High density lipoproteins function

High-density lipoprotein functions as a shuttle that moves cholesterol throughout the body. HDL binds and esterifies cholesterol released from the peripheral tissues and then transfers cholesteryl esters to the liver or to tissues that use cholesterol to synthesize steroid hormones. A specific receptor mediates the docking of the HDL to these tissues. The exact nature of the protective effect of HDL levels is not known however, a possible mechanism is discussed in Section... 

High-density lipoproteins (HDL) have much longer life spans in the body (5 to 6 days) than other lipoproteins. Newly formed HDL contains virtually no cholesterol ester. However, over time, cholesterol esters are accumulated through the action of lecithin cholesterol acyltransferase (LCAT), a 59-kD glycoprotein associated with HDLs. Another associated protein, cholesterol ester transfer protein, transfers some of these esters to VLDL and LDL. Alternatively, HDLs function to return cholesterol and cholesterol esters to the liver. This latter process apparently explains the correlation between high HDL levels and reduced risk of cardiovascular disease. (High LDL levels, on the other hand, are correlated with an increased risk of coronary artery and cardiovascular disease.)... 

Systemic treatment of 13-cis retinoic acid frequently leads to cheilitis and eye irritations (e.g., unspecific cornea inflammation). Also other symptoms such as headache, pruritus, alopecia, pains of joints and bone, and exostosis formation have been reported. Notably, an increase of very low density lipoproteins and triglycerides accompanied by a decrease of the high density lipoproteins has been reported in 10-20% of treated patients. Transiently, liver function markers can increase during oral retinoid therapy. Etretinate causes the side effects of 13-cis retinoid acid at lower doses. In addition to this, generalized edema and centrilobulary toxic liver cell necrosis have been observed. 

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

Narayanaswami, V., Maiorano, J. N., Dhanasekaran, P. et al. Helix orientation of the functional domains in apolipoprotein e in discoidal high density lipoprotein particles. /. Biol. Chem. 279 14273-14279, 2004. 

Lipoproteins are classified into five groups. In order of decreasing size and increasing density, these are chylomicrons, VLDLs (very-low-density lipoproteins), IDLs (inter-mediate-density lipoproteins), LDLs (low-density lipoproteins), and HDLs (high-density lipoproteins). The proportions of apoproteins range from 1 % in chylomicrons to over 50% in HDLs. These proteins serve less for solubility purposes, but rather function as recognition molecules for the membrane receptors and enzymes that are involved in lipid exchange. 

Although nicotinic acid and nicotinamide function identically as vitamins, their pharmacologic effects differ. In large doses (up to 6 g/day), nicotinic acid is effective in reducing serum lipids (low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides, and lipoprotein A. Nicotinic acid produces vasodilation and increased blood flow due to histamine release. Nicotinamide does not affect blood lipid levels or the cardiovascular system. 

Factor II), and Factors VII, VIII, IX, and X may increase. Sulfobromophthalein and other liver function test values may be increased the effects of medroxyprogesterone acetate on lipid metabolism are inconsistent. Both increases and decreases in total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (FIDL) cholesterol have been observed. 

In blood, lipids exist as lipoprotein particles, the main function of which is to transport lipids to and from various tissues and organs of the body. There is considerable interest in blood lipoproteins from the viewpoint of human health, especially obesity and cardiovascular diseases. Lipoproteins are classified into four groups on the basis of density, which is essentially a function of their triglyceride content, i.e. chylomicrons, very low density lipoprotein particles (VLDL), low density lipoprotein (LDL) particles and high density lipoprotein (HDL) particles, containing c. 98, 90, 77 and 45% total lipid, respectively (Figure 3.11). 

The plasma lipoproteins are spherical macromolecular complexes of lipids and specific proteins (apolipoproteins or apoproteins). The lipoprotein particles include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They differ in lipid and protein composition, size, and density (Figure 18.13). Lipoproteins function both to keep their component lipids soluble as they transport them in the plasma, and also to provide an efficient mechanism for transporting their lipid contents to (and from) the tissues. In humans, the transport system is less perfect than in other animals and, as a result, humans experience a yradual deposition of lipid—especially cholesterol—in tissues. This is a potentially life-threat-en ng occurrence when the lipid deposition contributes to plaque formation, causing the narrowing of blood vessels (atherosclerosis). 

The plasma lipoproteins include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They function to keep lipids (primarily triacylglyc-erol and cholesteryl esters) soluble as they transport them between tissues. Lipoproteins are composed of a neutral lipid core (containing triacylglycerol, cholesteryl esters, or both) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified cholesterol. Chylomicrons are assembled in intestinal mucosal cells from dietary lipids (primarily, triacylglycerol) plus additional lipids synthesized in these cells. Each nascent chylomicron particle has one molecule of apolipoprotein B-48 (apo B-48). They are released from the cells into the lymphatic system and travel to the blood, where they receive apo C-ll and apo E from HDLs, thus making the chylomicrons functional. Apo C-ll activates lipoprotein lipase, which degrades the... 

Aviram, M., et al. 1998. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest 101 1581. 

Clinical findings may include hypertrophied muscles, acne, oily skin, hirsutism in females, gynecomastia in males, and needle punctures. Edema and jaundice may develop in heavy users. Common laboratory abnormalities include elevated hemoglobin and hematocrit measurements, elevated low-density lipoprotein cholesterol and depressed high-density lipoprotein cholesterol levels. Liver function test results may be elevated, and luteinizing hormone levels are usually depressed. 

Lipoproteins are globular, micelle-like particles consisting of a hydrophobic core of triacylglycerols and cholesterol esters surrounded by an amphipathic coat of protein, phospholipid and cholesterol. The apolipoproteins (apoproteins) on the surface of the lipoproteins help to solubilize the lipids and target the lipoproteins to the correct tissues. There are five different types of lipoprotein, classified according to their functional and physical properties chylomicrons, very low density lipoproteins (VLDLs), intermediate density lipoproteins (IDLs), low density lipoproteins (LDLs), and high density lipoproteins (HDLs). The major function of lipoproteins is to transport triacylglycerols, cholesterol and phospholipids around the body. 

Blood plasma contains a number of soluble lipoproteins, which are classified, according to their densities, into four major types. These lipid-protein complexes function as a lipid transport system. Isolated lipids are insoluble in blood, but they are rendered soluble, and therefore transportable, by combination with specific proteins, the so-called lipoproteins. There are four basic types in human blood (1) chylomicrons, (2) very low density lipoproteins (VLDL), (3) low-density lipoproteins (LDL). and (4) high-density lipoproteins (HDL). Their properties are summarized in Table 6.2. 

Human lipoproteins exist in several sizes and densities with differing lipid to protein ratios. These various lipoproteins have different origins in the body, different destinations and different functions (10). Thus, chylomicrons are extremely large low density particles formed in the intestine and designed to deliver dietary fat to adipose tissue. Very low density lipoproteins (VLDL), on the other hand, are smaller, more dense particles designed to deliver lipids from the liver to adipose and other tissues. Low density lipoproteins (LDL), formed from VLDL or produced in the liver or intestine deliver cholesterol to peripheral tissue, while high density lipoproteins (HDL) function to return cholesterol from peripheral tissues to the liver for catabolism. There is a complex exchange of lipids and apoproteins between the lipoprotein classes. 

Chen LY, Mehta JL (1994) Inhibitory effect of high-density lipoprotein on platelet function is mediated by increase in nitric oxide Aase activity in platelets. LifeSci 23 1815-1821. 

Lipoproteins are assembled in two organs, the small intestine and the liver. The lipoproteins assembled in the intestine contain the lipids assimilated from the diet. These lipoproteins, called chylomicrons, leave the enterocyte and enter the bloodstream via the Lymphatic system. The lipoproteins assembled in the liver contain lipids originating from the bloodstream and from de novo synthesis in the liver. The term de novo simply means "newly made from simple components" as opposed to "acquired from the diet" or "recycled from preexisting complex components." These lipoproteins, called very-low-dcnslty lipoproteins (VLDLs), are secreted from the liver into the bloodstream. The liver also synthesizes and secretes other Lipoproteins called high-density Lipoproteins (HDLs), which interact with the chylomicrons and VLDLs in the bloodstream and promote their maturation and function. The data in Table 6-4 show that chylomicrons contain a small proportion of protein, whereas HDLs have a relatively high protein content. Of greater interest is the identity and function of the proteins that constitute these particles. These proteins confer specific properties to lipoprotein particles, as detailed later in this chapter. 

Gillotte, K., Davidson, W-, Lund-Katz, S., Rothblat, G, H and Phillips M. C, fl9%). Apolipoprotein A-I structural modification and the functionality of reconstituted high-density lipoprotein particles in cellular cholesterol efflux.. Biol. CItejn, 271, 23792-23798-... 

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