High-density lipoproteins apolipoproteins

Schaefer EJ, Blum CB, Levy RI, Jenkins LL, Alaupovic P, Foster DM, Brewer HB, Jr. Metabolism of high-density lipoprotein apolipoproteins in Tangier disease. N Engl J Med 1978 299 905-10. 

Oram JF, Mendez AJ, Slotte JP, et al. (1991) High density lipoprotein apolipoproteins mediate removal of sterol from intracellular pools but not from plasma membranes of cholesterol-loaded fibroblasts. Arterioscler Thromb 11 403 14... 

Kashyap ML, Srivastava LS, Hynd BA, Perisutti G, Brady DW, Gartside P, Glueck CJ (1978) The role of high density lipoprotein apolipoprotein C-II in triglyceride metabolism. Lipids 13 933-942... 

Abbtvviations apoC-lll, apolipoprotein C-lll apoA-l, apolipoprotein A-l apoA-ll, apolipoprotein A-ll CRP, C-reactive protein VLDL, very low density lipoprotein TG, triglycerides LDL-C, low density lipoprotein cholesterol HDL-C, high density lipoprotein cholesterol. 

Figure 25-3. Metabolic fate of chylomicrons. (A, apolipoprotein A B-48, apolipoprotein B-48 , apolipoprotein C E, apolipoprotein E HDL, high-density lipoprotein TG, triacylgiycerol C, cholesterol and cholesteryl ester P, phospholipid HL, hepatic lipase LRP, LDL receptor-reiated protein.) Only the predominant lipids are shown.

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Lorenzi, I, von Eckardstein, A, Cavelier, C, Radosavljevic, S, and Rohrer, L, 2008. Apolipoprotein A-I but not high-density lipoproteins are internalised by RAW macrophages Roles of ATP-binding cassette transporter A1 and scavenger receptor BI. JMolMed 86, 171-183. 

Contrary to LDL, high-density lipoproteins (HDL) prevent atherosclerosis, and therefore, their plasma levels inversely correlate with the risk of developing coronary artery disease. HDL antiatherogenic activity is apparently due to the removal of cholesterol from peripheral tissues and its transport to the liver for excretion. In addition, HDL acts as antioxidants, inhibiting copper- or endothelial cell-induced LDL oxidation [180], It was found that HDL lipids are oxidized easier than LDL lipids by peroxyl radicals [181]. HDL also protects LDL by the reduction of cholesteryl ester hydroperoxides to corresponding hydroperoxides. During this process, HDL specific methionine residues in apolipoproteins AI and All are oxidized [182]. 

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. 

K38. Kronenberg, F., Lobenstanz, E.-M., Konig, P., Utermann, G., and Dieplinger, H., Effect of sample storage on the measurement of lipoprotein(a), apolipoproteins B and A-IV, total and high density lipoprotein cholesterol and triglycerides. J. Lipid Res. 35, 1318-11328 (1994). 

Fig. 10.5 Apolipoprotein E (APOE)-relsled serum levels of APOE, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density hpoprotein (LDL) cholesterol, amyloid- 3 peptide (1 2), and histamine in Alzheimer s disease. (Adapted from refs. 12,59, and 289.)...

Lipoproteins are an important class of serum proteins in which a spherical hydrophobic core of triglycerides or cholesterol esters is surrounded by an amphipathic monolayer of phospholipids, cholesterol and apolipoproteins (fatbinding proteins). Lipoproteins transport lipid in the circulation and vary in size and density, depending on their proteindipid ratio (Figure 7.3). Lipoprotein metabolism is adversely affected by obesity low-density lipoprotein (LDL)-cholesterol and plasma triglyceride are increased, together with decreased high-density lipoprotein (HDL)-cholesterol concentrations. 

Cl. Camejo, G., Suarez, Z. M., and Munoz, V., The apolipoproteins of human plasma high density lipoprotein a study of their lipid-binding capacity and interaction with lipid monolayers. Biochim. Biophys. Acta 218, 155-166 (1970). 

Gallbladder effect. Seed oil, administered orally to 11 young normocholesterolemic males at a dose of 100 g/day, was active. The subjects received 3 weeks of a low-fat diet followed by 3 weeks of a diet enriched with 100 g/daily of olive oil. Mean total cholesterol, total apolipoprotein (apo) B, low-density lipoprotein (LDL) cholesterol, and triglycerides decreased significantly after the olive oil diet. High-density lipoprotein (HDL) cholesterol, apo A-1, cholesterol saturation of bile, and gallbladder volumes were unchanged . 

Choiesteryi Ester Transfer Protein inhibitors Cholesterol ester transfer protein (CETP) is a glycoprotein that transfers choiesteryi ester from HDL (high density lipoprotein) to proatherogenic apolipoproteins (LDL—(low density lipoprotein). Its inhibition has beneficial effects at the level of HDL cholesterol. SC-71952 and torcetrapib are highly fluorinated CETP inhibitors. SC-71952 is a disymmetrical sulfide with 10 fluorine atoms. Torcetrapib contains three CF3 groups (Figure 8.61). ... 

Fig. 5.2.1 The major metabolic pathways of the lipoprotein metabolism are shown. Chylomicrons (Chylo) are secreted from the intestine and are metabolized by lipoprotein lipase (LPL) before the remnants are taken up by the liver. The liver secretes very-low-density lipoproteins (VLDL) to distribute lipids to the periphery. These VLDL are hydrolyzed by LPL and hepatic lipase (HL) to result in intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), respectively, which then is cleared from the blood by the LDL receptor (LDLR). The liver and the intestine secrete apolipoprotein AI, which forms pre-jS-high-density lipoproteins (pre-jl-HDL) in blood. These pre-/ -HDL accept phospholipids and cholesterol from hepatic and peripheral cells through the activity of the ATP binding cassette transporter Al. Subsequent cholesterol esterification by lecithinxholesterol acyltransferase (LCAT) and transfer of phospholipids by phospholipid transfer protein (PLTP) transform the nascent discoidal high-density lipoproteins (HDL disc) into a spherical particle and increase the size to HDL2. For the elimination of cholesterol from HDL, two possible pathways exist (1) direct hepatic uptake of lipids through scavenger receptor B1 (SR-BI) and HL, and (2) cholesteryl ester transfer protein (CfiTP)-mediated transfer of cholesterol-esters from HDL2 to chylomicrons, and VLDL and hepatic uptake of the lipids via the LDLR pathway...

Funke H, Eckardstein A von, Pritchard PH, Karas M, Albers JJ, Assmann G (1991) A frame-shift mutation in the human apolipoprotein A-I gene causes high density lipoprotein deficiency, partial lecithin cholesterol-acyltransferase deficiency, and corneal opacities. J Clin Invest 87 371-376... 

Miccoli R, Zhu Y, Daum U, Wessling J, Huang Y, Navalesi R, Assmann G, Eckardstein A von (1997) A natural apolipoprotein A-I variant, apoA-I (L141R)Pisa, interferes with the formation of alpha-high density lipoproteins (HDL) but not with the formation of pre beta 1-HDL and influences efflux of cholesterol into plasma. J Lipid Res 38 1242-1253... 

Apolipoproteins ( apo designates the protein in its lipid-free form) combine with lipids to form several classes of lipoprotein particles, spherical complexes with hydrophobic lipids in the core and hydrophilic amino acid side chains at the surface (Fig. 21-39a). Different combinations of lipids and proteins produce particles of different densities, ranging from chylomicrons to high-density lipoproteins. These particles can be separated by ultracentrifugation (Table 21-2) and visualized by electron microscopy (Fig. 21-39b). 

The fourth major lipoprotein type, high-density lipoprotein (HDL), originates in the liver and small intestine as small, protein-rich particles that contain relatively little cholesterol and no cholesteryl esters (Fig. 21-40). HDLs contain apoA-I, apoC-I, apoC-II, and other apolipoproteins (Table 21-3), as well as the enzyme lecithin-cholesterol acyl transferase (LCAT), which catalyzes the formation of cholesteryl esters from lecithin (phosphatidylcholine) and cholesterol (Fig. 21-41). LCAT on the surface of nascent (newly forming) HDL particles converts the cholesterol and phosphatidylcholine of chylomicron and VLDL remnants to cholesteryl esters, which begin to form a core, transforming the disk-shaped nascent HDL to a mature, spherical HDL particle. This cholesterol-rich lipoprotein then returns to the liver, where the cholesterol is unloaded some of this cholesterol is converted to bile salts. 

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... 

The small particles of plasma lipoprotein, which carry triacylglycerols, can be separated according to their buoyant densities by centrifugation. They have been classified into five groups of increasing density but smaller size as chylomicrons, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density (LDL), and high density lipoproteins (HDL) (Table 21-1 and Fig. 21-2). Each lipoprotein particle contains one or more apolipoproteins (Table 21-2), whose sizes vary from the enormous 4536-residue apoB-100 to apoC-II and apoC-III, each of which contains just 79 residues73 and the 57-residue apoC-I.7b... 

In 147 postmenopausal women with early breast cancer who took exemestane in a placebo-controlled study, exemestane caused modest reductions in high-density lipoprotein cholesterol and apolipoprotein, but had no major effect on lipid profile, homocysteine concentrations, or coagulation (14). 

A 64-year-old woman who had taken metformin for 3 years had a high-density lipoprotein concentration of 1.2 mmol/1, which fell to 0.26 mmol/1 when she took rosiglitazone. The HbAic fell from 10.1% to 7.9%. Fenofibrate was added and the HDL concentration fell further to 0.11 mmol/1. Triglycerides, 2.7 mmol/1 before treatment, increased to 4.7 mmol/1. Apolipoprotein A1 concentrations were low at 0.14 g/ 1 (reference range 1.1-2.05 g/1). On withdrawing both the rosiglitazone and the fenofibrate the HDL concentration rose to 0.95 mmol/1. 

Phenytoin increases high-density lipoprotein (HDL) cholesterol (118), and may also increase total cholesterol and serum triglyceride concentrations (SED-13,143) (119). In a 5-year prospective study with carbamazepine, there was a persistent rise in total cholesterol and HDL cholesterol, whereas triglycerides and low-density lipoprotein (LDL) cholesterol increased only transiently (120). In a more recent study, total cholesterol fell when 12 patients were switched from carbamazepine to oxcarbazepine, but HDL cholesterol and triglycerides were unchanged (121). In a comparison of 101 epileptic patients with matched controls, valproate was associated with lower total and LDL cholesterol, whereas carbamazepine was associated with higher HDL cholesterol and apolipoprotein A concentrations and phenobarbital with higher concentrations of total and HDL cholesterol and apolipoproteins A and B. The ratio of total to HDL cholesterol was reduced with valproate and carbamazepine but not with phenobarbital (122). 

Bergt C, Fu X, Huq NP, Kao J, Heinecke JW (2004) Lysine Residues Direct the Chlorination of Tyrosines in YXXK Motifs of Apolipoprotein A-I When Hypochlorous Acid Oxidizes High Density Lipoprotein. J Biol Chem 279 7856... 

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