprotein Initiation factor NAD+ Oxidized nicotinamide adenine dinucleotide... 

D. The lipoproteins include chylomicrons, HDLs, intermediate-density lipoproteins (IDLs), LDLs, and VLDLs, which differ by size, density, and composition of proteins and lipids. 

Partial summary of lipoprotein metabolism in humans. I to VII are sites of action of hypolipidemic drugs. I, stimulation of bile acid and/or cholesterol fecal excretion II, stimulation of lipoprotein lipase activity III, inhibition of VLDL production and secretion IV, inhibition of cholesterol biosynthesis V, stimulation of cholesterol secretion into bile fluid VI, stimulation of cholesterol conversion to bile acids VII, increased plasma clearance of LDL due either to increased LDL receptor activity or altered lipoprotein composition. CHOL, cholesterol IDL, intermediate-density lipoprotein. 

The loss of triacylglycerol converts some VLDL to VLDL remnants (also called intermediate density lipoprotein, IDL) further removal of triacylglycerol from VLDL produces low-density lipoprotein (LDL) (Table 21-2). Very rich in cholesterol and cholesteryl esters and containing apoB-100 as their major apoli-poprotein, LDLs carry cholesterol to extrahepatic tissues that have specific plasma membrane receptors that recognize apoB-100. These receptors mediate the uptake of cholesterol and cholesteryl esters in a process described below. 

Production of LDL from VLDL in the plasma With these modifications, the VLDL is converted in the plasma to LDL. An intermediate-sized particle, the intermediate-density lipoprotein (IDL) or VLDL remnant, is observed during this transition. IDLs can also be taken up by cells through receptor-mediated endocytosis that uses apo E as the ligand. [Note Apolipoprotein E is normally present in three isoforms, E2, E3, and E4. Apo E2 binds poorly to receptors, and patients who are homozygotic for apo E2 are deficient in the clearance of chylomicron remants and IDLs. The individuals have familial type III hyperlipoproteinemia (familial dysbetalipoproteinemia, or broad beta disease), with hypercholesterolemia and premature atherosclerosis. Not yet understood is the fact that the E4 isoform confers increased susceptibility to late-onset Alzheimer disease.]... 

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. 

Lipoproteins are particles with hydrophobic core regions containing cholesteryl esters and triglycerides. Unesterified cholesterol, phospholipids, and apoproteins surround the core. Certain lipoproteins contain very high-molecular-weight B proteins that exist in two forms B48, which is formed in the intestine and found in chylomicrons and their remnants and B100, synthesized in liver and found in VLDL, VLDL remnants (intermediate-density lipoproteins IDL), LDL (formed from VLDL), and the Lp(a) lipoproteins. 

Very low density liporoteins (VLDLs), intermediate density lipoproteins... 

The size of the VLDL particle in plasma diminishes and its density increases as triglyceride is hydrolyzed by endothelial lipoprotein lipase, and the particles are thus converted to intermediate-density lipoproteins (IDL) (B32, S35). The IDL detach from the endothelium, and some are taken up by hepatic B-100, E receptors. The remaining particles in the circulation are further depleted of some cholesteryl ester (by an unknown mechanism), and most of the remaining triglyceride (probably by hepatic triglyceride lipase, in the liver sinusoids) (D5). Hie resulting LDL particles are largely composed of cholesteryl ester as the core lipid and apoB-100 as the apolipoprotein. 

ApoE-containing VLDL in hyperlipidemic subjects has been shown to be both the product of particles less rich in apoE (as judged by the apoE apoC ratio) and the precursor of apoE-rich intermediate-density lipoprotein (N2). In cholesterol-fed dogs (F5) and humans with Type III hyperlipoproteinemia (F5, K3) there is evidence (based on the form of apoB, B-48, or B-100, and the response to fasting) that apoE-rich (3-VLDL contains remnants of both VLDL and chylomicrons. 

M46. Murase, T., and Hakura, H., Accumulation of intermediate density lipoprotein in plasma after intravenous administration of hepatic triglyceride lipase antibody in rats. Atherosclerosis 38, 293-300 (1981). 

Soutar, A. K., Myant, N. B., and Thompson, G. R., The metabolism of very low density and intermediate density lipoproteins in patients with familial hypercholesterolaemia. Atherosclerosis 43, 217-231 (1982). 

The use of plant sterols—(3-sitostcrol and sitostanol in consumer products to decrease cholesterol is supported by numerous clinical studies that document their efficacy in lowering mild hyperlipidemia (Jones et al., 1998 Hallikainen and Uusitupa, 1999). Although the normal diet contains plant sterols that range from 160 to 360 mg/day, a 5- to 10-fold increase is required to exert a cholesterol-lowering effect. Consumer products with increased amounts of phytosterols that exceed the content found in the diet have been made available to the consumer. In evaluating the efficacy of including sitostanol ester in margarine as a dietary supplement for children with familial hypercholesterolemia (FH), it was found that serum total cholesterol (TC), intermediate density lipoprotein-cholesterol and LDL-cholesterol levels fell while the HDL-cholesterol/LDL-cholesterol ratio was elevated. 

Triacylglycerols and cholesterol are exported from the liver as nascent VLDL complexes, destined primarily to muscle and adipose tissues. The VLDL complex contains apolipoprotein B-lOO and acquires C-I, C-II, C-III and E from circulating HDL complexes. Fatty acids are released from VLDLs in the same way as chylomicrons, through the action of LPL. This action, coupled to a loss of certain apoproteins (the apo-Cs), converts VLDLs to intermediate-density lipoproteins (IDLs), also termed VLDL remnants. The apo-Cs are transferred to HDLs. The predominant remaining proteins are apo-B-100 and apo-E. Further loss of triacylglycerols converts IDLs to LDLs. 

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