Lipoproteins apoproteins

Fio. 1. Fraction of human serum liigh-density lipoprotein apoprotein (apo HDD, scheme 1. As in scheme 2, the method makes use of the combination of gel filtration and ion-exchange chromatography. Fraction IV is obtained in its dimer form. 

Fig. 4. Amino add sequence of human serum high-density lipoprotein apoprotein (apo HDL), fraction IV (dimer). Data from Brewer et al. (B5).

Research on plasma lipoproteins has entered a highly productive period during which major advances have been made from both the conceptual and technological standpoints. The information gained on lipoprotein apoproteins has particular relevance, especially in terms of pri-... 

Scanu, A. M., Binding of human serum high density lipoprotein apoprotein with aqueous dispersions of phospholipids. J. Biol. Chem. 242, 711-719 (1967). 

Knopp RH. Review of the effects of fenofibrate on lipoproteins, apoproteins, and bile saturation US studies. Cardiology 1989 76(Suppl l) 14-22. 

Calvert, G.D., Abbey, M. Plasma lipoproteins apoproteins and proteins concerned with lipid metabohsm. Adv. Clrn. Chem. 1985 24 218-298... 

See also Table 18.2, Lipoproteins, Apoproteins, HDLs, LCAT, Chylomicrons... 

Levy, R. 1981. Cholesterol, lipoproteins, apoproteins, and heart disease. Clinical Chemistry 27 653-662. 

Huff, M.W. P.M. Giovannetti B.M. Wolfe. Turnover of very low-density lipoprotein-apoprotein B is increased by substitution of soybean protein for meat and dairy protein in the diets of hypercholesterolemic men. Am. J. Clin. Nutr. 1984, 39, 888—897. 

Apart from their operational distinction on the basis of density and lipid composition the plasma lipoprotein classes are also distinguished by the nature of the polypeptides present. The apoprotein species have been characterized and designated family names from A to H. The human plasma lipoprotein apoprotein distribution is shown in Table 12.3. Although the distribution, interchange and metabolism of lipoprotein apoproteins is extremely complicated some overall aspects of the dynamic situation can be discerned (see Schaefer etal, 1978). For example, the apoprotein content of newly synthesized VLDL and chylomicrons changes drastically as these lipoproteins enter the circulation and interact with the other lipoproteins present. Both... 

P36 Pottenger, L. A., Frazier, L. E., Dubien, L. H., Getz, G. S. and Wissler, R. W. Carbohydrate composition of lipoprotein apoproteins isolated from rat plasma and from the livers of rats fed orotic acid. Biochem. Biophys. Res. Commun. 54, 770-776 (1973)... 

Schaefer EJ, Eisenberg S, Levy RI (1978) Lipoprotein apoprotein metabolism. J Lipid Res 19 667-687... 

The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules (Figure 25-1). These are oriented so that their polar groups face outward to the aqueous medium, as in the cell membrane (Chapter 14). The protein moiety of a lipoprotein is known as an apo-lipoprotein or apoprotein, constituting nearly 70% of some HDL and as litde as 1% of chylomicrons. Some apolipoproteins are integral and cannot be removed, whereas others are free to transfer to other hpoproteins. 

As an example, the low-density lipoprotein (LDL) molecule and its receptor (Chapter 25) are internalized by means of coated pits containing the LDL receptor. These endocytotic vesicles containing LDL and its receptor fuse to lysosomes in the cell. The receptor is released and recycled back to the cell surface membrane, but the apoprotein of LDL is degraded and the choles-teryl esters metabolized. Synthesis of the LDL receptor is regulated by secondary or tertiary consequences of pinocytosis, eg, by metabolic products—such as choles-... 

Becker, N., Illingsworth, R., Alaupovic, P., Connor, W. E., Sundberg, E. E., Effects of saturated, monounsaturated, and w-6 polyunsaturated fatty acids on plasma lipids, lipoproteins and apoproteins in humans, Am J Clin Nutr, 37, 355, 1983... 

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. 

The liver plays a decisive role in the cholesterol metabolism. The liver accounts for 90% of the overall endogenic cholesterol and its esters the liver is also impli-cated in the biliary secretion of cholesterol and in the distribution of cholesterol among other organs, since the liver is responsible for the synthesis of apoproteins for pre-p-lipoproteins, a-lipoproteins, and P-lipoproteins which transport the secreted cholesterol in the blood. In part, cholesterol is decomposed by intestinal micro-flora however, its major part is reduced to coprostanol and cholestanol which, together with a small amount of nonconverted cholesterol, are excreted in the feces. 

In adult brain most cholesterol synthesis occurs in astrocytes. Apoprotein E (apoE) is the major apolipopro-tein of the CNS and it is secreted by astrocytes. In astrocyte cultures apoE appears in the media as cholesterol-rich particles of a size similar to peripheral HDL (5-12 nm) (Fig. 2-7). The ATP-dependent transporter ABCA1, expressed by both astrocytes and neurons, promotes the formation of the apoE-stabilized high-density lipoprotein (HDL)-sized particles from astrocytic cholesterol. 

Although most assays perform well with regard to specificity and reproducibility, the major problem remains their standardization (A9, Dl, K30, L4). There is currently no internationally accepted standard, and the selection of a reference material raised many problems (A8, G5, K30, L4). A number of questions have not been solved Should the standard consist of several apo(a) isoforms Can the reference material be lyophilized Should results be expressed as mass or as moles of apoprotein or lipoprotein How should the protein mass of the primary standard be determined What are optimal storage conditions for the secondary standard Which method can be used as a reference method Can recombinant apo(a) represent an alternative for a primary standard These problems came to light in the course of the international surveys whose results were presented at the Lp(a) Workshop in New Orleans (1992) (L4). 

Lipoproteins (Table 5.2) are macromolecular aggregates with varying proportions of triglycerides and cholesterol (with some phosphoacylglycerols) and apoproteins. The apoproteins act as recognition flags for receptor binding, for example apo B and apo E,... 

Lipoprotein class Lipid components Main apoprotein components Enzymes present Role... 

Many of the globulins act as transport proteins. Of particular interest are those proteins which are combined with lipids, themselves synthesized in the liver, to form lipoprotein complexes. High density lipoprotein (HDL), which contains predominantly apoproteins A and C combined with mainly phospholipids (most of the cholesterol found in mature HDL is added later) and very low density lipoprotein... 

Very low density lipoprotein is not the only lipoprotein to be secreted by the liver. HDL is released into the blood as a nascent (immature) discoid particle. As the HDL circulates within the circulation, it matures by exchanging apoproteins and lipid components with other lipoproteins and cells. Mature spherical HDL is... 

Lipoprotein (a) (abbreviated to Lp(a)) is a complex between LDL and apoprotein (a) that forms spontaneously in blood. Lp(a) is secreted by the liver but its function is unknown. A high plasma level of Lp(a) interferes with the conversion of plasminogen to plasmin, the role of which is to break down blood clots and even disperse small clots. 

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. 

The HDLs also originate in the liver. They return the excess cholesterol formed in the tissues to the liver. While it is being transported, cholesterol is acylated by lecithin cholesterol acyltransferase (LCAT). The cholesterol esters formed are no longer amphipathic and can be transported in the core of the lipoproteins. In addition, HDLs promote chylomicron and VLDL turnover by exchanging lipids and apoproteins with them (see above). 

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