Lipoprotein composition and

CN208 Castillo, M., J. H. Hortal, E. Garcia-Fuentes, M. F. Zafra, and E. Garcia-Peregrin. Coconut oil affects lipoprotein composition and structure of neonatal chicks. J Biochem (Tokyo) 1996 119(4) 610-616. 

Yang CY, Gu ZW, Xie YH, et al. Effects of gemfibrozil on very-low-density lipoprotein composition and low-density lipoprotein size in patients with hypertriglyceridemia or combined hyperlipidemia. Atherosclerosis 1996 126 105—116. 

C, Preliminary Relationships Observed between Lipoprotein Concentration, Lipoprotein Composition, and Other Parameters... 

Table III Serum Lipid, Lipoprotein Composition, and Lipoprotein Correlation Coefficients (35-49-Year Males, 16 Cases)... 

Plasma lipid transfer proteins, which include the cholesteryl-ester-transfer-protein (CETP previously known as lipid transfer protein I, LTP-I) and the phospholipid-transfer-protein (PLTP previously known as lipid transfer protein II, LTP-II) mediate the transfer of lipids (cholesteryl esters, triglycerides and phospholipids) between lipoproteins present in human plasma. These proteins significantly affect plasma lipoprotein concentration and composition. 

Oncley, J.L., Gurd, F.R.N. and Melin, M. (1950). Preparation and properties of serum and plasma proteins XXV. Composition and properties on human serum d-lipoprotein. J. Am. Chem. Soc. 72, 458-464. 

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. 

Trautwein, E. A., Rieckhoff, D., Kunath-Rau, A., and Erbersdobler, H. F. (1998). Psyllium, not pectin or guar gum, alters lipoprotein and biliary bile acid composition and fecal sterol excretion in the hamster. Lipids 33, 573-582. 

One of the most striking lipoprotein abnormalities of familial LCAT deficiency is the presence in the LDL fraction of abnormally large particles, containing variable but unusually great proportions of unesteri-fied cholesterol and lecithin (F6, G14, N5). Recently, an abnormal LDL lipoprotein, identical to cholestatic lipoprotein, LP-X (see Section 8.1) was demonstrated in plasma from patients with familial LCAT deficiency (Ml, T2). Identity of the abnormal LDL lipoprotein and LP-X was shown by electron microscopy, composition, and immunological techniques (T2). The amount of LP-X in plasma of patients with obstructive jaundice ranged from 40 to 1200 mg/100 ml (M3) whereas plasma from patients with familial LCAT deficiency contained 49 to 152 mg/100 ml (T2). 

G13. Glomset, J. A., Norum, K. R., and King, W., Plasma lipoproteins in familial lecithin cholesterol acyltransferase deficiency lipid composition and reactivity in vitro. J. Clin. Invest. 49, 1827-1837 (1970). 

K6. Kostner, G., and Alaupovic, P., Studies of the composition and structure of plasma lipoproteins. C- and N-terminal amino acids of the two nonidentical polypeptides of human plasma apolipoprotein A. FEBS (Fed. Eur. Biochem. Soc.), Lett. 15, 320-324 (1971). 

Mills, G. L., Seidel, D., and Alaupovic, P., Ultracentrifugal characterization of a lipoprotein occurring in obstructive jaundice. Clin. Chem. Acta 26, 239-244 (1969). Nelson, G., ed., Blood Lipids and Lipoproteins Quantification, Composition and Metabolism, 980 pp. Wiley (Interscience), New York, 1972. 

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. 

Alterations in the composition of the plasma lipids caused by estrogens are characterized by an increase in the high-density lipoproteins (HDL), a slight reduction in the low-density lipoproteins (LDL), and a reduction in total plasma cholesterol levels. Plasma triglyceride levels are increased. Estrogens decrease hepatic oxidation of adipose tissue lipid to ketones and increase synthesis of triglycerides. 

Each class of lipoprotein has a specific function, determined by its point of synthesis, lipid composition, and apolipoprotein content. At least nine different apolipoproteins are found in the lipoproteins of human plasma (Table 21-3), distinguishable by their size, their reactions with specific antibodies, and their characteristic distribution in the lipoprotein classes. These protein components act as signals, targeting lipoproteins to specific tissues or activating enzymes that act on the lipoproteins. 

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). 

Between these two classes, in both size and composition, are the cholesteryl ester-rich low-density lipoproteins (LDLs), the intermediate-density lipoproteins (IDLs), and the triacylglycerol-rich very-low-density lipoproteins (VLDLs). 

Bielmann P, Leduc G, Jequier JC, et al. Changes in the lipoprotein composition after chronic administration of metoprolol and propranolol in hypertriglyceridemic-hypertensive subjects. Curr Ther Res 1981 30 956. 

Gottfried, E.L. (Nelson, G.J., ed.) "Blood Lipids and Lipoproteins Quantitation, Composition and Metabolism , Wiley-Interscience, New York, 1972, 387-415. 

Jimenez, M.A., Scarino, M.L., Vignolini, F., and Mengheri, E. 1990. Evidence that polyunsaturated lecithin induces a reduction in plasma cholesterol level and favorable changes in lipoprotein composition in hypercholesterolemic rats. J. Nutr. 120, 659-667. 

Alterations to both the total concentration of lipoproteins in plasma and the lipid composition of lipoproteins will therefore likely affect the pattern of drug lipoprotein binding and potentially both pharmacokinetic and pharmacodynamic drug end points. 

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