High-density lipoproteins metabolism

Quig, D. W., and D. B. Zilversmit. High-density lipoprotein metabolism in a rabbit model of hyperalphalipo-proteinemia. Atherosclerosis 1989 76(1) 9-19. 

Breslow JL. Familial disorders of high-density lipoprotein metabolism. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Diseases, Vol. II. 7th ed. New York McGraw-Hill, 1995 2031-52. 

Shelness, G.S. and Rudel, L.L. (2005) A role for the pregnane X receptor in high-density lipoprotein metabolism. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 2016-2017. 

Ordovas JM, Corella D, Demissie S, et al.. Dietary fat intake determines the effect of a common polymorphism in the hepatic lipase gene promoter on high-density lipoprotein metabolism evidence of a strong dose effect in this gene-nutrient interaction in the Framingham Study, Circulation, Oct 29 2002 106(18) 2315-2321. 

Albers JJ, Wahl PW, Cabana GV, Hazzard WR, Hoover JJ (1976) Quantitation of apolipoprotein A-I of human plasma high density lipoprotein. Metabolism 25 633-644... 

Fruchart JC. Peroxisome proliferators-activated receptor-a activation and high-density lipoprotein metabolism. Am J Cardiol 2001 88 24N-29N. 

Tall, A.R. (1990) Plasma high density lipoproteins. Metabolism and relationship to atherogenesis. J. Clin. Invest., 86, 379-384. 

M.A. Dillingham, Bile sequestrant therapy alters the composition of low density and high density lipoproteins. Metabolism 28 221 (1979). 

Chylomicron and high density lipoprotein metabolism Endotoxemia, inflammation, vascular function, and postprandial lipid metabolism in patients with type 1 diabetes 178... 

Heterogeneous reaction (Section 6 1) A reaction involving two or more substances present in different phases Hydro genation of alkenes is a heterogeneous reaction that takes place on the surface of an insoluble metal catalyst Heterolytic cleavage (Section 4 16) Dissociation of a two electron covalent bond in such a way that both electrons are retained by one of the initially bonded atoms Hexose (Section 25 4) A carbohydrate with six carbon atoms High density lipoprotein (HDL) (Section 26 11) A protein that carries cholesterol from the tissues to the liver where it is metabolized HDL is often called good cholesterol Histones (Section 28 9) Proteins that are associated with DNA in nucleosomes... 

High-density lipoprotein (HDL) (Section 26.11) Aprotein that carries cholesterol from the tissues to the liver where it is metabolized. HDL is often called good 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.

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

Patients with metabolic syndrome have an additional lipid parameter that needs to be assessed, namely non-high-density lipoprotein (non-HDL) cholesterol (total cholesterol minus HDL cholesterol). The target for non-HDL cholesterol is less than the patient s LDL cholesterol target plus 30 mg/dL (0.78 mmol/L). 

Metformin also has been shown to produce beneficial effects on serum lipid levels and thus has become a first-line agent for type 2 DM patients with metabolic syndrome. Triglyceride and low-density lipoprotein (LDL) cholesterol levels often are reduced by 8% to 15%, whereas high-density lipoprotein (HDL) cholesterol improves by approximately 2%. A modest weight loss of 2 to 3 kg (4.4—6.6 lb) also has been reported with metformin therapy. Metformin often is used in combination with a sulfonylurea or a thiazolidinedione for synergistic effects. 

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. 

Chiesa G, Michelagnoli S, Cassinotti M, Gianfranceschi G, Werba JP, Paz-zucconi F, et al. Mechanisms of high-density lipoprotein reduction after probu-col treatment changes in plasma cholesterol esterification/transfer and lipase activities. Metabolism 1993 42 229-235. 

Further research on serum cholesterol revealed that is exists in two forms, high and low density lipoprotein. The high density lipoprotein appears to consist of cholesterol that is being moved to the liver for metabolism while low density lipoprotein appears to be cholesterol that is likely to block arteries. This has led to the labelling of high density lipoprotein as good cholesterol and of low density lipoprotein as bad cholesterol. 

Details of plasma lipoproteins and their metabolism are given in Section 5.5. Most of the cholesterol in the blood is carried as part of low density lipoprotein (LDL) or high density lipoprotein (HDL), whereas most triglyceride, in the fasting state, is carried by very low density lipoprotein (VLDL). The relative concentrations of these lipoproteins constitute the lipid profile and determine CVD risk. Diabetics are more likely to show an unhealthy profile with elevated concentrations of LDL and triglyceride but reduced HDL concentration. This pattern can be partly explained by enhanced fatty acid liberation from adipocytes as a consequence of insulin resistance in that tissue and due to reduced removal from the circulation of triglycerides, which is also insulin dependent. 

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. 

However, unlike atherogenic low-density lipoproteins and very low-density lipoproteins, which when metabolized release cholesterol that is in the form of esters and is deposited in tissue, chylomicrons and high-density lipoproteins are not atherogenic. There is a direct link between the concentration of high-density lipoproteins in blood plasma and expressed atherosclerotic changes in medium and large arteries. 

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