Lipoproteins transport

The LDL particles contain one apoB-100 as the structural protein and are the major cholesterol-transporting lipoproteins in human blood. Clearance of LDL from blood is mediated by the interaction of apoB-100 with the LDLR. Genetic defects either in the receptor binding region of apoB-100 or in the LDLR lead to decreased clearance of LDL and hence to their accumulation in the blood. The major metabolic pathways of the lipoprotein metabolism are shown in Fig. 5.2.1. 

There are a large number of target genes for PPARa, including both mitochondrial and peroxisomal jl-oxidation enzymes, apolipoproteins, fatty acid transporters, lipoprotein lipase, CYP4A, and thioesterases. As PPARa is located in and particularly abundant in the liver, this is the target organ for peroxisomal proliferator chemicals. 

Although several lipoproteins are considered to play a role in atherogenesis [VLDL, LDL and Lp(a)j, LDL cholesterol (LDL-C) is the primary target of therapy. The risk of CHD is inversely related to levels of HDL, because HDL is responsible for reverse cholesterol transport. Lipoprotein disorders can involve abnormalities in lipid metabolism (e.g., synthesis, transport, and catabolism). Attainment of a lipid profile must be made after a 9- to 12-hour fast. 

LDL, the major cholesterol transport lipoprotein, having virtually only apolipoprotein B-lOO, is mostly derived from VLDL catabolism and cellular synthesis. When fasting and when normal subjects are on low-fat intake, most cholesterol is synthesized and used in the extrahepatic organs, whereas most of the cholesterol carried by LDL is taken up by the liver for catabolism. In patients with homozygous familial hypercholesterolemia, enhanced synthesis of LDL may occur because LDL clearance is reduced as a consequence... 

See also Cholesterol, Fat Absorption and Transport, Lipoprotein Complexes in Fat Transport... 

Cholesterol is biosynthesized in the liver trans ported throughout the body to be used in a va riety of ways and returned to the liver where it serves as the biosynthetic precursor to other steroids But cholesterol is a lipid and isn t soluble in water How can it move through the blood if it doesn t dis solve in if The answer is that it doesn t dissolve but IS instead carried through the blood and tissues as part of a lipoprotein (lipid + protein = lipoprotein) The proteins that carry cholesterol from the liver are called low density lipoproteins or LDLs those that return it to the liver are the high-density lipoproteins or HDLs If too much cholesterol is being transported by LDL or too little by HDL the extra cholesterol builds up on the walls of the arteries caus mg atherosclerosis A thorough physical examination nowadays measures not only total cholesterol con centration but also the distribution between LDL and HDL cholesterol An elevated level of LDL cholesterol IS a risk factor for heart disease LDL cholesterol is bad cholesterol HDLs on the other hand remove excess cholesterol and are protective HDL cholesterol IS good cholesterol... 

Cholesterol is biosynthesized in the liver, transported throughout the body to be used in a variety of ways, and returned to the liver where it serves as the biosynthetic precursor to other steroids. But cholesterol is a lipid and isn t soluble in water. How can it move through the blood if it doesn t dissolve in it The answer is that it doesn t dissolve, but is instead carried through the blood and tissues as part of a lipoprotein (lipid + protein = lipoprotein). 

LIPOPROTEINS. Blood plasma lipoproteins are prominent examples of the class of proteins conjugated with lipid. The plasma lipoproteins function primarily in the transport of lipids to sites of active membrane synthesis. Serum levels of low density lipoproteins (LDLs) are often used as a clinical index of susceptibility to vascular disease. 

We turn now to the biosynthesis of lipid structures. We begin with a discussion of the biosynthesis of fatty acids, stressing the basic pathways, additional means of elongation, mechanisms for the introduction of double bonds, and regulation of fatty acid synthesis. Sections then follow on the biosynthesis of glyc-erophospholipids, sphingolipids, eicosanoids, and cholesterol. The transport of lipids through the body in lipoprotein complexes is described, and the chapter closes with discussions of the biosynthesis of bile salts and steroid hormones. 

Transport of Many Lipids Occurs via Lipoprotein Complexes... 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

HDL and VLDL are assembled primarily in the endoplasmic reticulum of the liver (with smaller amounts produced in the intestine), whereas chylomicrons form in the intestine. LDL is not synthesized directly, but is made from VLDL. LDL appears to be the major circulatory complex for cholesterol and cholesterol esters. The primary task of chylomicrons is to transport triacylglycerols. Despite all this, it is extremely important to note that each of these lipoprotein classes contains some of each type of lipid. The relative amounts of HDL and LDL are important in the disposition of cholesterol in the body and in the development of arterial plaques (Figure 25.36). The structures of the various... 

Lipoprotein (Chapter 27 Focus On) A complex molecule with both lipid and protein parts that transports lipids through the body. 

Cholesterol, which is water-insoluble, is transported through the blood in the form of soluble protein complexes known as lipoproteins. 

Gene activated Lipoprotein lipase fatty acid transporter protein adipocyte fatty acid binding protein acyl-CoA synthetase malic enzyme GLUT-4 glucose transporter phosphoenolpyruvate carboxykinase... 

Lipoprotein metabolism is the process by which hydrophobic lipids, namely triglycerides and cholesterol, are transported within the interstitial fluid and plasma. It includes the transport of energy in the form of triglycerides from intestine and liver to muscles and adipose, as well as the transport of cholesterol both from intestine and liver to peripheral tissues, as well as from peripheral tissues back to the liver. 

Lipoprotein Metabolism. Figure 3 HDL metabolism and reverse cholesterol transport. 

The main transport form of lipids in the cir culation. They are spherical macromolecules of 10-1200 nm diameter-composed of a core of neutral lipids (mostly cholesterol ester and triglycerides) surrounded by an amphipathic shell of polar phospholipids and cholesterol. Embedded in the shell of lipoproteins are apolipoproteins that are essential for assembly of theparticles in tissues that secrete lipoproteins, and for their recognition by target cells. 

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